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Interferon and Ribavirin Second-Line Option for Hepatitis C
By Crystal Phend, Staff Writer, MedPage Today
Published: June 02, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
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SAN FRANCISCO, June 2 -- Some hepatitis C patients who don't respond to standard therapy may get a second chance at eradication with daily interferon alfacon-1 (Infergen) plus ribavirin.
Action Points
■Note that the study was not powered to make comparisons between dose groups.
So found Bruce R. Bacon, M.D., of Saint Louis University, and colleagues in the randomized Daily-Dose Consensus Interferon and Ribavirin: Efficacy of Combined Therapy (DIRECT) clinical trial.
Among participants who failed initial treatment with pegylated interferon plus ribavirin, retreatment with the interferon alfacon-1 combination yielded sustained virologic response in 6.9% among the 9-µg dose group and 10.7% in the 15-µg dose group.
The response rates were particularly promising -- up to 31.6% -- in interferon-sensitive patients with low baseline liver fibrosis scores, the researchers reported in the June issue of Hepatology.
This strategy "can be considered for select patients with chronic hepatitis C virus who have failed to respond to prior treatment with pegylated interferon and ribavirin," they wrote.
Roughly half of patients with chronic hepatitis C fail to respond to their first course of the standard combination of pegylated interferon and ribavirin, the researchers noted.
No standard has yet emerged for second-line therapy, since simply repeating the same treatment yields response rates under 10%, they said.
"Some clinicians have used the 'watchful waiting' approach and are anticipating new antiviral therapies with either protease inhibitors or polymerase inhibitors," they wrote.
Others have tried switching pegylated interferon brands, extending the drug's duration, increasing doses, or maintenance dosing, they added.
The DIRECT trial, a registry trial for the combination in second-line therapy, tested high doses of daily consensus interferon in 487 nonresponders.
Interferon alfacon-1 is also known as consensus interferon because it is a recombinant molecule synthesized to contain the most common amino acids from various types of naturally occurring interferon alfa.
Participants were randomized for the first 24 weeks to no treatment or either 9 or 15 µg of subcutaneous interferon alfacon-1 per day, with 1,000 to 1,200 mg of oral ribavirin per day, depending on body weight.
After that period, control group patients were offered randomization to one of the two treatment dose groups.
Pooling the end-of-treatment results for these two phases of the trial, intent-to-treat analysis revealed virologic response in 14.7% of the 9-µg consensus interferon dose group and 18.5% in the 15 µg arm, followed by lower rates of sustained virologic response (defined as undetectable viral levels at least 24 weeks after treatment).
Pooled relapse rates were 52% and 42% among these responders, respectively.
Although the researchers warned that the study was not statistically powered to compare the dose groups, they noted that post hoc analysis revealed no difference in sustained virologic rates between the two (P=0.141).
While control group patients went untreated, none achieved sustained virologic response.
The best sustained virologic response rates were seen in patients with:
•A partial virologic response to their prior course of pegylated interferon treatment, with at least a 2-log10 reduction in hepatitis C viral RNA (11% in the 9-µg group and 23% in the 15-µg group)
•Noncirrhotic patients with fibrosis scores of F0 to F3 at baseline (7.8% and 13.1%, respectively)
•Both interferon sensitivity and low fibrosis scores (10.7% and 31.6%, respectively)
Patients with cirrhosis did not appear to benefit from retreatment with consensus interferon and ribavirin unless they had at least a 1-log drop in viral levels on prior therapy, Dr. Bacon's group noted.
The researchers did not report number needed to treat and could not be contacted in time for publication.
But the consensus interferon-ribavirin combination appeared safe and well-tolerated for second-line therapy, they said.
The study was sponsored by InterMune and Valeant Pharmaceuticals International with additional support for the study publication from Three Rivers Pharmaceuticals.
Dr. Bacon reported conflicts of interest with Three Rivers, Roche, Bristol-Myers Squibb, Schering-Plough, Coley Pharmaceuticals, ISIS, Valeant, and GlaxoSmithKline.
Co-authors reported conflicts of interest for Schering-Plough, Roche, Three Rivers, Idenix, Valeant, Gilead Sciences, Biotex, and Vertex.
Primary source: Hepatology
Source reference:
Bacon BR, et al "Retreating chronic hepatitis c with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results" Hepatology 2009; 49: 1838-46.
Related Article(s):
•AASLD: Consensus Interferon Plus Ribavirin Gives HCV Patients Second Chance
•DDW: Relapsed HCV Patients Achieve Sustained Response with 72-Week Treatment
Thursday, June 4, 2009
CDC Surveillance for Acute Viral Hepatitis --- United States, 2007
CDC
Surveillance for Acute Viral Hepatitis --- United States, 2007
Danni Daniels, MS
Scott Grytdal, MPH
Annemarie Wasley, ScD
Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC
Corresponding author: Danni Daniels, MS, Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC, 1600 Clifton Rd., N.E., MS G-37, Atlanta, GA 30333. Telephone: 404-718-8596; Fax: 404-718-8585. E-mail: dld4@cdc.gov.
Abstract
Problem: In the United States, acute viral hepatitis most frequently is caused by infection with any of three distinct viruses: hepatitis A virus (HAV), hepatitis B virus (HBV), or hepatitis C virus (HCV). These unrelated viruses are transmitted through different routes and have different epidemiologic profiles. Safe and effective vaccines have been available for hepatitis B since 1981 and for hepatitis A since 1995. No vaccine exists against hepatitis C. HBV and HCV can persist as chronic infections and represent a leading cause of chronic liver disease and hepatocellular carcinoma in the United States.
Reporting Period Covered: Cases in 2007, the most recent year for which data are available, are compared with those from previous years.
Description of System: Cases of acute viral hepatitis are reported voluntarily to CDC by state and territorial health departments via CDC's National Notifiable Disease Surveillance System (NNDSS). Reports are received electronically via CDC's National Electronic Telecommunications System for Surveillance (NETSS).
Results: Acute hepatitis A incidence has declined 92%, from 12.0 cases per 100,000 population in 1995 to 1.0 case per 100,000 population in 2007, the lowest rate ever recorded. Declines were greatest among children and in those states where routine vaccination of children was recommended beginning in 1999. Acute hepatitis B incidence has declined 82%, from 8.5 cases per 100,000 population in 1990 to 1.5 cases per 100,000 population in 2007, the lowest rate ever recorded. Declines occurred among all age groups but were greatest among children aged <15 years. Following a peak in 1992, incidence of acute hepatitis C declined; however, since 2003, rates have plateaued. In 2007, as in previous years, the majority of these cases occurred among adults, and injection-drug use was the most common risk factor.
Interpretation: The results documented in this report suggest that implementation of the 1999 recommendations for routine childhood hepatitis A vaccination in areas of the United States with consistently elevated hepatitis A rates has reduced rates of infection. In addition, universal vaccination of children against hepatitis B beginning in 1991 has reduced disease incidence substantially among younger age groups. Higher rates of hepatitis B continue among adults, particularly among males aged 30--44 years, reflecting the need to vaccinate adults at risk for HBV infection. The decline in hepatitis C incidence after 1992 was attributable primarily to a decrease in incidence among injection-drug users. The reasons for this decrease were unknown but probably reflected changes in behavior and practices among injection-drug users.
Public Health Actions: The expansion in 2006 of recommendations for routine hepatitis A vaccination to include all children in the United States aged 12--23 months is expected to reduce hepatitis A rates further. Ongoing hepatitis B vaccination programs ultimately will eliminate domestic HBV transmission, and increased vaccination of adults with risk factors will accelerate progress toward elimination. Further prevention of hepatitis B and hepatitis C relies on identifying and preventing transmission of HBV or HCV in hospital and nonhospital health-care associated settings. In addition, prevention of hepatitis C relies on identifying and counseling uninfected persons at risk for hepatitis C (e.g., injection-drug users) regarding ways they can protect themselves from infection. Public health management of persons with chronic HBV or HCV infection will help to interrupt the transmission to susceptible persons, and their medical management will help to reduce the development of the sequelae from chronic liver disease.
Introduction
Viral hepatitis is caused by infection with any of at least five distinct viruses, of which the three most commonly identified in the United States are hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV). All three of these unrelated viruses can produce an acute illness characterized by nausea, malaise, abdominal pain, and jaundice. HBV and HCV also can produce a chronic infection that is associated with an increased risk for chronic liver disease and hepatocellular carcinoma.
This report describes the burden of acute disease attributed to infection with HAV, HBV, and HCV and describes acute disease trends in recent years. These data can be used to develop and evaluate prevention strategies and to identify persons in need of postexposure prophylaxis. The data on acute illness presented in this report do not include the burden of disease caused by chronic infection with HBV or HCV, both of which remain a substantial public health problem.
Hepatitis A Virus
HAV is transmitted through the fecal-oral route, spreading primarily through close personal contact. During 1987--1997, an average of 28,000 cases of hepatitis A occurred per year in the United States (range: 23,112--35,821), making hepatitis A one of the country's most frequently reported notifiable diseases. However, effective vaccines to prevent hepatitis A virus infection have been available in the United States since 1995. These vaccines have provided public health authorities with the opportunity to reduce disease incidence in the United States substantially and potentially to eliminate indigenous transmission.
In 1996, CDC's Advisory Committee on Immunization Practices (ACIP) recommended administration of hepatitis A vaccine for persons at increased risk, including international travelers, men who have sex with men (MSM), injection- and noninjection-drug users, and children living in communities with high rates of disease (1). In 1999, ACIP also recommended that routine vaccination be implemented for children living in 11 states with average hepatitis A rates during 1987--1997 of ≥20 cases per 100,000 population and also be considered for children in six states with rates of 10--20 cases per 100,000 population (2). In 2006, ACIP expanded these recommendations to include routine vaccination of children in all 50 states (3).
Hepatitis B Virus
HBV is transmitted by percutaneous or mucosal exposure to the blood or body fluids of an infected person, most often through injection-drug use (IDU), sexual contact with an infected person, or contact from an infected mother to her infant during delivery. Transmission of HBV also can occur in settings involving nonsexual interpersonal contact for an extended period (e.g., among household contacts of a person with chronic HBV infection). In 1991, a comprehensive strategy was recommended for the elimination of HBV transmission in the United States (4,5). The four elements of this strategy are 1) universal vaccination of infants beginning at birth, 2) prevention of perinatal HBV infection through routine screening of all pregnant women for HBV infection and the provision of immunoprophylaxis to infants born to infected women or to women of unknown infection status, 3) routine vaccination of previously unvaccinated children and adolescents, and 4) vaccination of adults at increased risk for infection (including health-care workers, dialysis patients, household contacts and sex partners of persons with chronic HBV infection, recipients of certain blood products, persons with a recent history of multiple sex partners or a sexually transmitted disease, MSM, and injection-drug users).
Hepatitis C Virus
HCV is transmitted primarily through percutaneous exposure; however, transmission can occur through unapparent percutaneous or mucosal exposures (e.g., persons with evidence of high-risk sexual practices). With an estimated 3.2 million chronically infected persons nationwide, HCV infection is the most common bloodborne infection in the United States (6). No vaccine against HCV infection exists. National recommendations for prevention and control of HCV infection (7), issued in 1998, emphasize primary prevention activities to reduce the risk for HCV transmission. These activities include screening and testing of blood donors, viral inactivation of plasma-derived products, risk-reduction counseling and screening of persons at risk for HCV infection, and routine practice of infection control in health-care settings.
Methods
Conditions for Which Surveillance is Conducted
National surveillance is conducted for acute hepatitis A, B, and C. The case definitions for these conditions are approved by the Council of State and Territorial Epidemiologists (CSTE) and are provided (see Case Definitions for Acute Viral Hepatitis).
Data Sources
Cases of acute viral hepatitis are reported to CDC weekly by state and territorial health departments to CDC's National Notifiable Diseases Surveillance System (NNDSS). Since January 1, 2002, all reports have been submitted electronically to CDC via the National Electronic Telecommunications System for Surveillance (NETSS).
States' participation in reporting nationally notifiable diseases, including acute viral hepatitis, is voluntary. All states collect and report basic information (e.g., event date, source of report, and demographic characteristics) regarding cases of acute viral hepatitis that are identified in their states. States also are asked to report additional information (e.g., laboratory test results, clinical information, and exposure history) regarding investigated cases, but completeness of reporting of these additional data varies. Information regarding state-specific reporting profiles for risk factor information is provided in this report (Table 1).
Case Definitions for Acute Viral Hepatitis
In 2007, cases were required to meet the clinical definition for acute hepatitis and virus-specific laboratory criteria for diagnosis specified in the following CSTE-approved case definitions (available at http://www.cdc.gov/ncphi/disss/nndss/casedef/case_definitions.htm#h).
Clinical Case Definition
Acute hepatitis was defined as acute illness with 1) discrete onset of symptoms (e.g., nausea, anorexia, fever, malaise, or abdominal pain) and 2) jaundice or elevated serum aminotransferase levels. For acute hepatitis C, elevated serum aminotransferase levels are specified as serum alanine aminotransferase levels of >400 IU/L.
Laboratory Criteria for Diagnosis of Hepatitis
Because the clinical characteristics are the same for all types of acute viral hepatitis, laboratory testing is needed to identify the specific viral cause of illness. The laboratory criteria for confirming each type of acute viral hepatitis are as follows:
•Acute hepatitis A
-- Immunoglobulin M (IgM) antibody to hepatitis A virus (anti-HAV) positive
•Acute hepatitis B
-- IgM antibody to hepatitis B core antigen (anti-HBc) positive or hepatitis B surface antigen (HBsAg) positive, and
-- IgM anti-HAV negative (if performed)
•Acute hepatitis C
-- IgM anti-HAV negative, and
-- IgM anti-HBc negative, and
--One of the following:
•Antibody to hepatitis C virus (anti-HCV) screening-test-positive with a signal to cut-off ratio predictive of a true positive for the particular assay as defined by CDC (signal to cut-off rations available at http:/www.cdc.gov/hepatitis/HCV/LabTesting.htm#section1),
OR
•Hepatitis C virus recombinant immunoblot assay (HCV RIBA) positive,
OR
•Nucleic acid test (NAT) for HCV RNA positive.
Case Classification
For this analysis, a confirmed case was one if it met the clinical case definition and was laboratory-confirmed. For hepatitis A, a case also was considered confirmed that met the clinical case definition and was diagnosed in a person who had an epidemiologic link to a person who had laboratory-confirmed hepatitis A (i.e., household or sexual contact with an infected person during the 15--50 days before the onset of symptoms).
Analyses
Incidence Calculations
For this report, crude rates per 100,000 population were calculated using Bureau of the Census estimates of the U.S. resident population in 2007. The following U.S. geographic regions were used: Midwest, Northeast, South, and West.*
Frequency Analysis
For this analysis, the percentage of persons who reported a specific risk factor was determined by using the number of cases reporting any information, positive or negative, regarding that exposure as the denominator. Depending on the type of hepatitis, the percentage of case reports that included any risk factor information ranged from 48%--50%. Multiple risk factors may be reported for a single person. Consequently, the percentages of persons with specific risk factors might total >100%.
Estimation Calculation
The estimation procedure for the number of new cases of acute hepatitis A begins with the number of acute hepatitis A cases reported voluntarily to CDC via CDC's NNDSS. The overall procedure makes two adjustments to the reported number of acute hepatitis A cases: one adjustment accounts for underreporting of cases to the passive surveillance system, and the other adjustment accounts for anicteric infections assumed not to have been recognized or reported. The result of these adjustments yields the estimated number of new cases of acute hepatitis A. The procedure for estimating the number of new cases of acute hepatitis B and acute hepatitis C is similar to that for acute hepatitis A (8).
Results
Acute Hepatitis A
Overall Incidence
Historically, acute hepatitis A rates have varied cyclically, with nationwide increases every 10--15 years. The national rate of hepatitis A has declined steadily since the last peak in 1995. In 2007, a total of 2,979 acute symptomatic cases of hepatitis A were reported; the national incidence (1.0 case per 100,000 population) was the lowest ever recorded (Figure 1; Tables 2 and 3). After asymptomatic infection and underreporting were taken into account, an estimated 25,000 new infections occurred in 2007 (8).
Rates by Region
In addition to temporal variation, historically, hepatitis A rates have varied geographically, with higher rates reported in the western region of the United States. However, incidence in the West declined substantially, most notably after issuance in 1999 of recommendations for routine childhood vaccination in states with consistently elevated rates of hepatitis A (2). Since 2002, rates in the West have been approximately equal to those in other regions of the United States (Figures 2 and 3).
Rates by Age
Incidence of hepatitis A varies by age. Since the last nationwide increase in 1995, the rates overall declined among all age groups, but the greatest decreases were among children. Historically, the highest rates were observed among children and young adults; the lowest rates were among persons aged ≥40 years. In 2007, rates were highest for persons aged 25--39 years (1.3 cases per 100,000 population) (Figure 4). During 2001--2007, the lowest rates were among children aged <5 years. However, asymptomatic infection is common among young children, and symptomatic cases in children aged <5 years represent only a limited proportion of infections that occur in this age group.
Rates by Sex
Rates of hepatitis A consistently have been higher among males than among females; during 1996--2002, the difference in the sex-specific rates increased until nearly two male cases were observed for every female case. However, since 2002, overall rates have declined more among males than among females. In 2007, incidence among males was 1.1 cases per 100,000 population, compared with 0.9 cases per 100,000 population among females (Figure 5). The difference in hepatitis A rates by sex was highest among persons aged 35--49 years (Figure 6).
Rates by Race and Ethnicity
Hepatitis A rates have differed historically by race; the highest rates occurred among American Indian/Alaska Natives (AI/ANs), and the lowest rates among Asians/Pacific Islanders (APIs). However, rates among AI/ANs, which were >60 cases per 100,000 population before 1996, have decreased dramatically; during 2001--2007, rates among AI/ANs were lower than or similar to those for other races. In 2007, the rate for AI/ANs was 0.5 cases per 100,000 population. Historically, hepatitis A rates also have differed by ethnicity; rates among Hispanics were consistently higher compared with non-Hispanics. Rates for Hispanics decreased 94%, from the peak of 24.1 cases per 100,000 population in 1997 to 1.4 cases per 100,000 population in 2007, the lowest rate ever recorded, and approached the rate for non-Hispanics (Figure 7).
Reported Risk Factors
In 2007, among cases for which information regarding exposures during the incubation period was collected, the most frequently identified risk factor for hepatitis A was international travel (reported by 18% of case patients overall). As in previous years, the majority of travel-related cases were associated with travel to Mexico and Central/South America (85%). As HAV transmission in the United States has decreased, cases among travelers to countries in which hepatitis is endemic have accounted for an increased proportion of all cases.
Historically, sexual and household contact with another person with hepatitis A has been among the most frequently identified risks; in 2007, this type of contact accounted for 8% of reported cases. In 2007, the proportion of cases reported among MSM was 6%, and the proportion of cases in persons reporting IDU was 1% (Table 4; Figure 8). Risk factor data were not available for 1,486 (50%) of reported cases (Table 4).
Clinical Characteristics
In 2007, the clinical characteristics of reported hepatitis A cases were similar to previous years; 73% of infected persons had jaundice, 35% were hospitalized for hepatitis A, and 0.8% died from hepatitis A. The proportion of persons hospitalized increased with age, from 21% among children aged <5 years to 53% among persons aged ≥60 years (Table 5).
Acute Hepatitis B
Overall Incidence
In 2007, a total of 4,519 acute, symptomatic cases of hepatitis B were reported nationwide. The overall incidence (1.5 cases per 100,000 population) was the lowest ever recorded and represents a decline of 82% from the rate in 1990 (8.5 cases per 100,000 population) (Tables 2 and 6; Figure 9). After asymptomatic infection and underreporting were taken into account, an estimated 43,000 new infections occurred in 2007 (8).
Rates by Region
In 2007, hepatitis B rates were similar to those in 2006 in all U.S. regions (Figures 10 and 11). During 2000--2007, the highest rates occurred in the South.
Rates by Age
Within each age group, hepatitis B rates began to plateau in 2006. However, hepatitis B rates varied by age, with the highest rate in 2007 (2.9 cases per 100,000 population) reported among persons aged 25--44 years and the lowest (0.02 cases per 100,000 population) reported among persons aged <15 years. The greatest percentage declines have occurred among persons aged <15 years (98%; from 1.2 cases per 100,000 population in 1990 to 0.02 cases per 100,000 population in 2007)) and those aged 15--24 years (93%; from 13.0 cases per 100,000 population in 1990 to 0.9 cases per 100,000 population in 2007). Although not as large as the declines in the younger age groups, substantial decreases occurred among older persons; the percentage declines among persons aged 25--44 years and those aged ≥45 years were 79% and 62%, respectively (Figure 12).
Rates by Sex
As in previous years, in 2007, the rate of acute hepatitis B for males (1.9 cases per 100,000 population) was higher than that for females (1.2 cases per 100,000 population). During 1990--2007, the male-to-female ratio of cases remained stable (1.5--1.8). In 2007, the rate for males was approximately 1.6 times higher than that for females (Figure 13). In 2007, this difference in hepatitis B rates by sex occurred primarily among persons aged >19 years and increased with age (Figure 14).
Rates by Race and Ethnicity
Since 2004, rates of hepatitis B have plateaued among all racial/ethnic populations (Figure 15). In 2007, the rate of hepatitis B was highest for non-Hispanic blacks (2.3 cases per 100,000 population). The downward trend in the rate among APIs continued, and the rate for this population in 2007 (0.9 cases per 100,000 population) was similar to that for Hispanics and non-Hispanic whites (1.0 case per 100,000 population, for both populations).
Reported Risk Factors for Infection
Of persons for whom information regarding exposures during the incubation period was available, 38% had multiple sex partners, 11% were MSM, and 6% had sexual contact with a person known to have hepatitis B. IDU was reported for 15% of persons. Having had surgery was reported for 12% of persons with hepatitis B; the percentage was higher for persons aged ≥45 years (17%). The proportion of persons who reported receiving hemodialysis or a blood transfusion (both of which historically were major sources of infection) or having had occupational exposure to blood was low (0.2%, 0.5%, and 0.6%, respectively) (Table 7; Figure 16). Risk factor data were not available for 2,361 (52%) of reported cases (Table 7).
Clinical Characteristics
In 2007, of persons reported with hepatitis B, 76% had jaundice, 40% were hospitalized, and 2% died. The proportion of persons hospitalized for hepatitis B was approximately 40% among persons in each age group (Table 8).
Acute Hepatitis C
Overall Incidence
In 2007, a total of 849 confirmed cases of acute hepatitis C were reported; the overall national rate was 0.3 cases per 100,000 population (Table 2 and 9; Figure 17). Since 2003, hepatitis C rates have plateaued. After asymptomatic infection and underreporting were taken into account, approximately 17,000 new HCV infections occurred in 2007 (8).
Rates by Age
Since 2003, hepatitis C rates have plateaued within each age group. In 2007, rates increased slightly among persons aged 25--39 years (0.5 per 100,000 population) and those aged ≥40 years (0.3 per 100,000 population). Rates declined 90% (from 5.3 cases per 100,000 population in 1990 to 0.5 cases per 100,000 population in 2007) among persons aged 25--39 years, the age group that historically had the highest rates of disease. Few cases were reported among persons aged <15 years (Figure 18).
Rates by Sex
In 2007, as in previous years, the reported rate of hepatitis C was higher for males (0.3 cases per 100,000 population) than for females (0.3 cases per 100,000 population). However, since 2002, this differential in rates has declined (Figure 19). In 2007, among persons aged 15--34 years, the male-to-female ratio was ≤1 (0.5 for persons aged 15--19 year, 0.8 for persons aged 20--24 years, and 1.0 for persons aged 25--29 years and for persons aged 30--34 years) (Figure 20).
Rates by Race and Ethnicity
Since 2004, the incidence of hepatitis C has plateaued among all racial/ethnic populations except for AI/ANs, for whom rates fluctuated. In 2007, rates were similar across racial/ethnic populations other than AI/ANs, for whom the rate was 0.5 cases per 100,000 population. For non-AI/AN populations, rates ranged from 0.02 cases per 100,000 population among APIs to 0.3 cases per 100,000 population among non-Hispanic whites (Figure 21).
Reported Risk Factors
Of the cases reported in 2007 for which information concerning exposures during the incubation period was available, the most common risk factor identified was IDU (48%). During 1998--2007, IDU was reported for an average of 44% of persons (range: 38%--54%). In 2007, 42% reported having multiple sex partners during the incubation period, 10% reported having sexual contact with another known HCV-infected person, and 10% were MSM. Having had surgery was reported for 20% of persons with hepatitis C; the percentage was higher for persons aged ≥40 years (32%). A total of 2% reported occupational exposure to blood (Table 10; Figure 22). Risk factor data were not available for 438 (52%) of reported cases (Table 10).
Clinical Characteristics
In 2007, of persons with hepatitis C whose cases were reported, 71% had jaundice, 49% were hospitalized, and 0.5% died (Table 11).
Discussion
National surveillance data for acute viral hepatitis provides the information needed to develop prevention strategies and monitor their effectiveness. Since national surveillance for acute viral hepatitis in the United States began in 1966, major changes in the epidemiology of these diseases have occurred. During 1995--2007, rates for all three types of acute viral hepatitis declined. These declines resulted partially from implementation of comprehensive prevention strategies for each disease, including the introduction of effective vaccines against hepatitis A and hepatitis B.
Hepatitis A
Hepatitis A rates have varied cyclically, with peaks occurring approximately every 10--15 years; the most recent peak in morbidity occurred in 1995. The incidence of hepatitis A began to decline after the introduction of licensed hepatitis A vaccines in the United States in 1995 and the issuance in 1996 of the first public health recommendations for the use of vaccine to prevent transmission of HAV (1). The greatest declines have occurred since 1999, when recommendations were made for routine vaccination of children living in states with consistently elevated rates of hepatitis A (2). After implementation of the recommended vaccination strategy, major changes occurred in the geographic distribution of hepatitis A. Relative to their prevaccine-era rates, a substantially greater decline occurred for the 17 western and midwestern states included in the 1999 recommendation than for the remainder of the country (9). As a result of this decline, hepatitis A rates now are similar across all regions.
After the implementation of routine childhood vaccination, changes in the age distribution also occurred. During the prevaccine era, the reported incidence of hepatitis A was highest among children aged 5--14 years; approximately one third of reported cases occurred among children aged <15 years. Since implementation of routine childhood vaccination, incidence has declined more sharply among the age groups (i.e., 2--18 years) covered by the recommendations than among older age groups. As a result, rates now are similar among all age groups (9). In 2007, the highest rates of disease occurred among adults, particularly among males aged 20--39 years. The low and relatively stable rates among persons aged ≥40 years reflect the higher proportion of persons in this age group who had immunity as a result of previous infection. Data from the Third National Health and Nutrition Examination Survey (NHANES III) conducted during 1988--1994 indicated that approximately 30% of the U.S. population had serologic evidence of immunity to HAV, reaching a high of 75% among persons aged ≥70 years (10).
Disparities in rates among racial/ethnic populations also decreased after the introduction of hepatitis A vaccine. In particular, rates among AI/ANs were five times those of other racial/ethnic population during the prevaccine era. Widespread use of hepatitis A vaccine in Native American communities began in 1996 (11), and rates in this population now are approximately the same or lower than those of other racial/ethnic populations. Historically, Hispanics had elevated hepatitis A rates. Incidence among Hispanics peaked in 1997 at 24.1 cases per 100,000 population and declined 94% by 2007 to 1.4 cases per 100,000 population, approaching the rate for non-Hispanics. This decline might reflect the early impact of the expansion in 2006 of the recommendation for routine vaccination to include children aged 12--23 months in all 50 states (3).
The observed declines in the incidence of hepatitis A were accompanied by shifts in the epidemiologic profile of this disease. The substantial communitywide outbreaks that occurred as a result of person-to-person contact in households and extended family settings have become increasingly rare. The disappearance of these outbreaks can be attributed to declining rates of infection among children who, because they frequently have asymptomatic infection, often have played a key role in sustaining HAV transmission. As this type of transmission has decreased, the proportion of cases among persons in high-risk populations (particularly international travelers and MSM) has increased. Although the absolute number of cases associated with international travel has remained nearly unchanged, the proportion of cases attributable to this exposure has increased, accounting for 18% of all cases in 2007. Approximately 85% of all travel-related cases were associated with travel to Mexico and to Central or South America. Hepatitis A transmission also can occur among family members of children recently adopted from countries in which hepatitis A is endemic. Family members who anticipate close personal contact with an internationally adopted child from countries in which hepatitis A is of intermediate or high endemicity can benefit from hepatitis A vaccination.
Outbreaks of hepatitis A among injection-drug users and MSM also have continued to occur although hepatitis A vaccine has been recommended for these populations since 1996.
In 2005, the licensing of hepatitis A vaccines was revised to allow vaccination of children aged 12--23 months, which has made feasible the incorporation of hepatitis A vaccine into the schedule of other routinely recommended childhood vaccines. In 2006, ACIP recommended that all children in the United States aged 12--23 months receive hepatitis A vaccine (3). Nationwide hepatitis A vaccination of children is likely to result in further narrowing of current demographic disparities and in lower overall rates of infection. The 2006 recommendations provide the foundation for eventual consideration of elimination of indigenous HAV transmission in the United States. Ongoing surveillance for acute hepatitis A provides the data needed to measure the progress toward that goal.
Hepatitis B
The decline in hepatitis B incidence began in the mid-1980s and has coincided with the stepwise implementation of the national vaccination strategy to eliminate HBV transmission. The 2007 rate of 1.5 cases per 100,000 population was the lowest recorded since surveillance began in 1966 and represents an estimated decline of >80% from the rate in 1990, the year before the national strategy was implemented.
The greatest declines have occurred among the cohort of children to whom the recommendations for routine infant and adolescent vaccination have applied. The incidence among children aged <15 years declined 98%, from 1.2 cases per 100,000 population in 1990 to 0.02 cases per 100,000 population in 2007. This decline correlates with high vaccine coverage rates among young children, with the most recent data indicating that coverage among children aged 19--35 months was 93% (12).
Although incidence also has declined among persons aged 25--44 years, rates in this age group, particularly among males, still remained substantially higher than in any other age group. A high proportion of these cases occurred among persons with risk factors for HBV infection (e.g., injection-drug users, MSM, and persons with multiple sex partners). In contrast, the continued occurrence of cases among injection-drug users and persons with sexual risk factors indicates a need to strengthen efforts to reach these populations with vaccine. In 2007, in collaboration with 54 state and local health agencies, CDC launched the Adult Hepatitis B Vaccination Initiative to provide approximately $20 million for the purchase of hepatitis B or hepatitis A/B vaccine (13). The funds supported the administration of 232,712 doses of hepatitis B containing vaccine in 1,793 clinical sites. In the second year of the initiative, 48 immunization grantees were awarded $16 million.
Since 1990, progress has been made in reducing racial/ethnic disparities in hepatitis B rates. Before 1990, APIs had disproportionately higher rates of hepatitis B. The decrease in disparity between APIs and other racial/ethnic populations was consistent with observed declines in the seroprevalence of HBV infection among high-risk Asian children after the successful implementation of routine hepatitis B vaccination (14,15). Although rates among non-Hispanic blacks have declined, they remain more than twofold higher than those among other racial/ethnic populations. Although progress has been made in reducing disparities in incidence of new infection, the impact of these disparities in the past are reflected in current prevalence patterns, with higher prevalences of chronic HBV infection among APIs and non-Hispanic blacks than among other populations.
Few cases now occur in certain populations that previously were considered to be at high risk (e.g., dialysis patients and health-care workers) as a result of continued improvements in infection control and ongoing hepatitis B vaccination in these groups. A 2003 survey indicated that approximately 75% of health-care workers have been vaccinated against hepatitis B (16). In 2002, coverage among dialysis patients was 56% (17). Persons aged ≥45 years reported surgery as a potential risk more often than those who were younger. This is probably related to the increased incidence of surgery among older persons. Approximately 40% of persons who reported having had surgery during the incubation period also reported being injection-drug users, having multiple sex partners, or being MSM. Transmission associated with transfusions is rare as a result of required screening of blood products. Health-care--related transmission of hepatitis B is documented infrequently in the United States but should be considered when cases of acute viral hepatitis are identified in persons without traditional risk factors. The declining incidence of hepatitis B has been associated with increasing recognition of sporadic cases associated with health care, including nonhospital health-care settings such as outpatient clinics and long-term care facilities (18--20). During 1999--2007, a total of 16 outbreaks of hepatitis B were detected and investigated in the United States, involving 157 known infected persons; in almost all instances, these casers could be attributed to sharing glucose-monitoring equipment among persons with diabetes residing in nursing or assisted care facilities (20). State and local health authorities should consider strategies to improve detection of hospital and nonhospital health-care--associated cases, such as targeting intensive follow-up for persons who typically are at low risk for infection (e.g., persons aged >60 years).
To complement surveillance for acute HBV infection, surveillance data also are needed to guide and evaluate public health interventions for persons with chronic hepatitis B. Approximately 800,000--1.4 million U.S. residents are living with chronic HBV infection, and hepatitis B is the underlying cause of an estimated 3,000 deaths each year in the United States. Improving the identification and public health management of persons with chronic HBV infection can help prevent serious sequelae of chronic liver disease and complement immunization strategies to eliminate HBV transmission in the United States. CDC recently issued new guidelines for HBsAg testing and including new recommendations for public health evaluation and management of chronically infected persons and their contacts (21). Surveillance data for chronic hepatitis B can be brought together with data from HIV surveillance and cancer registries to track progress to guide the integration of prevention services and health outcomes. Perinatal HBV infection, a notifiable disease, has been reported via NETSS since 2001. In 2001, a total of 30 cases were reported by seven states, and in 2004, a total of 48 cases were reported by 15 states. In 2007, a total of 83 cases were reported by 22 states. Despite the increase in the number of states reporting cases of perinatal HBV infection since 2001, not all states have begun reporting through this mechanism. The number of reported cases is estimated to represent <10% of the true number of infections occurring (22).
Hepatitis C
After peaking in the late 1980s, the incidence of hepatitis C declined steadily through the 1990s. However, since 2003, hepatitis C rates have plateaued, with IDU remaining the most commonly identified risk factor for infection. Transmission of HCV associated with transfusion, an important risk for infection in previous years, has been rare as a result of required blood screening.
Health-care--related transmission of hepatitis C is documented infrequently in the United States but should be considered when cases of acute viral hepatitis are identified in persons without traditional risk factors for hepatitis C (e.g., IDU). Recognition of sporadic cases associated with nonhospital health-care settings such as outpatient clinics and hemodialysis centers has been increasing (18--20). In 2007, an outbreak of HCV infection occurred in an endoscopy clinic in Nevada. This outbreak, which was attributed to unsafe injection practices, resulted in the notification of approximately 40,000 persons about their potential risk for exposure to HCV infection and other bloodborne pathogens; six cases of acute hepatitis C were detected (23). A review of other outbreak investigations by CDC and state health departments indicated that an additional 15 HCV outbreaks associated with receipt of care in nonhospital health-care venues had occurred in the United States during 1998--2007; 276 infected persons were identified, and >18,000 persons had been exposed and required notification and screening (20). State and local health authorities should consider strategies to improve detection of hospital and nonhospital health-care--related cases, such as targeting intensive follow-up for persons who typically are at low risk for infection (e.g., persons aged >60 years).
The incidence of acute hepatitis C has declined substantially (from 5.2 cases per 100,000 population in 1995 to 0.5 cases per 100,000 population in 2007) among persons aged 25--39 years, the age group that historically had the highest rates of infection. In 2007, cases among children continued to be rare. Progress has been made in reducing disparities in racial/ethnic-specific rates; during 2004-- 2007, the incidence of acute hepatitis C was similar across all racial/ethnic populations with the exception of AI/ANs, for whom rates were higher. Close monitoring of the incidence in specific communities remains an important tool in the detection of a disparity. However, previous racial/ethnic disparities in incidence were demonstrated by disparities in prevalence, with a higher rate of chronic infection among non-Hispanic blacks than among other racial/ethnic populations (6).
Although the number of new cases of acute hepatitis C has declined, a substantial burden of disease as a result of chronic infection still persisted in 2007. Approximately 3.2 million persons in the United States were chronically infected with HCV; the peak prevalence occurred among persons aged 40--49 years, the majority of whom likely became infected in the 1970s and 1980s, when incidence was highest (6). Data on both the incidence of acute disease and the prevalence of chronic infection are needed to assess the burden of disease attributable to HCV infection in the United States comprehensively. However, surveillance for acute hepatitis C remains critical as the best means to assess the impact of primary prevention strategies, determine where transmission continues to occur, and identify and control outbreaks.
Limitations
The analyses summarized in this report were performed on the basis of cases of symptomatic, serologically confirmed acute viral hepatitis reported to NNDSS. NNDSS is a passive surveillance system and subject to at least two limitations. First, the cases reported represent only a portion of all infections. Surveillance for acute disease is not intended to identify asymptomatic infections, and certain persons with symptomatic illness also are not identified and reported. Studies have estimated that for each hepatitis case reported to NNDSS, two to five cases that would meet the case definition are not reported (24,25). Second, completeness of case reports also can vary. However, available evidence suggests that no systematic changes have occurred in reporting patterns since 1990 (CDC, unpublished data, 2007). The national trends in this report also are reflected in CDC's Sentinel Counties Study of Acute Viral Hepatitis, in which the accuracy and completeness of reporting were assessed and known to be high (26). Rates based on NNDSS data represent a lower estimate of the incidence of acute viral hepatitis in the United States because not all cases of acute hepatitis are reported. However, because the proportion of cases not reported has not changed systematically over time, these estimates accurately reflect changing trends in these diseases in the United States.
Conclusion
Surveillance for acute viral hepatitis accomplishes multiple key public health objectives. Surveillance detects outbreaks, identifies persons in need of postexposure prophylaxis, and provides information on trends in the incidence and risks for recent infection that is needed to develop and evaluate prevention strategies. The minimum data required to conduct surveillance for acute viral hepatitis are laboratory confirmation of cases to distinguish the types of acute hepatitis and clinical information to verify the case definition. The collection of risk data provides valuable information for identifying modes of hepatitis transmission and for implementing and evaluating prevention strategies.
With continuing declines in the incidence of all types of acute viral hepatitis, surveillance efforts should be enhanced to ensure complete and accurate reporting of all cases so that the impact of strategies for preventing or eliminating transmission of these diseases can be monitored and evaluated. In addition, effective and feasible systems for conducting surveillance for chronic hepatitis virus infections are needed to characterize the burden of chronic disease that remains in the United States as a result of these infections.
Acknowledgment
Data for this report were provided by State and Territorial Health Departments.
References
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*Midwest: Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, Ohio, South Dakota, and Wisconsin; Northeast: Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont; South: Alabama, Arkansas, Delaware, District of Columbia, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, and West Virginia; and West: Alaska, Arizona, California, Colorado, Hawaii, Idaho, Montana, Nevada, New Mexico, Oregon, Utah, Washington, and Wyoming.
Surveillance for Acute Viral Hepatitis --- United States, 2007
Danni Daniels, MS
Scott Grytdal, MPH
Annemarie Wasley, ScD
Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC
Corresponding author: Danni Daniels, MS, Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC, 1600 Clifton Rd., N.E., MS G-37, Atlanta, GA 30333. Telephone: 404-718-8596; Fax: 404-718-8585. E-mail: dld4@cdc.gov.
Abstract
Problem: In the United States, acute viral hepatitis most frequently is caused by infection with any of three distinct viruses: hepatitis A virus (HAV), hepatitis B virus (HBV), or hepatitis C virus (HCV). These unrelated viruses are transmitted through different routes and have different epidemiologic profiles. Safe and effective vaccines have been available for hepatitis B since 1981 and for hepatitis A since 1995. No vaccine exists against hepatitis C. HBV and HCV can persist as chronic infections and represent a leading cause of chronic liver disease and hepatocellular carcinoma in the United States.
Reporting Period Covered: Cases in 2007, the most recent year for which data are available, are compared with those from previous years.
Description of System: Cases of acute viral hepatitis are reported voluntarily to CDC by state and territorial health departments via CDC's National Notifiable Disease Surveillance System (NNDSS). Reports are received electronically via CDC's National Electronic Telecommunications System for Surveillance (NETSS).
Results: Acute hepatitis A incidence has declined 92%, from 12.0 cases per 100,000 population in 1995 to 1.0 case per 100,000 population in 2007, the lowest rate ever recorded. Declines were greatest among children and in those states where routine vaccination of children was recommended beginning in 1999. Acute hepatitis B incidence has declined 82%, from 8.5 cases per 100,000 population in 1990 to 1.5 cases per 100,000 population in 2007, the lowest rate ever recorded. Declines occurred among all age groups but were greatest among children aged <15 years. Following a peak in 1992, incidence of acute hepatitis C declined; however, since 2003, rates have plateaued. In 2007, as in previous years, the majority of these cases occurred among adults, and injection-drug use was the most common risk factor.
Interpretation: The results documented in this report suggest that implementation of the 1999 recommendations for routine childhood hepatitis A vaccination in areas of the United States with consistently elevated hepatitis A rates has reduced rates of infection. In addition, universal vaccination of children against hepatitis B beginning in 1991 has reduced disease incidence substantially among younger age groups. Higher rates of hepatitis B continue among adults, particularly among males aged 30--44 years, reflecting the need to vaccinate adults at risk for HBV infection. The decline in hepatitis C incidence after 1992 was attributable primarily to a decrease in incidence among injection-drug users. The reasons for this decrease were unknown but probably reflected changes in behavior and practices among injection-drug users.
Public Health Actions: The expansion in 2006 of recommendations for routine hepatitis A vaccination to include all children in the United States aged 12--23 months is expected to reduce hepatitis A rates further. Ongoing hepatitis B vaccination programs ultimately will eliminate domestic HBV transmission, and increased vaccination of adults with risk factors will accelerate progress toward elimination. Further prevention of hepatitis B and hepatitis C relies on identifying and preventing transmission of HBV or HCV in hospital and nonhospital health-care associated settings. In addition, prevention of hepatitis C relies on identifying and counseling uninfected persons at risk for hepatitis C (e.g., injection-drug users) regarding ways they can protect themselves from infection. Public health management of persons with chronic HBV or HCV infection will help to interrupt the transmission to susceptible persons, and their medical management will help to reduce the development of the sequelae from chronic liver disease.
Introduction
Viral hepatitis is caused by infection with any of at least five distinct viruses, of which the three most commonly identified in the United States are hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV). All three of these unrelated viruses can produce an acute illness characterized by nausea, malaise, abdominal pain, and jaundice. HBV and HCV also can produce a chronic infection that is associated with an increased risk for chronic liver disease and hepatocellular carcinoma.
This report describes the burden of acute disease attributed to infection with HAV, HBV, and HCV and describes acute disease trends in recent years. These data can be used to develop and evaluate prevention strategies and to identify persons in need of postexposure prophylaxis. The data on acute illness presented in this report do not include the burden of disease caused by chronic infection with HBV or HCV, both of which remain a substantial public health problem.
Hepatitis A Virus
HAV is transmitted through the fecal-oral route, spreading primarily through close personal contact. During 1987--1997, an average of 28,000 cases of hepatitis A occurred per year in the United States (range: 23,112--35,821), making hepatitis A one of the country's most frequently reported notifiable diseases. However, effective vaccines to prevent hepatitis A virus infection have been available in the United States since 1995. These vaccines have provided public health authorities with the opportunity to reduce disease incidence in the United States substantially and potentially to eliminate indigenous transmission.
In 1996, CDC's Advisory Committee on Immunization Practices (ACIP) recommended administration of hepatitis A vaccine for persons at increased risk, including international travelers, men who have sex with men (MSM), injection- and noninjection-drug users, and children living in communities with high rates of disease (1). In 1999, ACIP also recommended that routine vaccination be implemented for children living in 11 states with average hepatitis A rates during 1987--1997 of ≥20 cases per 100,000 population and also be considered for children in six states with rates of 10--20 cases per 100,000 population (2). In 2006, ACIP expanded these recommendations to include routine vaccination of children in all 50 states (3).
Hepatitis B Virus
HBV is transmitted by percutaneous or mucosal exposure to the blood or body fluids of an infected person, most often through injection-drug use (IDU), sexual contact with an infected person, or contact from an infected mother to her infant during delivery. Transmission of HBV also can occur in settings involving nonsexual interpersonal contact for an extended period (e.g., among household contacts of a person with chronic HBV infection). In 1991, a comprehensive strategy was recommended for the elimination of HBV transmission in the United States (4,5). The four elements of this strategy are 1) universal vaccination of infants beginning at birth, 2) prevention of perinatal HBV infection through routine screening of all pregnant women for HBV infection and the provision of immunoprophylaxis to infants born to infected women or to women of unknown infection status, 3) routine vaccination of previously unvaccinated children and adolescents, and 4) vaccination of adults at increased risk for infection (including health-care workers, dialysis patients, household contacts and sex partners of persons with chronic HBV infection, recipients of certain blood products, persons with a recent history of multiple sex partners or a sexually transmitted disease, MSM, and injection-drug users).
Hepatitis C Virus
HCV is transmitted primarily through percutaneous exposure; however, transmission can occur through unapparent percutaneous or mucosal exposures (e.g., persons with evidence of high-risk sexual practices). With an estimated 3.2 million chronically infected persons nationwide, HCV infection is the most common bloodborne infection in the United States (6). No vaccine against HCV infection exists. National recommendations for prevention and control of HCV infection (7), issued in 1998, emphasize primary prevention activities to reduce the risk for HCV transmission. These activities include screening and testing of blood donors, viral inactivation of plasma-derived products, risk-reduction counseling and screening of persons at risk for HCV infection, and routine practice of infection control in health-care settings.
Methods
Conditions for Which Surveillance is Conducted
National surveillance is conducted for acute hepatitis A, B, and C. The case definitions for these conditions are approved by the Council of State and Territorial Epidemiologists (CSTE) and are provided (see Case Definitions for Acute Viral Hepatitis).
Data Sources
Cases of acute viral hepatitis are reported to CDC weekly by state and territorial health departments to CDC's National Notifiable Diseases Surveillance System (NNDSS). Since January 1, 2002, all reports have been submitted electronically to CDC via the National Electronic Telecommunications System for Surveillance (NETSS).
States' participation in reporting nationally notifiable diseases, including acute viral hepatitis, is voluntary. All states collect and report basic information (e.g., event date, source of report, and demographic characteristics) regarding cases of acute viral hepatitis that are identified in their states. States also are asked to report additional information (e.g., laboratory test results, clinical information, and exposure history) regarding investigated cases, but completeness of reporting of these additional data varies. Information regarding state-specific reporting profiles for risk factor information is provided in this report (Table 1).
Case Definitions for Acute Viral Hepatitis
In 2007, cases were required to meet the clinical definition for acute hepatitis and virus-specific laboratory criteria for diagnosis specified in the following CSTE-approved case definitions (available at http://www.cdc.gov/ncphi/disss/nndss/casedef/case_definitions.htm#h).
Clinical Case Definition
Acute hepatitis was defined as acute illness with 1) discrete onset of symptoms (e.g., nausea, anorexia, fever, malaise, or abdominal pain) and 2) jaundice or elevated serum aminotransferase levels. For acute hepatitis C, elevated serum aminotransferase levels are specified as serum alanine aminotransferase levels of >400 IU/L.
Laboratory Criteria for Diagnosis of Hepatitis
Because the clinical characteristics are the same for all types of acute viral hepatitis, laboratory testing is needed to identify the specific viral cause of illness. The laboratory criteria for confirming each type of acute viral hepatitis are as follows:
•Acute hepatitis A
-- Immunoglobulin M (IgM) antibody to hepatitis A virus (anti-HAV) positive
•Acute hepatitis B
-- IgM antibody to hepatitis B core antigen (anti-HBc) positive or hepatitis B surface antigen (HBsAg) positive, and
-- IgM anti-HAV negative (if performed)
•Acute hepatitis C
-- IgM anti-HAV negative, and
-- IgM anti-HBc negative, and
--One of the following:
•Antibody to hepatitis C virus (anti-HCV) screening-test-positive with a signal to cut-off ratio predictive of a true positive for the particular assay as defined by CDC (signal to cut-off rations available at http:/www.cdc.gov/hepatitis/HCV/LabTesting.htm#section1),
OR
•Hepatitis C virus recombinant immunoblot assay (HCV RIBA) positive,
OR
•Nucleic acid test (NAT) for HCV RNA positive.
Case Classification
For this analysis, a confirmed case was one if it met the clinical case definition and was laboratory-confirmed. For hepatitis A, a case also was considered confirmed that met the clinical case definition and was diagnosed in a person who had an epidemiologic link to a person who had laboratory-confirmed hepatitis A (i.e., household or sexual contact with an infected person during the 15--50 days before the onset of symptoms).
Analyses
Incidence Calculations
For this report, crude rates per 100,000 population were calculated using Bureau of the Census estimates of the U.S. resident population in 2007. The following U.S. geographic regions were used: Midwest, Northeast, South, and West.*
Frequency Analysis
For this analysis, the percentage of persons who reported a specific risk factor was determined by using the number of cases reporting any information, positive or negative, regarding that exposure as the denominator. Depending on the type of hepatitis, the percentage of case reports that included any risk factor information ranged from 48%--50%. Multiple risk factors may be reported for a single person. Consequently, the percentages of persons with specific risk factors might total >100%.
Estimation Calculation
The estimation procedure for the number of new cases of acute hepatitis A begins with the number of acute hepatitis A cases reported voluntarily to CDC via CDC's NNDSS. The overall procedure makes two adjustments to the reported number of acute hepatitis A cases: one adjustment accounts for underreporting of cases to the passive surveillance system, and the other adjustment accounts for anicteric infections assumed not to have been recognized or reported. The result of these adjustments yields the estimated number of new cases of acute hepatitis A. The procedure for estimating the number of new cases of acute hepatitis B and acute hepatitis C is similar to that for acute hepatitis A (8).
Results
Acute Hepatitis A
Overall Incidence
Historically, acute hepatitis A rates have varied cyclically, with nationwide increases every 10--15 years. The national rate of hepatitis A has declined steadily since the last peak in 1995. In 2007, a total of 2,979 acute symptomatic cases of hepatitis A were reported; the national incidence (1.0 case per 100,000 population) was the lowest ever recorded (Figure 1; Tables 2 and 3). After asymptomatic infection and underreporting were taken into account, an estimated 25,000 new infections occurred in 2007 (8).
Rates by Region
In addition to temporal variation, historically, hepatitis A rates have varied geographically, with higher rates reported in the western region of the United States. However, incidence in the West declined substantially, most notably after issuance in 1999 of recommendations for routine childhood vaccination in states with consistently elevated rates of hepatitis A (2). Since 2002, rates in the West have been approximately equal to those in other regions of the United States (Figures 2 and 3).
Rates by Age
Incidence of hepatitis A varies by age. Since the last nationwide increase in 1995, the rates overall declined among all age groups, but the greatest decreases were among children. Historically, the highest rates were observed among children and young adults; the lowest rates were among persons aged ≥40 years. In 2007, rates were highest for persons aged 25--39 years (1.3 cases per 100,000 population) (Figure 4). During 2001--2007, the lowest rates were among children aged <5 years. However, asymptomatic infection is common among young children, and symptomatic cases in children aged <5 years represent only a limited proportion of infections that occur in this age group.
Rates by Sex
Rates of hepatitis A consistently have been higher among males than among females; during 1996--2002, the difference in the sex-specific rates increased until nearly two male cases were observed for every female case. However, since 2002, overall rates have declined more among males than among females. In 2007, incidence among males was 1.1 cases per 100,000 population, compared with 0.9 cases per 100,000 population among females (Figure 5). The difference in hepatitis A rates by sex was highest among persons aged 35--49 years (Figure 6).
Rates by Race and Ethnicity
Hepatitis A rates have differed historically by race; the highest rates occurred among American Indian/Alaska Natives (AI/ANs), and the lowest rates among Asians/Pacific Islanders (APIs). However, rates among AI/ANs, which were >60 cases per 100,000 population before 1996, have decreased dramatically; during 2001--2007, rates among AI/ANs were lower than or similar to those for other races. In 2007, the rate for AI/ANs was 0.5 cases per 100,000 population. Historically, hepatitis A rates also have differed by ethnicity; rates among Hispanics were consistently higher compared with non-Hispanics. Rates for Hispanics decreased 94%, from the peak of 24.1 cases per 100,000 population in 1997 to 1.4 cases per 100,000 population in 2007, the lowest rate ever recorded, and approached the rate for non-Hispanics (Figure 7).
Reported Risk Factors
In 2007, among cases for which information regarding exposures during the incubation period was collected, the most frequently identified risk factor for hepatitis A was international travel (reported by 18% of case patients overall). As in previous years, the majority of travel-related cases were associated with travel to Mexico and Central/South America (85%). As HAV transmission in the United States has decreased, cases among travelers to countries in which hepatitis is endemic have accounted for an increased proportion of all cases.
Historically, sexual and household contact with another person with hepatitis A has been among the most frequently identified risks; in 2007, this type of contact accounted for 8% of reported cases. In 2007, the proportion of cases reported among MSM was 6%, and the proportion of cases in persons reporting IDU was 1% (Table 4; Figure 8). Risk factor data were not available for 1,486 (50%) of reported cases (Table 4).
Clinical Characteristics
In 2007, the clinical characteristics of reported hepatitis A cases were similar to previous years; 73% of infected persons had jaundice, 35% were hospitalized for hepatitis A, and 0.8% died from hepatitis A. The proportion of persons hospitalized increased with age, from 21% among children aged <5 years to 53% among persons aged ≥60 years (Table 5).
Acute Hepatitis B
Overall Incidence
In 2007, a total of 4,519 acute, symptomatic cases of hepatitis B were reported nationwide. The overall incidence (1.5 cases per 100,000 population) was the lowest ever recorded and represents a decline of 82% from the rate in 1990 (8.5 cases per 100,000 population) (Tables 2 and 6; Figure 9). After asymptomatic infection and underreporting were taken into account, an estimated 43,000 new infections occurred in 2007 (8).
Rates by Region
In 2007, hepatitis B rates were similar to those in 2006 in all U.S. regions (Figures 10 and 11). During 2000--2007, the highest rates occurred in the South.
Rates by Age
Within each age group, hepatitis B rates began to plateau in 2006. However, hepatitis B rates varied by age, with the highest rate in 2007 (2.9 cases per 100,000 population) reported among persons aged 25--44 years and the lowest (0.02 cases per 100,000 population) reported among persons aged <15 years. The greatest percentage declines have occurred among persons aged <15 years (98%; from 1.2 cases per 100,000 population in 1990 to 0.02 cases per 100,000 population in 2007)) and those aged 15--24 years (93%; from 13.0 cases per 100,000 population in 1990 to 0.9 cases per 100,000 population in 2007). Although not as large as the declines in the younger age groups, substantial decreases occurred among older persons; the percentage declines among persons aged 25--44 years and those aged ≥45 years were 79% and 62%, respectively (Figure 12).
Rates by Sex
As in previous years, in 2007, the rate of acute hepatitis B for males (1.9 cases per 100,000 population) was higher than that for females (1.2 cases per 100,000 population). During 1990--2007, the male-to-female ratio of cases remained stable (1.5--1.8). In 2007, the rate for males was approximately 1.6 times higher than that for females (Figure 13). In 2007, this difference in hepatitis B rates by sex occurred primarily among persons aged >19 years and increased with age (Figure 14).
Rates by Race and Ethnicity
Since 2004, rates of hepatitis B have plateaued among all racial/ethnic populations (Figure 15). In 2007, the rate of hepatitis B was highest for non-Hispanic blacks (2.3 cases per 100,000 population). The downward trend in the rate among APIs continued, and the rate for this population in 2007 (0.9 cases per 100,000 population) was similar to that for Hispanics and non-Hispanic whites (1.0 case per 100,000 population, for both populations).
Reported Risk Factors for Infection
Of persons for whom information regarding exposures during the incubation period was available, 38% had multiple sex partners, 11% were MSM, and 6% had sexual contact with a person known to have hepatitis B. IDU was reported for 15% of persons. Having had surgery was reported for 12% of persons with hepatitis B; the percentage was higher for persons aged ≥45 years (17%). The proportion of persons who reported receiving hemodialysis or a blood transfusion (both of which historically were major sources of infection) or having had occupational exposure to blood was low (0.2%, 0.5%, and 0.6%, respectively) (Table 7; Figure 16). Risk factor data were not available for 2,361 (52%) of reported cases (Table 7).
Clinical Characteristics
In 2007, of persons reported with hepatitis B, 76% had jaundice, 40% were hospitalized, and 2% died. The proportion of persons hospitalized for hepatitis B was approximately 40% among persons in each age group (Table 8).
Acute Hepatitis C
Overall Incidence
In 2007, a total of 849 confirmed cases of acute hepatitis C were reported; the overall national rate was 0.3 cases per 100,000 population (Table 2 and 9; Figure 17). Since 2003, hepatitis C rates have plateaued. After asymptomatic infection and underreporting were taken into account, approximately 17,000 new HCV infections occurred in 2007 (8).
Rates by Age
Since 2003, hepatitis C rates have plateaued within each age group. In 2007, rates increased slightly among persons aged 25--39 years (0.5 per 100,000 population) and those aged ≥40 years (0.3 per 100,000 population). Rates declined 90% (from 5.3 cases per 100,000 population in 1990 to 0.5 cases per 100,000 population in 2007) among persons aged 25--39 years, the age group that historically had the highest rates of disease. Few cases were reported among persons aged <15 years (Figure 18).
Rates by Sex
In 2007, as in previous years, the reported rate of hepatitis C was higher for males (0.3 cases per 100,000 population) than for females (0.3 cases per 100,000 population). However, since 2002, this differential in rates has declined (Figure 19). In 2007, among persons aged 15--34 years, the male-to-female ratio was ≤1 (0.5 for persons aged 15--19 year, 0.8 for persons aged 20--24 years, and 1.0 for persons aged 25--29 years and for persons aged 30--34 years) (Figure 20).
Rates by Race and Ethnicity
Since 2004, the incidence of hepatitis C has plateaued among all racial/ethnic populations except for AI/ANs, for whom rates fluctuated. In 2007, rates were similar across racial/ethnic populations other than AI/ANs, for whom the rate was 0.5 cases per 100,000 population. For non-AI/AN populations, rates ranged from 0.02 cases per 100,000 population among APIs to 0.3 cases per 100,000 population among non-Hispanic whites (Figure 21).
Reported Risk Factors
Of the cases reported in 2007 for which information concerning exposures during the incubation period was available, the most common risk factor identified was IDU (48%). During 1998--2007, IDU was reported for an average of 44% of persons (range: 38%--54%). In 2007, 42% reported having multiple sex partners during the incubation period, 10% reported having sexual contact with another known HCV-infected person, and 10% were MSM. Having had surgery was reported for 20% of persons with hepatitis C; the percentage was higher for persons aged ≥40 years (32%). A total of 2% reported occupational exposure to blood (Table 10; Figure 22). Risk factor data were not available for 438 (52%) of reported cases (Table 10).
Clinical Characteristics
In 2007, of persons with hepatitis C whose cases were reported, 71% had jaundice, 49% were hospitalized, and 0.5% died (Table 11).
Discussion
National surveillance data for acute viral hepatitis provides the information needed to develop prevention strategies and monitor their effectiveness. Since national surveillance for acute viral hepatitis in the United States began in 1966, major changes in the epidemiology of these diseases have occurred. During 1995--2007, rates for all three types of acute viral hepatitis declined. These declines resulted partially from implementation of comprehensive prevention strategies for each disease, including the introduction of effective vaccines against hepatitis A and hepatitis B.
Hepatitis A
Hepatitis A rates have varied cyclically, with peaks occurring approximately every 10--15 years; the most recent peak in morbidity occurred in 1995. The incidence of hepatitis A began to decline after the introduction of licensed hepatitis A vaccines in the United States in 1995 and the issuance in 1996 of the first public health recommendations for the use of vaccine to prevent transmission of HAV (1). The greatest declines have occurred since 1999, when recommendations were made for routine vaccination of children living in states with consistently elevated rates of hepatitis A (2). After implementation of the recommended vaccination strategy, major changes occurred in the geographic distribution of hepatitis A. Relative to their prevaccine-era rates, a substantially greater decline occurred for the 17 western and midwestern states included in the 1999 recommendation than for the remainder of the country (9). As a result of this decline, hepatitis A rates now are similar across all regions.
After the implementation of routine childhood vaccination, changes in the age distribution also occurred. During the prevaccine era, the reported incidence of hepatitis A was highest among children aged 5--14 years; approximately one third of reported cases occurred among children aged <15 years. Since implementation of routine childhood vaccination, incidence has declined more sharply among the age groups (i.e., 2--18 years) covered by the recommendations than among older age groups. As a result, rates now are similar among all age groups (9). In 2007, the highest rates of disease occurred among adults, particularly among males aged 20--39 years. The low and relatively stable rates among persons aged ≥40 years reflect the higher proportion of persons in this age group who had immunity as a result of previous infection. Data from the Third National Health and Nutrition Examination Survey (NHANES III) conducted during 1988--1994 indicated that approximately 30% of the U.S. population had serologic evidence of immunity to HAV, reaching a high of 75% among persons aged ≥70 years (10).
Disparities in rates among racial/ethnic populations also decreased after the introduction of hepatitis A vaccine. In particular, rates among AI/ANs were five times those of other racial/ethnic population during the prevaccine era. Widespread use of hepatitis A vaccine in Native American communities began in 1996 (11), and rates in this population now are approximately the same or lower than those of other racial/ethnic populations. Historically, Hispanics had elevated hepatitis A rates. Incidence among Hispanics peaked in 1997 at 24.1 cases per 100,000 population and declined 94% by 2007 to 1.4 cases per 100,000 population, approaching the rate for non-Hispanics. This decline might reflect the early impact of the expansion in 2006 of the recommendation for routine vaccination to include children aged 12--23 months in all 50 states (3).
The observed declines in the incidence of hepatitis A were accompanied by shifts in the epidemiologic profile of this disease. The substantial communitywide outbreaks that occurred as a result of person-to-person contact in households and extended family settings have become increasingly rare. The disappearance of these outbreaks can be attributed to declining rates of infection among children who, because they frequently have asymptomatic infection, often have played a key role in sustaining HAV transmission. As this type of transmission has decreased, the proportion of cases among persons in high-risk populations (particularly international travelers and MSM) has increased. Although the absolute number of cases associated with international travel has remained nearly unchanged, the proportion of cases attributable to this exposure has increased, accounting for 18% of all cases in 2007. Approximately 85% of all travel-related cases were associated with travel to Mexico and to Central or South America. Hepatitis A transmission also can occur among family members of children recently adopted from countries in which hepatitis A is endemic. Family members who anticipate close personal contact with an internationally adopted child from countries in which hepatitis A is of intermediate or high endemicity can benefit from hepatitis A vaccination.
Outbreaks of hepatitis A among injection-drug users and MSM also have continued to occur although hepatitis A vaccine has been recommended for these populations since 1996.
In 2005, the licensing of hepatitis A vaccines was revised to allow vaccination of children aged 12--23 months, which has made feasible the incorporation of hepatitis A vaccine into the schedule of other routinely recommended childhood vaccines. In 2006, ACIP recommended that all children in the United States aged 12--23 months receive hepatitis A vaccine (3). Nationwide hepatitis A vaccination of children is likely to result in further narrowing of current demographic disparities and in lower overall rates of infection. The 2006 recommendations provide the foundation for eventual consideration of elimination of indigenous HAV transmission in the United States. Ongoing surveillance for acute hepatitis A provides the data needed to measure the progress toward that goal.
Hepatitis B
The decline in hepatitis B incidence began in the mid-1980s and has coincided with the stepwise implementation of the national vaccination strategy to eliminate HBV transmission. The 2007 rate of 1.5 cases per 100,000 population was the lowest recorded since surveillance began in 1966 and represents an estimated decline of >80% from the rate in 1990, the year before the national strategy was implemented.
The greatest declines have occurred among the cohort of children to whom the recommendations for routine infant and adolescent vaccination have applied. The incidence among children aged <15 years declined 98%, from 1.2 cases per 100,000 population in 1990 to 0.02 cases per 100,000 population in 2007. This decline correlates with high vaccine coverage rates among young children, with the most recent data indicating that coverage among children aged 19--35 months was 93% (12).
Although incidence also has declined among persons aged 25--44 years, rates in this age group, particularly among males, still remained substantially higher than in any other age group. A high proportion of these cases occurred among persons with risk factors for HBV infection (e.g., injection-drug users, MSM, and persons with multiple sex partners). In contrast, the continued occurrence of cases among injection-drug users and persons with sexual risk factors indicates a need to strengthen efforts to reach these populations with vaccine. In 2007, in collaboration with 54 state and local health agencies, CDC launched the Adult Hepatitis B Vaccination Initiative to provide approximately $20 million for the purchase of hepatitis B or hepatitis A/B vaccine (13). The funds supported the administration of 232,712 doses of hepatitis B containing vaccine in 1,793 clinical sites. In the second year of the initiative, 48 immunization grantees were awarded $16 million.
Since 1990, progress has been made in reducing racial/ethnic disparities in hepatitis B rates. Before 1990, APIs had disproportionately higher rates of hepatitis B. The decrease in disparity between APIs and other racial/ethnic populations was consistent with observed declines in the seroprevalence of HBV infection among high-risk Asian children after the successful implementation of routine hepatitis B vaccination (14,15). Although rates among non-Hispanic blacks have declined, they remain more than twofold higher than those among other racial/ethnic populations. Although progress has been made in reducing disparities in incidence of new infection, the impact of these disparities in the past are reflected in current prevalence patterns, with higher prevalences of chronic HBV infection among APIs and non-Hispanic blacks than among other populations.
Few cases now occur in certain populations that previously were considered to be at high risk (e.g., dialysis patients and health-care workers) as a result of continued improvements in infection control and ongoing hepatitis B vaccination in these groups. A 2003 survey indicated that approximately 75% of health-care workers have been vaccinated against hepatitis B (16). In 2002, coverage among dialysis patients was 56% (17). Persons aged ≥45 years reported surgery as a potential risk more often than those who were younger. This is probably related to the increased incidence of surgery among older persons. Approximately 40% of persons who reported having had surgery during the incubation period also reported being injection-drug users, having multiple sex partners, or being MSM. Transmission associated with transfusions is rare as a result of required screening of blood products. Health-care--related transmission of hepatitis B is documented infrequently in the United States but should be considered when cases of acute viral hepatitis are identified in persons without traditional risk factors. The declining incidence of hepatitis B has been associated with increasing recognition of sporadic cases associated with health care, including nonhospital health-care settings such as outpatient clinics and long-term care facilities (18--20). During 1999--2007, a total of 16 outbreaks of hepatitis B were detected and investigated in the United States, involving 157 known infected persons; in almost all instances, these casers could be attributed to sharing glucose-monitoring equipment among persons with diabetes residing in nursing or assisted care facilities (20). State and local health authorities should consider strategies to improve detection of hospital and nonhospital health-care--associated cases, such as targeting intensive follow-up for persons who typically are at low risk for infection (e.g., persons aged >60 years).
To complement surveillance for acute HBV infection, surveillance data also are needed to guide and evaluate public health interventions for persons with chronic hepatitis B. Approximately 800,000--1.4 million U.S. residents are living with chronic HBV infection, and hepatitis B is the underlying cause of an estimated 3,000 deaths each year in the United States. Improving the identification and public health management of persons with chronic HBV infection can help prevent serious sequelae of chronic liver disease and complement immunization strategies to eliminate HBV transmission in the United States. CDC recently issued new guidelines for HBsAg testing and including new recommendations for public health evaluation and management of chronically infected persons and their contacts (21). Surveillance data for chronic hepatitis B can be brought together with data from HIV surveillance and cancer registries to track progress to guide the integration of prevention services and health outcomes. Perinatal HBV infection, a notifiable disease, has been reported via NETSS since 2001. In 2001, a total of 30 cases were reported by seven states, and in 2004, a total of 48 cases were reported by 15 states. In 2007, a total of 83 cases were reported by 22 states. Despite the increase in the number of states reporting cases of perinatal HBV infection since 2001, not all states have begun reporting through this mechanism. The number of reported cases is estimated to represent <10% of the true number of infections occurring (22).
Hepatitis C
After peaking in the late 1980s, the incidence of hepatitis C declined steadily through the 1990s. However, since 2003, hepatitis C rates have plateaued, with IDU remaining the most commonly identified risk factor for infection. Transmission of HCV associated with transfusion, an important risk for infection in previous years, has been rare as a result of required blood screening.
Health-care--related transmission of hepatitis C is documented infrequently in the United States but should be considered when cases of acute viral hepatitis are identified in persons without traditional risk factors for hepatitis C (e.g., IDU). Recognition of sporadic cases associated with nonhospital health-care settings such as outpatient clinics and hemodialysis centers has been increasing (18--20). In 2007, an outbreak of HCV infection occurred in an endoscopy clinic in Nevada. This outbreak, which was attributed to unsafe injection practices, resulted in the notification of approximately 40,000 persons about their potential risk for exposure to HCV infection and other bloodborne pathogens; six cases of acute hepatitis C were detected (23). A review of other outbreak investigations by CDC and state health departments indicated that an additional 15 HCV outbreaks associated with receipt of care in nonhospital health-care venues had occurred in the United States during 1998--2007; 276 infected persons were identified, and >18,000 persons had been exposed and required notification and screening (20). State and local health authorities should consider strategies to improve detection of hospital and nonhospital health-care--related cases, such as targeting intensive follow-up for persons who typically are at low risk for infection (e.g., persons aged >60 years).
The incidence of acute hepatitis C has declined substantially (from 5.2 cases per 100,000 population in 1995 to 0.5 cases per 100,000 population in 2007) among persons aged 25--39 years, the age group that historically had the highest rates of infection. In 2007, cases among children continued to be rare. Progress has been made in reducing disparities in racial/ethnic-specific rates; during 2004-- 2007, the incidence of acute hepatitis C was similar across all racial/ethnic populations with the exception of AI/ANs, for whom rates were higher. Close monitoring of the incidence in specific communities remains an important tool in the detection of a disparity. However, previous racial/ethnic disparities in incidence were demonstrated by disparities in prevalence, with a higher rate of chronic infection among non-Hispanic blacks than among other racial/ethnic populations (6).
Although the number of new cases of acute hepatitis C has declined, a substantial burden of disease as a result of chronic infection still persisted in 2007. Approximately 3.2 million persons in the United States were chronically infected with HCV; the peak prevalence occurred among persons aged 40--49 years, the majority of whom likely became infected in the 1970s and 1980s, when incidence was highest (6). Data on both the incidence of acute disease and the prevalence of chronic infection are needed to assess the burden of disease attributable to HCV infection in the United States comprehensively. However, surveillance for acute hepatitis C remains critical as the best means to assess the impact of primary prevention strategies, determine where transmission continues to occur, and identify and control outbreaks.
Limitations
The analyses summarized in this report were performed on the basis of cases of symptomatic, serologically confirmed acute viral hepatitis reported to NNDSS. NNDSS is a passive surveillance system and subject to at least two limitations. First, the cases reported represent only a portion of all infections. Surveillance for acute disease is not intended to identify asymptomatic infections, and certain persons with symptomatic illness also are not identified and reported. Studies have estimated that for each hepatitis case reported to NNDSS, two to five cases that would meet the case definition are not reported (24,25). Second, completeness of case reports also can vary. However, available evidence suggests that no systematic changes have occurred in reporting patterns since 1990 (CDC, unpublished data, 2007). The national trends in this report also are reflected in CDC's Sentinel Counties Study of Acute Viral Hepatitis, in which the accuracy and completeness of reporting were assessed and known to be high (26). Rates based on NNDSS data represent a lower estimate of the incidence of acute viral hepatitis in the United States because not all cases of acute hepatitis are reported. However, because the proportion of cases not reported has not changed systematically over time, these estimates accurately reflect changing trends in these diseases in the United States.
Conclusion
Surveillance for acute viral hepatitis accomplishes multiple key public health objectives. Surveillance detects outbreaks, identifies persons in need of postexposure prophylaxis, and provides information on trends in the incidence and risks for recent infection that is needed to develop and evaluate prevention strategies. The minimum data required to conduct surveillance for acute viral hepatitis are laboratory confirmation of cases to distinguish the types of acute hepatitis and clinical information to verify the case definition. The collection of risk data provides valuable information for identifying modes of hepatitis transmission and for implementing and evaluating prevention strategies.
With continuing declines in the incidence of all types of acute viral hepatitis, surveillance efforts should be enhanced to ensure complete and accurate reporting of all cases so that the impact of strategies for preventing or eliminating transmission of these diseases can be monitored and evaluated. In addition, effective and feasible systems for conducting surveillance for chronic hepatitis virus infections are needed to characterize the burden of chronic disease that remains in the United States as a result of these infections.
Acknowledgment
Data for this report were provided by State and Territorial Health Departments.
References
1.CDC. Prevention of hepatitis A through active or passive immunization. MMWR 1996;45(No. RR-15).
2.CDC. Prevention of hepatitis A through active or passive immunization. MMWR 1999;48(No. RR-12).
3.CDC. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2006;55(No. RR-7).
4.CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Part 1: immunization of infants, children, and adolescents. MMWR 2005;54(No. RR-16).
5.CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States---recommendations of the Advisory Committee on Immunization Practices (ACIP). Part 2: immunization of adults. MMWR 2006;55(No. RR-16).
6.Armstrong GL, Wasley AM, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med 2006;144:705--14.
7.CDC. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47(No. RR-19).
8.CDC. Estimates of disease burden from viral hepatitis. Atlanta, GA: US Department of Health and Human Services, CDC; 2007. Available at http://www.cdc.gov/hepatitis/PDFs/disease_burden.pdf.
9.Wasley A, Samandari T, Bell BP. Incidence of hepatitis A in the United States in the era of vaccination. JAMA 2005;294:194--201.
10.Bell BP, Kruszon-Moran D, Shapiro CN, et al. Hepatitis A virus infection in the United States: serologic results from the Third National Health and Nutrition Examination Survey. Vaccine 2005;23:5798--806.
11.Bialek SR, Thoroughman DA, Hu D, et al. Hepatitis A incidence and hepatitis A vaccination among American Indians and Alaska Natives, 1990--2001. Am J Public Health 2004;94:996--1001.
12.CDC. National, state, and local area vaccination coverage among children aged 19--35 months---United States, 2007. MMWR 2008;57:961--66.
13.CDC. The National Center for Immunization and Respiratory Diseases 2008 annual report. Atlanta, GA: US Department of Health and Human Services, CDC; 2008. Available at http://www.cdc.gov/ncird/annual-rpts/default.html.
14.Perz JF, Elm JL, Fiore AE, Huggler JI, Kuhnert WL, Effler PV. Near elimination of hepatitis B virus infections among Hawaii elementary school children following universal infant hepatitis B vaccination. Pediatrics 2006;118:1403--8.
15.Fiore A, Neeman R, Lee S, et al. Seroprevalence of hepatitis B virus (HBV) infection among Asian immigrants and their US-born children in Georgia [Abstract No. 586]. In: Abstracts of the Infectious Diseases Society of America 41st Annual Meeting, San Diego, California, October 9--12, 2003. Alexandria, VA: Infectious Diseases Society of America; 2003.
16.Simard E, Miller JT, George PA, et al. Hepatitis B vaccination coverage levels among health care workers in the United States, 2002--2003. Infect Control Hosp Epidemiol 2007;28:783--90.
17.Finelli L, Miller JT, Tokars JI, Alter MJ, Arduino MJ. National surveillance of dialysis-associated diseases in the United States, 2002. Sem Dialysis 2005;18:52-- 61.
18.Williams IT, Perz JF, Bell BP. Viral hepatitis transmission in ambulatory health care settings. Clin Infect Dis 2004;38:1592--8.
19.CDC. Transmission of hepatitis B and C viruses in outpatient settings---New York, Oklahoma, and Nebraska, 2000--2002. MMWR 2003;52:901--6.
20.Thompson ND, Perz JF, Moorman AC, Holmberg SD. Nonhospital health care--associated hepatitis B and C virus transmission: United States, 1998--2008. Ann Intern Med 2009;150:33--9.
21.CDC. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR 2008;57(No. RR-8).
22.Ward, JW. Time for renewed commitment to viral hepatitis prevention. Am J Pub Health 2008;98:779--81.
23.CDC. Acute hepatitis C virus infections attributed to unsafe injection practices at an endoscopy clinic---Nevada, 2007. MMWR 2008;57:513--7.
24.Doyle TJ, Glynn MK, Groseclose SL. Completeness of notifiable infectious disease reporting in the United States: an analytical literature review. Am J Epidemiol 2002;155:866--74.
25.Armstrong GL, Bell BP. Hepatitis A virus infections in the United States: model-based estimates and implications for childhood immunization. Pediatrics 2002;109:839--45.
26.Alter MJ, Mares A, Hadler SC, Maynard JE. The effect of underreporting on the apparent incidence and epidemiology of acute viral hepatitis. Am J Epidemiol 1987;125:133--9.
*Midwest: Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, Ohio, South Dakota, and Wisconsin; Northeast: Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont; South: Alabama, Arkansas, Delaware, District of Columbia, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, and West Virginia; and West: Alaska, Arizona, California, Colorado, Hawaii, Idaho, Montana, Nevada, New Mexico, Oregon, Utah, Washington, and Wyoming.
Drug Shows Promise Against Hepatitis C
Studies: Drug Shows Promise Against Hepatitis C
Abstract
The results of two recent studies of an experimental drug raise new hopes in the fight against hepatitis C virus (HCV) infection. The findings suggest the drug, telaprevir, can cut treatment time from a year to six months and raise the proportion of patients considered cured. Currently the standard treatment for hepatitis C is combination therapy with peginterferon and ribavirin. In the two studies, about two-thirds of patients who received telaprevir for six months showed no signs of HCV six months later, which doctors consider being cured. Only 40 to 50 percent of patients are cured by standard treatment alone. One study involved 250 US patients with chronic HCV. Sixty-one percent who took standard therapy with telaprevir for six months cleared the virus, compared to 41 who took standard therapy only. Sixty-seven percent who took the new drug and standard therapy for one year showed no signs of infection. Of note, however: Twice as many patients in the telaprevir group stopped treatment due to side effects. The second study involved 334 patients in Europe. After six months, 69 percent of patients on standard therapy and telaprevir had undetectable levels of HCV compared to 46 percent of patients who received standard therapy only. Shorter treatment times did not show benefit in either study. Vertex Pharmaceuticals Inc. makes telaprevir and sponsored both studies. “Telaprevir appears to be a material advance in the therapy of hepatitis C, beginning a new era of treatment,” Dr. Jay H. Hoofnagle of the National Institute of Diabetes and Digestive and Kidney Diseases wrote in an editorial accompanying the studies. “The new drug does show promise,” acknowledged hepatitis expert Dr. James Ou of the University of Southern California’s Keck School of Medicine, though he added, “its side effects remain a concern.” Telaprevir is in late-stage testing; Vertex plans to seek government approval of it next year. The studies, “Telaprevir with Peginterferon and Ribavirin for Chronic HCV Genotype 1 Infection” and “Telaprevir and Peginterferon with or Without Ribavirin for Chronic HCV Infection,” and the editorial, “A Step Forward in Therapy for Hepatitis C,” were published in the New England Journal of Medicine (2009;360(18):1827-1838, 1839-1850, and 1899-1901).
Source
http://www.ap.org/
Date of Publication
04/29/2009
Author
Alicia Chang
Subjects
Hepatitis C
Studies or Surveys
Therapeutic Drugs
Treatment
Disclaimer: NPIN provides this information as a public service only. The views and information provided about the materials, news, funding opportunities, organizations, and conferences do not necessarily state or reflect those of the U.S. Department of Health and Human Services, CDC, or NPIN.
Abstract
The results of two recent studies of an experimental drug raise new hopes in the fight against hepatitis C virus (HCV) infection. The findings suggest the drug, telaprevir, can cut treatment time from a year to six months and raise the proportion of patients considered cured. Currently the standard treatment for hepatitis C is combination therapy with peginterferon and ribavirin. In the two studies, about two-thirds of patients who received telaprevir for six months showed no signs of HCV six months later, which doctors consider being cured. Only 40 to 50 percent of patients are cured by standard treatment alone. One study involved 250 US patients with chronic HCV. Sixty-one percent who took standard therapy with telaprevir for six months cleared the virus, compared to 41 who took standard therapy only. Sixty-seven percent who took the new drug and standard therapy for one year showed no signs of infection. Of note, however: Twice as many patients in the telaprevir group stopped treatment due to side effects. The second study involved 334 patients in Europe. After six months, 69 percent of patients on standard therapy and telaprevir had undetectable levels of HCV compared to 46 percent of patients who received standard therapy only. Shorter treatment times did not show benefit in either study. Vertex Pharmaceuticals Inc. makes telaprevir and sponsored both studies. “Telaprevir appears to be a material advance in the therapy of hepatitis C, beginning a new era of treatment,” Dr. Jay H. Hoofnagle of the National Institute of Diabetes and Digestive and Kidney Diseases wrote in an editorial accompanying the studies. “The new drug does show promise,” acknowledged hepatitis expert Dr. James Ou of the University of Southern California’s Keck School of Medicine, though he added, “its side effects remain a concern.” Telaprevir is in late-stage testing; Vertex plans to seek government approval of it next year. The studies, “Telaprevir with Peginterferon and Ribavirin for Chronic HCV Genotype 1 Infection” and “Telaprevir and Peginterferon with or Without Ribavirin for Chronic HCV Infection,” and the editorial, “A Step Forward in Therapy for Hepatitis C,” were published in the New England Journal of Medicine (2009;360(18):1827-1838, 1839-1850, and 1899-1901).
Source
http://www.ap.org/
Date of Publication
04/29/2009
Author
Alicia Chang
Subjects
Hepatitis C
Studies or Surveys
Therapeutic Drugs
Treatment
Disclaimer: NPIN provides this information as a public service only. The views and information provided about the materials, news, funding opportunities, organizations, and conferences do not necessarily state or reflect those of the U.S. Department of Health and Human Services, CDC, or NPIN.
Successful HCV Treatment May Not Eliminate Risk of Transmission
Successful HCV Treatment May Not Eliminate Risk of Transmission
By Michael Smith, North American Correspondent, MedPage Today
Published: May 05, 2009
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston. Earn CME/CE credit
for reading medical news
TORONTO, May 5 -- Even after successful treatment for hepatitis C, patients may have low levels of virus that could be infectious, Canadian researchers said.
Action Points
■Note that this study -- using highly sensitive research tests -- found that viral RNA remains in some successfully treated patients and can be infectious in vitro.
Highly sensitive research tests can detect traces of the virus in patients months and even years after the conventional tests used to assess recovery come up negative, according to Tomasz Michalak, M.D., Ph.D., of Memorial University in St. John's, Newfoundland, and colleagues.
Plasma or supernatants from cultured peripheral blood mononuclear cells from such patients can then infect lymphoid cells in vitro, Dr. Michalak and colleagues reported in the May issue of Hepatology.
The findings "can be interpreted as a strong indication of potential virus infectivity in vivo," the researchers argued.
The conventional definition of successful treatment for chronic hepatitis C -- the so-called "sustained virological response" -- is lack of evidence of viral RNA in the serum for at least six months after therapy is complete.
But the tests used for that measurement have a lower limit of detection of between about 52 and 1,000 "virus genome equivalents" per milliliter of serum, Dr. Michalak and colleagues said.
In contrast, the tests they used for this study can detect fewer than 10 such virus genome equivalents per milliliter.
The researchers looked at nine patients who had a sustained virological response for between 24 and 72 months based on a commercial test able to detect 1,000 virus genome equivalents.
But, the patients had occult virus detectable by the more sensitive test at levels between 40 and 400 virus genome equivalents, the researchers reported, although one patient had a markedly higher level.
Dr. Michalak and colleagues cultured lymphoid cells from healthy donors and exposed them to plasma or to supernatants from the patients.
The exposed cells were analyzed for positive and negative strands of viral RNA, where the positive strand simply indicates the presence of the virus and the negative strand is an indication of reactive replications.
Analysis showed that 11 of the 12 cell cultures showed evidence of the positive strand hepatitis C RNA, the researchers said.
The cultures also showed the negative strand hepatitis C RNA -- evidence of active viral replication -- in three cases, they found.
"These findings provide in vitro evidence that trace quantities of (hepatitis C virus) persisting in the circulation for a long time after therapeutically induced resolution of CHC (chronic hepatitis C) can remain infectious," the authors said.
Interestingly, replication could be prevented by treating plasma from a patient with a monoclonal antibody to hepatitis C, or by treating the recipient cells with interferon-alpha, Dr. Michalak and colleagues said.
By Michael Smith, North American Correspondent, MedPage Today
Published: May 05, 2009
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston. Earn CME/CE credit
for reading medical news
TORONTO, May 5 -- Even after successful treatment for hepatitis C, patients may have low levels of virus that could be infectious, Canadian researchers said.
Action Points
■Note that this study -- using highly sensitive research tests -- found that viral RNA remains in some successfully treated patients and can be infectious in vitro.
Highly sensitive research tests can detect traces of the virus in patients months and even years after the conventional tests used to assess recovery come up negative, according to Tomasz Michalak, M.D., Ph.D., of Memorial University in St. John's, Newfoundland, and colleagues.
Plasma or supernatants from cultured peripheral blood mononuclear cells from such patients can then infect lymphoid cells in vitro, Dr. Michalak and colleagues reported in the May issue of Hepatology.
The findings "can be interpreted as a strong indication of potential virus infectivity in vivo," the researchers argued.
The conventional definition of successful treatment for chronic hepatitis C -- the so-called "sustained virological response" -- is lack of evidence of viral RNA in the serum for at least six months after therapy is complete.
But the tests used for that measurement have a lower limit of detection of between about 52 and 1,000 "virus genome equivalents" per milliliter of serum, Dr. Michalak and colleagues said.
In contrast, the tests they used for this study can detect fewer than 10 such virus genome equivalents per milliliter.
The researchers looked at nine patients who had a sustained virological response for between 24 and 72 months based on a commercial test able to detect 1,000 virus genome equivalents.
But, the patients had occult virus detectable by the more sensitive test at levels between 40 and 400 virus genome equivalents, the researchers reported, although one patient had a markedly higher level.
Dr. Michalak and colleagues cultured lymphoid cells from healthy donors and exposed them to plasma or to supernatants from the patients.
The exposed cells were analyzed for positive and negative strands of viral RNA, where the positive strand simply indicates the presence of the virus and the negative strand is an indication of reactive replications.
Analysis showed that 11 of the 12 cell cultures showed evidence of the positive strand hepatitis C RNA, the researchers said.
The cultures also showed the negative strand hepatitis C RNA -- evidence of active viral replication -- in three cases, they found.
"These findings provide in vitro evidence that trace quantities of (hepatitis C virus) persisting in the circulation for a long time after therapeutically induced resolution of CHC (chronic hepatitis C) can remain infectious," the authors said.
Interestingly, replication could be prevented by treating plasma from a patient with a monoclonal antibody to hepatitis C, or by treating the recipient cells with interferon-alpha, Dr. Michalak and colleagues said.
Successful HCV Treatment May Not Eliminate Risk of Transmission
Successful HCV Treatment May Not Eliminate Risk of Transmission
By Michael Smith, North American Correspondent, MedPage Today
Published: May 05, 2009
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston. Earn CME/CE credit
for reading medical news
TORONTO, May 5 -- Even after successful treatment for hepatitis C, patients may have low levels of virus that could be infectious, Canadian researchers said.
Action Points
■Note that this study -- using highly sensitive research tests -- found that viral RNA remains in some successfully treated patients and can be infectious in vitro.
Highly sensitive research tests can detect traces of the virus in patients months and even years after the conventional tests used to assess recovery come up negative, according to Tomasz Michalak, M.D., Ph.D., of Memorial University in St. John's, Newfoundland, and colleagues.
Plasma or supernatants from cultured peripheral blood mononuclear cells from such patients can then infect lymphoid cells in vitro, Dr. Michalak and colleagues reported in the May issue of Hepatology.
The findings "can be interpreted as a strong indication of potential virus infectivity in vivo," the researchers argued.
The conventional definition of successful treatment for chronic hepatitis C -- the so-called "sustained virological response" -- is lack of evidence of viral RNA in the serum for at least six months after therapy is complete.
But the tests used for that measurement have a lower limit of detection of between about 52 and 1,000 "virus genome equivalents" per milliliter of serum, Dr. Michalak and colleagues said.
In contrast, the tests they used for this study can detect fewer than 10 such virus genome equivalents per milliliter.
The researchers looked at nine patients who had a sustained virological response for between 24 and 72 months based on a commercial test able to detect 1,000 virus genome equivalents.
But, the patients had occult virus detectable by the more sensitive test at levels between 40 and 400 virus genome equivalents, the researchers reported, although one patient had a markedly higher level.
Dr. Michalak and colleagues cultured lymphoid cells from healthy donors and exposed them to plasma or to supernatants from the patients.
The exposed cells were analyzed for positive and negative strands of viral RNA, where the positive strand simply indicates the presence of the virus and the negative strand is an indication of reactive replications.
Analysis showed that 11 of the 12 cell cultures showed evidence of the positive strand hepatitis C RNA, the researchers said.
The cultures also showed the negative strand hepatitis C RNA -- evidence of active viral replication -- in three cases, they found.
"These findings provide in vitro evidence that trace quantities of (hepatitis C virus) persisting in the circulation for a long time after therapeutically induced resolution of CHC (chronic hepatitis C) can remain infectious," the authors said.
Interestingly, replication could be prevented by treating plasma from a patient with a monoclonal antibody to hepatitis C, or by treating the recipient cells with interferon-alpha, Dr. Michalak and colleagues said.
By Michael Smith, North American Correspondent, MedPage Today
Published: May 05, 2009
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston. Earn CME/CE credit
for reading medical news
TORONTO, May 5 -- Even after successful treatment for hepatitis C, patients may have low levels of virus that could be infectious, Canadian researchers said.
Action Points
■Note that this study -- using highly sensitive research tests -- found that viral RNA remains in some successfully treated patients and can be infectious in vitro.
Highly sensitive research tests can detect traces of the virus in patients months and even years after the conventional tests used to assess recovery come up negative, according to Tomasz Michalak, M.D., Ph.D., of Memorial University in St. John's, Newfoundland, and colleagues.
Plasma or supernatants from cultured peripheral blood mononuclear cells from such patients can then infect lymphoid cells in vitro, Dr. Michalak and colleagues reported in the May issue of Hepatology.
The findings "can be interpreted as a strong indication of potential virus infectivity in vivo," the researchers argued.
The conventional definition of successful treatment for chronic hepatitis C -- the so-called "sustained virological response" -- is lack of evidence of viral RNA in the serum for at least six months after therapy is complete.
But the tests used for that measurement have a lower limit of detection of between about 52 and 1,000 "virus genome equivalents" per milliliter of serum, Dr. Michalak and colleagues said.
In contrast, the tests they used for this study can detect fewer than 10 such virus genome equivalents per milliliter.
The researchers looked at nine patients who had a sustained virological response for between 24 and 72 months based on a commercial test able to detect 1,000 virus genome equivalents.
But, the patients had occult virus detectable by the more sensitive test at levels between 40 and 400 virus genome equivalents, the researchers reported, although one patient had a markedly higher level.
Dr. Michalak and colleagues cultured lymphoid cells from healthy donors and exposed them to plasma or to supernatants from the patients.
The exposed cells were analyzed for positive and negative strands of viral RNA, where the positive strand simply indicates the presence of the virus and the negative strand is an indication of reactive replications.
Analysis showed that 11 of the 12 cell cultures showed evidence of the positive strand hepatitis C RNA, the researchers said.
The cultures also showed the negative strand hepatitis C RNA -- evidence of active viral replication -- in three cases, they found.
"These findings provide in vitro evidence that trace quantities of (hepatitis C virus) persisting in the circulation for a long time after therapeutically induced resolution of CHC (chronic hepatitis C) can remain infectious," the authors said.
Interestingly, replication could be prevented by treating plasma from a patient with a monoclonal antibody to hepatitis C, or by treating the recipient cells with interferon-alpha, Dr. Michalak and colleagues said.
Tuesday, June 2, 2009
Liver Cancer HCC tripled in the United States from 1975 through 2005
Journal of Clinical Oncology, Vol 27, No 9 (March 20), 2009: pp. 1485-1491
"The principal findings in this report were that incidence rates of HCC tripled in the United States from 1975 through 2005, with marked recent increases among middle-aged black, Hispanic, and white males"
"Overall age-adjusted incidence rates of HCC tripled between 1975 and 2005, rising from 1.6 per 100,000 to 4.9 per 100,000.....Between 1992 and 2005, overall incidence rates of HCC increased, with an annual percent change of 4.3% (P ≤ .05).....American Indians/Alaska Natives experienced the greatest significant increase (APC = 5.0%), followed by blacks (APC = 4.9%), whites (APC = 4.6%), and Hispanics (APC = 4.0%), look at Table 1 below and you'll much higher incidence rates among Blacks & Hispanics compared to whites, the affects are disproportionate in terms of having HCC and deaths due to HCC (from Jules: this is likely to worse access to care, poor treatment decision making, and undiagnosed HCV/HBV and HCC........(from Jules: there is little or no HCV screening and screening for HCC. There is no Federal support for national screening and surveillance of HCV)......Coordination of existing HCC prevention efforts is needed. Gaps in HCC screening in the United States include limited HCV testing of current and former injected drug users,33 pre-1990 transfusion recipients,34 and incomplete HBV testing of foreign-born Asians/Pacific Islanders.35 In addition, cultural and economic barriers to HCC screening of chronic viral carriers existMuch of the increase in incidence between 2000 and 2005 occurred among men age 50 to 59 years. Not all racial/ethnic groups were equally affected, with black, Hispanic, and white men experiencing the greatest increases.....The changing racial pattern of HCC in this age group may be partially attributable to an epidemic of HCV infection that occurred approximately four decades earlier, in the 1960s, when they were young adults.10 Several findings in this report suggest, however, that risk of HCC is likely to be driven by additional factors.....HCC incidence rates are reported to be higher among Hispanics born in the United States than among foreign-born Hispanics.23 This suggests that factors associated with life in the United States, perhaps including HCV infection,10 alcohol abuse,24 or obesity,25 may be adversely affecting Hispanic populations. here is a need for studies to estimate the current proportion of HCCs that are attributed to HCV and to HBV including differences across demographic groups.9,39..... Associations with suspected cofactors for HCC should also be examined, including alcoholism24 and steatohepatitis,25 obesity,42 diabetes mellitus,43 and iron storage diseases.44.....This report may underestimate recent increases in HCC incidence rates because of delays in reporting16 and an estimated rate of under-reporting of 2.5% because of absence of data on Veterans' Affairs hospital patients,5 a population which may be at elevated risk for HCC compared with the general population"
Hepatocellular Carcinoma Incidence, Mortality, and Survival Trends in the United States From 1975 to 2005
Sean F. Altekruse, Katherine A. McGlynn, Marsha E. Reichman
From the Division of Cancer Control and Population Sciences, and the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Corresponding author: Sean F. Altekruse, DVM, MPH, PhD, Cancer Statistics Branch, Division of Cancer Control and Population Sciences, National Cancer Institute, 6116 Executive Blvd Suite 504, Bethesda, MD 20892-8316; e-mail: altekrusesf@mail.nih.gov.
ABSTRACT
Purpose - Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Incidence rates are increasing in the United States. Monitoring incidence, survival, and mortality rates within at-risk populations can facilitate control efforts.
Methods - Age-adjusted incidence trends for HCC were examined in the Surveillance, Epidemiology, and End Results (SEER) registries from 1975 to 2005. Age-specific rates were examined for birth cohorts born between 1900 and 1959. Age-adjusted incidence and cause-specific survival rates from 1992 to 2005 were examined in the SEER 13 registries by race/ethnicity, stage, and treatment. United States liver cancer mortality rates were also examined.
Results - Age-adjusted HCC incidence rates tripled between 1975 and 2005. Incidence rates increased in each 10-year birth cohort from 1900 through the 1950s. Asians/Pacific Islanders had higher incidence and mortality rates than other racial/ethnic groups, but experienced a significant decrease in mortality rates over time. From 2000 to 2005, marked increases in incidence rates occurred among Hispanic, black, and white middle-aged men. Between 1992 and 2004, 2- to 4-year HCC survival rates doubled, as more patients were diagnosed with localized and regional HCC and prognosis improved, particularly for patients with reported treatment. Recent 1-year survival rates remained, however, less than 50%.
Conclusion - HCC incidence and mortality rates continue to increase, particularly among middle-aged black, Hispanic, and white men. Screening of at-risk groups and treatment of localized-stage tumors may contribute to increasing HCC survival rates in the United States. More progress is needed.
INTRODUCTION
Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide.1 This malignancy occurs more often among men than women, with the highest incidence rates reported in East Asia.2 The incidence rates of HCC in the United States have historically been lower than in many countries. However, in recent decades, HCC age-adjusted incidence rates have doubled3 and primary liver cancer mortality rates have increased faster than mortality rates for any other leading cause of cancer.4,5 Approximately 90% of primary liver cancers in the United States are HCCs, while most of the remaining 10% are intrahepatic cholangiocarcinomas.6 The pathway leading to HCC generally begins with an acute hepatic insult which progresses over decades. Fibrosis and cirrhosis are typically precursors of HCC.7 Among patients with localized stage HCC, treatment options may include resection or transplantation. Chemoembolization, a combination of chemotherapy and occlusion of the tumor blood supply, is reported to improve survival in well-selected patients with unresectable HCC.8 Many patients who are diagnosed with HCC, however, have advanced disease and are only candidates for palliative care, contributing to a relatively low reported 5-year survival rate of approximately 10%.6
Most HCC is thought to be associated with either chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection.9 In the United States, more than 3 million people are chronically infected with HCV.10 Many of these individuals were exposed as young adults beginning in the 1960s.10,11 HCV risk factors include contaminated blood product transfusion and injected drug use.10,11
Chronic infection with HBV, a major global risk factor for HCC, is less common overall in the United States than HCV infection is. Among some United States' ethnic groups, however, HBV is a more common risk factor than HCV. For example, a report from Los Angeles found that 74% of HCC among Asians was linked to HBV, while 90% of HCC in whites was linked to HCV.9
The etiology of HCC is likely to involve interactions between multiple risk factors. In a study which utilized the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases,12 the most commonly reported risk-factor was nonspecific cirrhosis (21%), followed by alcohol-induced liver disease (16%), HCV infection (10%), and HBV infection (5%). Obesity and type II diabetes6 are also suspected to increase risk.
To monitor changes in the burden of HCC in the United States, this report provides analyses of incidence and survival of HCC and mortality of liver cancer. To define at-risk populations, data were examined by sex, race/ethnicity, and age.
RESULTS
Age-Adjusted HCC Incidence Data
Overall age-adjusted incidence rates of HCC tripled between 1975 and 2005, rising from 1.6 per 100,000 to 4.9 per 100,000 (Fig 1). Incidence rates were approximately three times higher among men than among women throughout this time period. The best fitting model for overall HCC incidence trends had two segments. The first segment, from 1975 to 1980, showed no change in HCC incidence. The second segment, fitting HCC incidence trends from 1980 to 2005, estimated an annual percent change of 4.5% (P ≤ .05). When rates among males and females were modeled separately, the best-fitting joinpoint models had one segment. The annual percent changes in HCC incidence from 1975 to 2005 were statistically significant in both models (P ≤ .05).
Birth Cohort Analyses
Examining age-specific incidence by birth cohort revealed that rates increased in each successive birth cohort born between 1900 and 1959 (Fig 2). Incidence rates for the most recent surveillance years (marked with asterisks) were not adjusted for delayed reporting or final cases in the last birth years of each cohort.
Age-Adjusted Rates by Race and Ethnicity
Between 1992 and 2005, overall incidence rates of HCC increased, with an annual percent change of 4.3% (P ≤ .05; Table 1). Asians/Pacific Islanders had the highest age-adjusted HCC incidence rates throughout the period, followed by Hispanics, blacks, American Indians/Alaska Natives and whites (Table 1). Although Asians/Pacific Islanders had the highest incidence, they experienced a smaller annual percent change in HCC incidence rates (annual percent change [APC] = 1.0%) than other racial/ethnic groups. American Indians/Alaska Natives experienced the greatest significant increase (APC = 5.0%), followed by blacks (APC = 4.9%), whites (APC = 4.6%), and Hispanics (APC = 4.0%). For each trend, the best-fitting joinpoint model had one segment.
Table 1. Age-Adjusted HCC Incidence Rates, Liver Cancer Death Rates, and 1-Year Cause-Specific Survival Rates for HCC, From 1992 to 2005 by Time Period and Race/Ethnicity, With APC
United States Versus Foreign Place of Birth
Data on place of birth were available for 81% of persons with HCC diagnosed in the SEER 13 registries between 2000 and 2005, including more than 80% of patients in all racial groups and 77% of Hispanic patients (data not shown). Among patients with data, 31% were born outside the United States; however, 80% of Asians/Pacific Islanders with data were born outside the United States, more than any other racial or ethnic group. Among Hispanics with HCC, 40% were born outside the United States. Compared with Asian/Pacific Islander and Hispanic HCC cases, foreign birth occurred less frequently among white (17%), black (6%), and American Indian/Alaska Native HCC patients (3%) with data.
Recent Incidence Trends
An examination of age-specific HCC incidence rates in SEER 13 registries in 2000 to 2002 and 2003 to 2005 revealed marked increases in incidence rates among men 50 to 59 years of age and 75 to 84 years of age (Fig 3) with slight increases in incidence rates among women in these age groups.
Within the 50- to 59-year age group, the annual percent change in HCC incidence rates significantly increased from 2000 to 2005 for Hispanic men, black men, and white men, and for black and white women (P ≤ .05), with HCC incidence rates among blacks exceeding those of Asians/Pacific Islanders during 2003 to 2005 (Table 2). Among persons 75 to 84 years of age, increases in HCC incidence were seen among all men and white women (P ≤ .05). No other significant annual percent changes were seen from 2000 to 2005 by age, sex, or race/ethnicity (data not shown).
Age-Adjusted Liver Cancer Mortality Data
Between 1992 and 2005, patterns in liver cancer mortality were similar to patterns in HCC incidence. Overall age-adjusted mortality rates increased, with an annual percent change of 1.6% (P ≤ .05). Mortality rates were highest for Asians/Pacific Islanders, followed by Hispanics, blacks, American Indians/Alaska Natives, and finally whites (Table 1). Rates increased significantly among Hispanics and whites (APC = 1.7%) as well as blacks (APC = 1.3%). Mortality rates among Asians/Pacific Islanders, however, significantly declined (APC = –0.9%), with stable mortality rates among American Indian/Alaska Native populations.
Survival Rates
One-year cause-specific survival rates increased over time for all racial/ethnic groups except American Indians/Alaska Natives (Table 1). During the recent years, 2003 to 2004, the overall 1-year survival rate was 47% (range, 40% for blacks to 49% for Asian/Pacific Islanders).
Overall, survival rates increased for short, intermediate, and longer-term follow-up intervals over the time period of study, with a doubling of 2- to 4-year cause-specific survival rates (Table 3). These increases in survival rates occurred as more patients were diagnosed with localized stage HCC (28% in 1992 to 1993, 44% in 2003 to 2004) and 1-year survival rates for patients with localized HCC increased from 41% to 67%. Among patients with localized HCC that reported therapy, 1-year survival rates increased from 65% in 1992 to 1993 to 83% in 2003 to 2004. One-year survival rates for patients with localized HCC who received surgery increased from 81% to 91% between 1992 to 1993 and 2003 to 2004 (data not shown). Survival rates also increased among patients with regional HCC who reported therapy. Although changes in survival rates for cases with distant HCC were less pronounced, patients reporting treatment had higher survival rates.
DISCUSSION
The principal findings in this report were that incidence rates of HCC tripled in the United States from 1975 through 2005, with marked recent increases among middle-aged black, Hispanic, and white males; there was a birth-cohort effect on risk; and overall 1-year cause-specific survival rates for new HCC patients nearly doubled from 1992 to 2004 as more patients were diagnosed with low-stage HCC and their prognosis improved. Increases in cause-specific survival rates were experienced by all racial and ethnic groups, except for American Indians/Alaska Natives. However, despite increasing HCC survival rates, improvement is needed, with the 1-year cause-specific survival rate remaining lower than 50%.
Much of the increase in incidence between 2000 and 2005 occurred among men age 50 to 59 years. Not all racial/ethnic groups were equally affected, with black, Hispanic, and white men experiencing the greatest increases. Between 2003 and 2005, for both sexes, blacks in this age group had higher incidence rates than Asian/Pacific Islanders. The changing racial pattern of HCC in this age group may be partially attributable to an epidemic of HCV infection that occurred approximately four decades earlier, in the 1960s, when they were young adults.10 Several findings in this report suggest, however, that risk of HCC is likely to be driven by additional factors. There has been a steady increase in age-adjusted HCC incidence rates among men and women since 1975. Age-specific rates have increased in each successive birth cohort between 1900 and 1959. Etiologic studies of recent HCC patients are recommended to elucidate factors contributing to the ongoing increase in HCC incidence.
In contrast with other racial groups, most Asians/Pacific Islanders with HCC were born outside the United States. This predominance of foreign births is consistent with HBV infection being a major risk factor among most groups of Asians/Pacific Islanders9,20 as chronic HBV infection is notably more common in eastern Asian countries than in the United States, with higher HCC incidence rates among Southeast Asians compared with Filipinos, Japanese, and Asian Indians/Pakistanis.19 An exception is Japan, where more HCC patients are linked to HCV infection than HBV infection.21 The modest increase in HCC incidence rates and decrease in liver cancer mortality rates from 1992 to 2005 suggests that Asians/Pacific Islander populations born in the United States have, thus far, not been as affected by the factors that are driving the HCC increases in other populations. Worldwide, the incidence of HCC among Asians/Pacific Islanders is likely to decline as HBV vaccination becomes more widespread in Asian countries.22
In this study, HCC incidence rates among Hispanics were lower than among Asians/Pacific Islanders, but higher than among whites. Approximately one half of Hispanic HCC patients were born in the United States. In contrast to Asians/Pacific Islanders, HCC incidence rates are reported to be higher among Hispanics born in the United States than among foreign-born Hispanics.23 This suggests that factors associated with life in the United States, perhaps including HCV infection,10 alcohol abuse,24 or obesity,25 may be adversely affecting Hispanic populations.
Despite a paucity of new therapies for HCC during the surveillance years in this report, 1-year cause-specific survival rates for HCC nearly doubled between 1992 to 1993 and 2003 to 2004. This supports earlier evidence that survival rates for HCC are increasing.26 Initially, the increase in survival was restricted to short-term follow-up27; however, in this report 4-year survival rates doubled and 5-year survival rates increased by more than 60%. Furthermore, more patients were diagnosed with localized and regional stage HCC and survival rates increased for these patients. With greater awareness of HCC, more patients are being diagnosed with asymptomatic disease via active screening employing serum alpha-fetoprotein testing, abdominal ultrasound, and diagnostic imaging.28 Furthermore, aggressive treatments including transplantation and resection of localized-stage tumors appear to be improving long-term survival.29 The advent of targeted HCC therapies holds promise for further improvement in prognosis among patients with regional and distant-stage HCC.30
Racial variation was seen in 1-year cause-specific survival rates. In 2003 to 2004, survival was greatest among Asians/Pacific Islanders (49%) and lowest among blacks (40%) and American Indians/Alaska Natives (41%). In another study, racial and ethnic variations in survival were partially explained by stage at diagnosis and the therapy received by blacks and Hispanics compared with whites.26 While improvements in survival are needed across all racial and ethnic groups, blacks and American Indians/Alaska Natives may particularly benefit from targeted HCC control efforts.
Coordination of existing HCC prevention efforts is needed. Primary HCC prevention measures include hepatitis B vaccination programs,22 screening of the blood supply for hepatitis viruses,31 and campaigns to discourage intravenous drug abuse. Secondary prevention measures focus on detecting asymptomatic HCC among at-risk individuals28 through periodic screening of high-risk patients by ultrasound, with follow-up tests when suspicious lesions are detected.32 High-risk individuals include cirrhotic patients, adult HBV carriers, and persons infected with HCV. Gaps in HCC screening in the United States include limited HCV testing of current and former injected drug users,33 pre-1990 transfusion recipients,34 and incomplete HBV testing of foreign-born Asians/Pacific Islanders.35 In addition, cultural and economic barriers to HCC screening of chronic viral carriers exist.36,37 Tertiary measures for HCC vary by stage of disease and comorbidity but include surgical resection, transplantation, radiofrequency ablation, and chemoembolization.28 A SEER-Medicare linked study of HCC patients diagnosed in the 1990s indicated that only one third of cases with favorable tumor features received potentially curative therapy.38
A limitation of this study is the absence of information on risk factors. There is a need for studies to estimate the current proportion of HCCs that are attributed to HCV and to HBV including differences across demographic groups.9,39 Studies are needed of the oncogenic potential of viral genotypes.40,41 Associations with suspected cofactors for HCC should also be examined, including alcoholism24 and steatohepatitis,25 obesity,42 diabetes mellitus,43 and iron storage diseases.44
This report may underestimate recent increases in HCC incidence rates because of delays in reporting16 and an estimated rate of under-reporting of 2.5% because of absence of data on Veterans' Affairs hospital patients,5 a population which may be at elevated risk for HCC compared with the general population.45 Despite these limitations, the findings strongly suggest that HCC incidence and mortality continue to increase in the United States. In addition, this report provides reason for optimism that, with more HCC screening of high-risk groups and treatment of low-stage disease, the burden of HCC can be lessened.
"The principal findings in this report were that incidence rates of HCC tripled in the United States from 1975 through 2005, with marked recent increases among middle-aged black, Hispanic, and white males"
"Overall age-adjusted incidence rates of HCC tripled between 1975 and 2005, rising from 1.6 per 100,000 to 4.9 per 100,000.....Between 1992 and 2005, overall incidence rates of HCC increased, with an annual percent change of 4.3% (P ≤ .05).....American Indians/Alaska Natives experienced the greatest significant increase (APC = 5.0%), followed by blacks (APC = 4.9%), whites (APC = 4.6%), and Hispanics (APC = 4.0%), look at Table 1 below and you'll much higher incidence rates among Blacks & Hispanics compared to whites, the affects are disproportionate in terms of having HCC and deaths due to HCC (from Jules: this is likely to worse access to care, poor treatment decision making, and undiagnosed HCV/HBV and HCC........(from Jules: there is little or no HCV screening and screening for HCC. There is no Federal support for national screening and surveillance of HCV)......Coordination of existing HCC prevention efforts is needed. Gaps in HCC screening in the United States include limited HCV testing of current and former injected drug users,33 pre-1990 transfusion recipients,34 and incomplete HBV testing of foreign-born Asians/Pacific Islanders.35 In addition, cultural and economic barriers to HCC screening of chronic viral carriers existMuch of the increase in incidence between 2000 and 2005 occurred among men age 50 to 59 years. Not all racial/ethnic groups were equally affected, with black, Hispanic, and white men experiencing the greatest increases.....The changing racial pattern of HCC in this age group may be partially attributable to an epidemic of HCV infection that occurred approximately four decades earlier, in the 1960s, when they were young adults.10 Several findings in this report suggest, however, that risk of HCC is likely to be driven by additional factors.....HCC incidence rates are reported to be higher among Hispanics born in the United States than among foreign-born Hispanics.23 This suggests that factors associated with life in the United States, perhaps including HCV infection,10 alcohol abuse,24 or obesity,25 may be adversely affecting Hispanic populations. here is a need for studies to estimate the current proportion of HCCs that are attributed to HCV and to HBV including differences across demographic groups.9,39..... Associations with suspected cofactors for HCC should also be examined, including alcoholism24 and steatohepatitis,25 obesity,42 diabetes mellitus,43 and iron storage diseases.44.....This report may underestimate recent increases in HCC incidence rates because of delays in reporting16 and an estimated rate of under-reporting of 2.5% because of absence of data on Veterans' Affairs hospital patients,5 a population which may be at elevated risk for HCC compared with the general population"
Hepatocellular Carcinoma Incidence, Mortality, and Survival Trends in the United States From 1975 to 2005
Sean F. Altekruse, Katherine A. McGlynn, Marsha E. Reichman
From the Division of Cancer Control and Population Sciences, and the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Corresponding author: Sean F. Altekruse, DVM, MPH, PhD, Cancer Statistics Branch, Division of Cancer Control and Population Sciences, National Cancer Institute, 6116 Executive Blvd Suite 504, Bethesda, MD 20892-8316; e-mail: altekrusesf@mail.nih.gov.
ABSTRACT
Purpose - Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Incidence rates are increasing in the United States. Monitoring incidence, survival, and mortality rates within at-risk populations can facilitate control efforts.
Methods - Age-adjusted incidence trends for HCC were examined in the Surveillance, Epidemiology, and End Results (SEER) registries from 1975 to 2005. Age-specific rates were examined for birth cohorts born between 1900 and 1959. Age-adjusted incidence and cause-specific survival rates from 1992 to 2005 were examined in the SEER 13 registries by race/ethnicity, stage, and treatment. United States liver cancer mortality rates were also examined.
Results - Age-adjusted HCC incidence rates tripled between 1975 and 2005. Incidence rates increased in each 10-year birth cohort from 1900 through the 1950s. Asians/Pacific Islanders had higher incidence and mortality rates than other racial/ethnic groups, but experienced a significant decrease in mortality rates over time. From 2000 to 2005, marked increases in incidence rates occurred among Hispanic, black, and white middle-aged men. Between 1992 and 2004, 2- to 4-year HCC survival rates doubled, as more patients were diagnosed with localized and regional HCC and prognosis improved, particularly for patients with reported treatment. Recent 1-year survival rates remained, however, less than 50%.
Conclusion - HCC incidence and mortality rates continue to increase, particularly among middle-aged black, Hispanic, and white men. Screening of at-risk groups and treatment of localized-stage tumors may contribute to increasing HCC survival rates in the United States. More progress is needed.
INTRODUCTION
Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide.1 This malignancy occurs more often among men than women, with the highest incidence rates reported in East Asia.2 The incidence rates of HCC in the United States have historically been lower than in many countries. However, in recent decades, HCC age-adjusted incidence rates have doubled3 and primary liver cancer mortality rates have increased faster than mortality rates for any other leading cause of cancer.4,5 Approximately 90% of primary liver cancers in the United States are HCCs, while most of the remaining 10% are intrahepatic cholangiocarcinomas.6 The pathway leading to HCC generally begins with an acute hepatic insult which progresses over decades. Fibrosis and cirrhosis are typically precursors of HCC.7 Among patients with localized stage HCC, treatment options may include resection or transplantation. Chemoembolization, a combination of chemotherapy and occlusion of the tumor blood supply, is reported to improve survival in well-selected patients with unresectable HCC.8 Many patients who are diagnosed with HCC, however, have advanced disease and are only candidates for palliative care, contributing to a relatively low reported 5-year survival rate of approximately 10%.6
Most HCC is thought to be associated with either chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection.9 In the United States, more than 3 million people are chronically infected with HCV.10 Many of these individuals were exposed as young adults beginning in the 1960s.10,11 HCV risk factors include contaminated blood product transfusion and injected drug use.10,11
Chronic infection with HBV, a major global risk factor for HCC, is less common overall in the United States than HCV infection is. Among some United States' ethnic groups, however, HBV is a more common risk factor than HCV. For example, a report from Los Angeles found that 74% of HCC among Asians was linked to HBV, while 90% of HCC in whites was linked to HCV.9
The etiology of HCC is likely to involve interactions between multiple risk factors. In a study which utilized the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases,12 the most commonly reported risk-factor was nonspecific cirrhosis (21%), followed by alcohol-induced liver disease (16%), HCV infection (10%), and HBV infection (5%). Obesity and type II diabetes6 are also suspected to increase risk.
To monitor changes in the burden of HCC in the United States, this report provides analyses of incidence and survival of HCC and mortality of liver cancer. To define at-risk populations, data were examined by sex, race/ethnicity, and age.
RESULTS
Age-Adjusted HCC Incidence Data
Overall age-adjusted incidence rates of HCC tripled between 1975 and 2005, rising from 1.6 per 100,000 to 4.9 per 100,000 (Fig 1). Incidence rates were approximately three times higher among men than among women throughout this time period. The best fitting model for overall HCC incidence trends had two segments. The first segment, from 1975 to 1980, showed no change in HCC incidence. The second segment, fitting HCC incidence trends from 1980 to 2005, estimated an annual percent change of 4.5% (P ≤ .05). When rates among males and females were modeled separately, the best-fitting joinpoint models had one segment. The annual percent changes in HCC incidence from 1975 to 2005 were statistically significant in both models (P ≤ .05).
Birth Cohort Analyses
Examining age-specific incidence by birth cohort revealed that rates increased in each successive birth cohort born between 1900 and 1959 (Fig 2). Incidence rates for the most recent surveillance years (marked with asterisks) were not adjusted for delayed reporting or final cases in the last birth years of each cohort.
Age-Adjusted Rates by Race and Ethnicity
Between 1992 and 2005, overall incidence rates of HCC increased, with an annual percent change of 4.3% (P ≤ .05; Table 1). Asians/Pacific Islanders had the highest age-adjusted HCC incidence rates throughout the period, followed by Hispanics, blacks, American Indians/Alaska Natives and whites (Table 1). Although Asians/Pacific Islanders had the highest incidence, they experienced a smaller annual percent change in HCC incidence rates (annual percent change [APC] = 1.0%) than other racial/ethnic groups. American Indians/Alaska Natives experienced the greatest significant increase (APC = 5.0%), followed by blacks (APC = 4.9%), whites (APC = 4.6%), and Hispanics (APC = 4.0%). For each trend, the best-fitting joinpoint model had one segment.
Table 1. Age-Adjusted HCC Incidence Rates, Liver Cancer Death Rates, and 1-Year Cause-Specific Survival Rates for HCC, From 1992 to 2005 by Time Period and Race/Ethnicity, With APC
United States Versus Foreign Place of Birth
Data on place of birth were available for 81% of persons with HCC diagnosed in the SEER 13 registries between 2000 and 2005, including more than 80% of patients in all racial groups and 77% of Hispanic patients (data not shown). Among patients with data, 31% were born outside the United States; however, 80% of Asians/Pacific Islanders with data were born outside the United States, more than any other racial or ethnic group. Among Hispanics with HCC, 40% were born outside the United States. Compared with Asian/Pacific Islander and Hispanic HCC cases, foreign birth occurred less frequently among white (17%), black (6%), and American Indian/Alaska Native HCC patients (3%) with data.
Recent Incidence Trends
An examination of age-specific HCC incidence rates in SEER 13 registries in 2000 to 2002 and 2003 to 2005 revealed marked increases in incidence rates among men 50 to 59 years of age and 75 to 84 years of age (Fig 3) with slight increases in incidence rates among women in these age groups.
Within the 50- to 59-year age group, the annual percent change in HCC incidence rates significantly increased from 2000 to 2005 for Hispanic men, black men, and white men, and for black and white women (P ≤ .05), with HCC incidence rates among blacks exceeding those of Asians/Pacific Islanders during 2003 to 2005 (Table 2). Among persons 75 to 84 years of age, increases in HCC incidence were seen among all men and white women (P ≤ .05). No other significant annual percent changes were seen from 2000 to 2005 by age, sex, or race/ethnicity (data not shown).
Age-Adjusted Liver Cancer Mortality Data
Between 1992 and 2005, patterns in liver cancer mortality were similar to patterns in HCC incidence. Overall age-adjusted mortality rates increased, with an annual percent change of 1.6% (P ≤ .05). Mortality rates were highest for Asians/Pacific Islanders, followed by Hispanics, blacks, American Indians/Alaska Natives, and finally whites (Table 1). Rates increased significantly among Hispanics and whites (APC = 1.7%) as well as blacks (APC = 1.3%). Mortality rates among Asians/Pacific Islanders, however, significantly declined (APC = –0.9%), with stable mortality rates among American Indian/Alaska Native populations.
Survival Rates
One-year cause-specific survival rates increased over time for all racial/ethnic groups except American Indians/Alaska Natives (Table 1). During the recent years, 2003 to 2004, the overall 1-year survival rate was 47% (range, 40% for blacks to 49% for Asian/Pacific Islanders).
Overall, survival rates increased for short, intermediate, and longer-term follow-up intervals over the time period of study, with a doubling of 2- to 4-year cause-specific survival rates (Table 3). These increases in survival rates occurred as more patients were diagnosed with localized stage HCC (28% in 1992 to 1993, 44% in 2003 to 2004) and 1-year survival rates for patients with localized HCC increased from 41% to 67%. Among patients with localized HCC that reported therapy, 1-year survival rates increased from 65% in 1992 to 1993 to 83% in 2003 to 2004. One-year survival rates for patients with localized HCC who received surgery increased from 81% to 91% between 1992 to 1993 and 2003 to 2004 (data not shown). Survival rates also increased among patients with regional HCC who reported therapy. Although changes in survival rates for cases with distant HCC were less pronounced, patients reporting treatment had higher survival rates.
DISCUSSION
The principal findings in this report were that incidence rates of HCC tripled in the United States from 1975 through 2005, with marked recent increases among middle-aged black, Hispanic, and white males; there was a birth-cohort effect on risk; and overall 1-year cause-specific survival rates for new HCC patients nearly doubled from 1992 to 2004 as more patients were diagnosed with low-stage HCC and their prognosis improved. Increases in cause-specific survival rates were experienced by all racial and ethnic groups, except for American Indians/Alaska Natives. However, despite increasing HCC survival rates, improvement is needed, with the 1-year cause-specific survival rate remaining lower than 50%.
Much of the increase in incidence between 2000 and 2005 occurred among men age 50 to 59 years. Not all racial/ethnic groups were equally affected, with black, Hispanic, and white men experiencing the greatest increases. Between 2003 and 2005, for both sexes, blacks in this age group had higher incidence rates than Asian/Pacific Islanders. The changing racial pattern of HCC in this age group may be partially attributable to an epidemic of HCV infection that occurred approximately four decades earlier, in the 1960s, when they were young adults.10 Several findings in this report suggest, however, that risk of HCC is likely to be driven by additional factors. There has been a steady increase in age-adjusted HCC incidence rates among men and women since 1975. Age-specific rates have increased in each successive birth cohort between 1900 and 1959. Etiologic studies of recent HCC patients are recommended to elucidate factors contributing to the ongoing increase in HCC incidence.
In contrast with other racial groups, most Asians/Pacific Islanders with HCC were born outside the United States. This predominance of foreign births is consistent with HBV infection being a major risk factor among most groups of Asians/Pacific Islanders9,20 as chronic HBV infection is notably more common in eastern Asian countries than in the United States, with higher HCC incidence rates among Southeast Asians compared with Filipinos, Japanese, and Asian Indians/Pakistanis.19 An exception is Japan, where more HCC patients are linked to HCV infection than HBV infection.21 The modest increase in HCC incidence rates and decrease in liver cancer mortality rates from 1992 to 2005 suggests that Asians/Pacific Islander populations born in the United States have, thus far, not been as affected by the factors that are driving the HCC increases in other populations. Worldwide, the incidence of HCC among Asians/Pacific Islanders is likely to decline as HBV vaccination becomes more widespread in Asian countries.22
In this study, HCC incidence rates among Hispanics were lower than among Asians/Pacific Islanders, but higher than among whites. Approximately one half of Hispanic HCC patients were born in the United States. In contrast to Asians/Pacific Islanders, HCC incidence rates are reported to be higher among Hispanics born in the United States than among foreign-born Hispanics.23 This suggests that factors associated with life in the United States, perhaps including HCV infection,10 alcohol abuse,24 or obesity,25 may be adversely affecting Hispanic populations.
Despite a paucity of new therapies for HCC during the surveillance years in this report, 1-year cause-specific survival rates for HCC nearly doubled between 1992 to 1993 and 2003 to 2004. This supports earlier evidence that survival rates for HCC are increasing.26 Initially, the increase in survival was restricted to short-term follow-up27; however, in this report 4-year survival rates doubled and 5-year survival rates increased by more than 60%. Furthermore, more patients were diagnosed with localized and regional stage HCC and survival rates increased for these patients. With greater awareness of HCC, more patients are being diagnosed with asymptomatic disease via active screening employing serum alpha-fetoprotein testing, abdominal ultrasound, and diagnostic imaging.28 Furthermore, aggressive treatments including transplantation and resection of localized-stage tumors appear to be improving long-term survival.29 The advent of targeted HCC therapies holds promise for further improvement in prognosis among patients with regional and distant-stage HCC.30
Racial variation was seen in 1-year cause-specific survival rates. In 2003 to 2004, survival was greatest among Asians/Pacific Islanders (49%) and lowest among blacks (40%) and American Indians/Alaska Natives (41%). In another study, racial and ethnic variations in survival were partially explained by stage at diagnosis and the therapy received by blacks and Hispanics compared with whites.26 While improvements in survival are needed across all racial and ethnic groups, blacks and American Indians/Alaska Natives may particularly benefit from targeted HCC control efforts.
Coordination of existing HCC prevention efforts is needed. Primary HCC prevention measures include hepatitis B vaccination programs,22 screening of the blood supply for hepatitis viruses,31 and campaigns to discourage intravenous drug abuse. Secondary prevention measures focus on detecting asymptomatic HCC among at-risk individuals28 through periodic screening of high-risk patients by ultrasound, with follow-up tests when suspicious lesions are detected.32 High-risk individuals include cirrhotic patients, adult HBV carriers, and persons infected with HCV. Gaps in HCC screening in the United States include limited HCV testing of current and former injected drug users,33 pre-1990 transfusion recipients,34 and incomplete HBV testing of foreign-born Asians/Pacific Islanders.35 In addition, cultural and economic barriers to HCC screening of chronic viral carriers exist.36,37 Tertiary measures for HCC vary by stage of disease and comorbidity but include surgical resection, transplantation, radiofrequency ablation, and chemoembolization.28 A SEER-Medicare linked study of HCC patients diagnosed in the 1990s indicated that only one third of cases with favorable tumor features received potentially curative therapy.38
A limitation of this study is the absence of information on risk factors. There is a need for studies to estimate the current proportion of HCCs that are attributed to HCV and to HBV including differences across demographic groups.9,39 Studies are needed of the oncogenic potential of viral genotypes.40,41 Associations with suspected cofactors for HCC should also be examined, including alcoholism24 and steatohepatitis,25 obesity,42 diabetes mellitus,43 and iron storage diseases.44
This report may underestimate recent increases in HCC incidence rates because of delays in reporting16 and an estimated rate of under-reporting of 2.5% because of absence of data on Veterans' Affairs hospital patients,5 a population which may be at elevated risk for HCC compared with the general population.45 Despite these limitations, the findings strongly suggest that HCC incidence and mortality continue to increase in the United States. In addition, this report provides reason for optimism that, with more HCC screening of high-risk groups and treatment of low-stage disease, the burden of HCC can be lessened.
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