HBV Vaccination Cuts Liver Cancer Risk

HBV Vaccination Cuts Liver Cancer Risk
By Charles Bankhead, Staff Writer, MedPage Today
Published: September 17, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
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Newborns vaccinated against hepatitis B infection had almost a 70% lower risk of hepatocellular carcinoma through early adulthood compared with an unvaccinated cohort, Taiwanese investigators reported.

Failure to control maternal HBV infection accounted for 95% of the cases of hepatocellular carcinoma in the vaccinated cohort, according to an article published online in the Journal of the National Cancer Institute.

"These data revealed that prenatal maternal HBsAG [hepatitis B surface antigen] status is the key factor affecting chronic HBV infection and hence hepatocellular carcinoma development," said Mei-Hwei Chang, MD, of Taiwan University Hospital in Taipei, and co-authors. "Vaccine failure and poor compliance with the HBV immunization protocol are the two most important causes of failure to block HBV transmission to children from high-risk mothers."

"Maternal transmission of HBV could not be eradicated by the current HBV immunization program," they added. "Further efforts to completely interrupt maternal transmission are crucial in eradicating HBV-related hepatocellular carcinoma."

Because the study did not consider factors other than HBV in liver cancer etiology, the authors cautioned against "concluding that HBV vaccination is the only factor contributing to the reduction of hepatocellular carcinoma."

In areas of endemic HBV infection, as many as 80% of adults with hepatocellular carcinoma are seropositive for HBsAg, and the cancer also occurs in children in areas of endemic infection. The authors previously reported near-100% seropositivity for HBsAg in children with hepatocellular carcinoma, as well as integration of HBV DNA into the host genome of tumor tissue (Cancer 1989; 64(11): 2377-80; Hepatology 1991; 13(2): 316-20).

In 1984, Taiwan implemented a universal HBV immunization program, which has been associated with a substantial decline in the incidence of liver cancer in children, the authors said.

Because most cases occur in people 40 and older, the vaccine's ability to protect against liver cancer beyond childhood is essential, they noted. Toward that end, they examined incidence in vaccinated and unvaccinated cohorts.

Review of two national cancer registries identified 1,958 cases of hepatocellular carcinoma diagnosed from 1983 through 2004 in Taiwan residents ages 6 to 29.

Among patients vaccinated after implementation of the universal HBV vaccination program (ages 6 to 19), investigators identified 64 cases from 37,709,304 person-years of follow-up. That compared with 444 cases in 78,496,406 person-years in unvaccinated patients.

The difference between cohorts translated into an age- and sex-adjusted relative risk of 0.31 for hepatocellular cancer in vaccinated versus unvaccinated patients (P<0.001).

Among vaccinated patients the risk of developing hepatocellular carcinoma was significantly associated with

* Incomplete vaccination (OR 4.32, 95% CI 2.34 to 7.91 for fewer than three doses of vaccine)
* Prenatal maternal HBsAg seropositivity (OR 29.5, 95% CI 13.98 to 62.6)
* Prenatal maternal seropositivity for hepatitis B envelope antigen (OR 5.13, 95% CI 2.24 to 11.71 with administration of HBV immunoglobulin at birth, and OR 9.43, 95% CI 3.54 to 25.11 without immunoglobulin administration)

A limitation of the study noted by the authors was the fact that the role of host factors, including genetic polymorphisms, was not studied, so the interpretation of data could have been affected.

The study was funded by the National Health Research Institutes of Taiwan.

The authors had no disclosures relevant to the study.

Primary source: Journal of the National Cancer Institute
Source reference:
Chang M-H, et al "Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study" J Natl Cancer Inst 2009; DOI: 10.1093/jnci/djp288.