HEPNews The Hepatitis Education Project Newsletter

HEPNews
The Hepatitis Education Project Newsletter
Volume 15, Number 4
Winter 2009
Phone (206) 732-0311
http://www.hepeducation.org
HepInfo@hepeducation.org
911 Western Ave #302
Seattle, WA 98104
(Continued on Pg.7)
Supporting HEP’s Work
ATLANTA, 12/7/09
U.S. Representative Hank Johnson is
battling Hepatitis C. With his announcement
today, he is believed to be the first
sitting Member of Congress to acknowledge
that he is living with hepatitis C.
The Georgia Congressman released the
following statement:
“Over the past year, I have been on a
robust course of treatment for hepatitis C
(HCV), a virus that affects more than four
million Americans. I am pleased to announce
that my therapy is progressing
well. My physician is encouraged by my
response to treatment and expects complete
success eradicating the virus.
I hope that my disclosure will provide
others suffering from HCV with confidence
to speak out and educate the community
about this illness. Through clinical
trials and medical research, we must
always seek new, more effective treatments.
I plan to use my position as a public
figure to raise awareness of the consequences
of this infection and let others
fighting hepatitis know that it is possible
to succeed and excel while battling this
disease.
The causes of this disease are many,
but in the end it does not matter how someone
contracted the virus. Like so many
millions of others, I was infected many
years without ever knowing how I contracted
it.
In fact, more than half the people who
have hepatitis C don’t know how or when
they contracted it. And many are fearful
of the treatment regimen that impacts your
life in unusual ways. Having come through
a long course of treatment, I want to send
a strong message that a cure is possible
but you must be tested and treated.
I will be working with the National
Viral Hepatitis Roundtable (NVHR) to
help educate my colleagues and the public
to learn more about this largely misunderstood
disease. It is treatable, but we
must devote the will and resources it deserves
in light of the urgent need.
Though this infection has caused me
some discomfort and frustration, it has in
US Congressman Battling Hepatitis C
At this time of year many of us consider
how we can support the many causes
that are asking us for help. In these difficult
economic times, we are making tough
choices between important and pressing
priorities for our money. We ask that you
make HEP’s work a priority for yourself.
As patients, family members, and health
care professionals who read HEPNews,
we have all seen the damage that this epidemic
is doing on a personal level. If we
won’t help, who will?
HEP has continued to grow and change
this past year – it’s been our most productive
year to date. With our new fulltime
program coordinator, Maureen Oscadal,
we have been expanding programs and
developing new programs across our region.
Some of those programs include a
national support hotline; free hepatitis C
testing; educational programs for public
health, community groups and corrections;
advocacy at the local, state and federal
levels; and operation of the only walkin
resource center for hepatitis patients in
the Pacific Northwest.
Many of our activities are funded by
grants and contracts. But there remains a
core of services that rely on private donations
for their funding. Most important of
these right now is the development of prototype
programs that can be then submitted
for funding once they have been tested
and shown to be successful. Private donations
are extremely important for getting
such programs started.
Some of our programs in development
are focused on youth, harm reduction,
drug treatment centers, and homeless
women and men. Beginning in 2010, we
also plan to offer free hepatitis A and B
vaccination.
You can help build these programs by
giving to HEP. The epidemic is growing,
and HEP has to grow too. Support from
you is critical – please look over our donation
form on the back of this newsletter
and see how you can help. Thank you for
making it possible for HEP to make a difference.
Please contact me with your
thoughts at sngraham@hepeducation.org.
Steve Graham - President HEP
The support group that normally
meets at the HEP office on the last
Saturday of the month has been
rescheduled this month and will
take place at HEP on Saturday,
Dec. 19th from 10-11:30am.
- David Johnston, group leader
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Did pegylated interferon+ribavirin
treatment for hepatitis C not work for you,
or were you unable to tolerate treatment?
The Digestive Disease Institute at Virginia
Mason Medical Center is conducting a
study of a drug called a caspase inhibitor,
which may reduce liver scarring from
hepatitis C. If you join this study, you
would be randomized to the study drug
or a placebo for 6 months, and would have
two liver biopsies, one at the beginning
and one at the end of the study period.
Individuals with genotype 3 or who have
taken milk thistle within the past 3 months
are not eligible for this study.
If interested, please call the study coordinator
Alice Stead at 206 341-1450.
Do you have hepatitis C? Is your platelet
count low, making it difficult for you
to take pegylated interferon + ribavirin
therapy? The Digestive Disease Institute
is conducting a study using a new drug
called Eltrombopag, which may raise your
platelet count and make it possible to tolerate
interferon treatment for hepatitis C.
Individuals with platelet counts < 75,000
are eligible. Individuals who have completed
full-dose therapy with pegylated interferon
and who did not respond are not
eligible, but if treatment had to be discontinued
or dose-reduced because of low
platelet count, then study participation
may be possible.
If interested, please call the study coordinator,
Cherly Saunders – 206-341-
1786.
1 in 5 Hepatitis C Patients Receiving Antiviral Therapy
November 24, 2009
Washington, DC—New peer-reviewed
data finding that fewer than one-fifth of
the nearly 4 million Americans infected
with chronic hepatitis C virus have received
anti-viral therapy in recent years
should be a wake-up call that Congress
needs to move urgently on bipartisan legislation
to support new state-based detection,
research, and surveillance efforts, the
National Viral Hepatitis Roundtable
(NVHR) said today.
The NVHR warns that without congressional
action, millions of Americans
infected with chronic hepatitis C virus –
particularly African Americans – are at
serious risk of developing cirrhosis, liver
cancer, and liver failure and will add billions
of dollars in unnecessary costs to our
health care system every year.
The NVHR is a coalition of more than
150 public, private, and voluntary organizations
dedicated to reducing the incidence
of infection, morbidity, and mortality
from viral hepatitis in the United
States through strategic planning, leadership,
coordination, advocacy, and research.
www.nvhr.org
“These shocking data should serve as
a wake-up call that current public-health
detection, treatment, and surveillance efforts
for chronic hepatitis C viral infection
are wholly inadequate,” said NVHR
Chair Lorren Sandt. “In terms of detection
and treatment, the proverbial lowhanging
fruit has been picked. In order to
help our system reach under-served populations,
Congress needs to act now on the
bipartisan Honda-Dent legislation. Without
action from Washington to support
state-based efforts, millions of Americans
will suffer from severe hepatitis-related
complications and cost our health system
tens of billions of dollars annually in
avoidable medical costs.”
The alarming research trends identified
in the new study were conducted by researchers
at the University of Michigan
and published in the December issue of
Hepatology, a journal of the American
Association for the Study of Liver Diseases
(AASLD). Among the key findings:
November 24, 2009
•Only about 663,000 of the estimated
3.9 million Americans infected with
chronic hepatitis C virus received antiviral
therapy between 2002 and 2007;
•Treatment rates appear to be declining
in part because only one-half of all
HCV patients know they are infected;
•Barriers to HCV screening including
the absence of health insurance coverage,
limited access to standard medical care,
and lower priority of HCV testing by primary
care physicians; and
•Increased public health efforts are
needed to improve access to antiviral
therapy and the researchers recommend
further research of health services delivery
and quality of care for HCV patients.
Last month, bipartisan legislation, “the
Viral Hepatitis and Liver Cancer Control
Act,” was introduced in the US House of
Representatives by Congressmen Mike
Honda (D-Calif.) and Charles Dent (RPenn.)
and co-sponsored by 10 House
Members. HR 3974 would support a comprehensive
prevention, research, and
medical management referral program for
chronic hepatitis B and chronic hepatitis
C virus infection. The bill would provide
a relatively modest $90 million in funding
in 2011 – with additional funding
thereafter – that will increase the ability
of the Centers for Disease Control and
Prevention (CDC) to support state health
departments in their prevention, immunization
and surveillance efforts.
An estimated 5.4 million Americans
are infected with either chronic hepatitis
B or chronic hepatitis C infection. Most
individuals are not aware they are infected
and unable to take advantage of promising
treatments. According to the respected
research firm Milliman, the cost of chronic
hepatitis C virus infection alone could
reach $85 billion annually by 2024. Medicare
and Medicaid are projected to absorb
a disproportionate share of those
costs.
In January 2010, the Institute of Medicine
(IoM) is expected to release a report
on viral hepatitis in the United States that
outlines strategies for reducing the incidence
of viral hepatitis infection and to
mitigate complications in those individuals
with chronic infections.
Contact: Phil Blando,
202-258-4978
pblando@abmpartnersllc.com
Clinical Trial Opportunities
H___E___P__N___e__w___s___________________________________________________________________________p_a_g_e_ _3
www.medscape.com
Megan Brooks
November 2, 2009 (Boston, Ma)
After orthotopic liver transplantation
for hepatitis C virus (HCV), extending
antiviral therapy for 52 weeks after a first
HCV-negative result leads to low relapse
rates, according to research reported at
AASLD.
“In patients responding slowly to antiviral
therapy following orthotopic liver
transplant, the ‘stop rules’ at weeks 12
and 24 should be reconsidered,” lead
investigator Kimberly Brown, MD, head
of the Division of Gastroenterology at
the Henry Ford Hospital in Detroit,
Michigan, and colleagues report in their
meeting abstract.
In an interview with Medscape Gastroenterology
just prior to her presentation,
Dr. Brown said: “There are some
data in the pretransplant population that,
if you extend antiviral therapy, you reduce
relapse rates, especially in patients
who are responding slowly. The purpose
of our study was to extend therapy to
Extended HCV Treatment after Liver Transplant Has Benefits
see if we could do that in a posttransplant
population, and the results suggest that
we could.”
The study involved 241 consecutive
patients who underwent orthotopic liver
transplant from 1999 to 2006 for HCV.
Patients were offered therapy if they
tested positive for HCV RNA, had recurrent
HCV with at least stage 1 fibrosis,
and had stable immunosuppression
for at least 3 months.
Patients received either nonpegylated
interferon 3 times weekly or pegylated
interferon in combination with ribavirin
in standard doses. Treatment was continued
for 52 weeks after patients became
HCV-negative.
According to Dr. Brown, of the 241
patients, 66 were treated, 22 achieved
sustained virologic response, and only
2 (8%) relapsed. “A relapse rate of 8%
is quite a bit lower than the 30% that is
commonly cited in the literature,” she
told Medscape Gastroenterology.
She also noted that patients who
achieved sustained virologic response
were more likely to have had extended
treatment than those who did not (97.5
vs 59.9 weeks; P < .014).
Moreover, “35% of the patients who
went on to have a sustained virologic
response actually became virus-negative
after week 24,” Dr. Brown said. “This
suggests that even if patients are positive
at 24 weeks, there is still a 35%
chance that they can achieve sustained
viral clearance.”
Stuart C. Gordon, MD, also from the
Department of Gastroenterology and
Transplant Surgery at the Henry Ford
Hospital, but who was not involved in
the study, said: “These are very provocative
data that challenge a lot of long-held
paradigms. The standard of care has always
taught us that failure to achieve
viral negativity by 24 weeks is the end
of the line. This study shows that this is
not the case.”
“In light of these findings, our preconceived
notions about antiviral
therapy need to be re-explored,” he concluded.
www.reuters.com
November 3, 2009 - Boston, MA
All approved therapy regimens to
treat patients with hepatitis C are based
on interferon, which must be injected.
Interferon will still remain part of any
approved HCV treatment for at least several
years, but a new study points to the
possibility of interferon-free treatment
in the future. In this clinical trial presented
at AASLD, researchers treated
patients - both treatment naive and experienced
patients - with a twice daily
oral combination therapy of a nucleoside
polymerase and protease inhibitor.
The results were significant antiviral
potency and sustained viral reductions.
In addition, the therapy appeared safe
and well-tolerated. “The expected better
tolerability of these Interferon-free
combination DAA regimens may make
First Interferon-Free Treatment for Hepatitis C Shows Promise
treatment easier for patients and also allow
for patients to be treated who are
unable to take interferon based therapy,”
said Edward Gane, MD, lead investigator
on this study. “The greater numbers
treated and better success rates should
eventually help reduce the future projected
burden of end-stage liver disease
for chronic HCV.”
The INFORM-1 trial is randomized,
double-blind, and placebo controlled.
The oral therapy was administered over
a 14-day period, and the antiviral responses
were impressive among all
groups. It was reported that the combination
is undergoing further development
for treatment of chronic hepatitis
C. “This is the first study to demonstrate
that an IFN-free, twice daily, combination
DAA regimen produces similar antiviral
activity compared to triple therapy
(SOC plus protease) over 2 weeks of
treatment,” said Dr. Gane. “This combination
may represent the first IFN-free
treatment regimen for both treatmentnaive
and previously treated patients
with HCV Genotype 1 infection.”
These results are very promising in
regards of antiviral potency and lack of
resistance development. “From here we
will need to explore in a stepwise fashion
if longer treatment will result in persistent
viral suppression, clear all HCVinfected
hepatocytes and ultimately lead
to a sustained virologic response
(SVR),” said Dr. Gane. He concluded
by saying, “as we explore this new treatment
paradigm, we hope to gain a better
understanding of the virus host interaction
in HCV, as DAA induced viral suppression
in the absence of extrinsic interferon
allows us to study intrinsic interferon
responses and associated
biomarkers.”
_p_a_g_e _4____________________________________________________________________________________________ HEPNews
www.medicalnewstoday.com
Several studies have shown that lipid
peroxidation stimulates collagen production
in fibroblasts and hepatic stellate
cells (HSC), and plays an important role
in the development of liver fibrosis.
Hepatoprotective effects of green tea
against carbon tetrachloride, cholestasis
and alcohol induced liver fibrosis were
reported in many studies. However, the
hepatoprotective effect of green tea in
dimethylnitrosamine (DMN)-induced
models has not been studied.
A research article published on November
7, 2009 in the World Journal of
The Antifibrotic Effects of Green Tea
Gastroenterology addresses this. The
research team, led by Prof. Hong-Yon
Cho from Korea University examined
the protective effect of green tea extract
(GT) on hepatic fibrosis in a rat HSC
line and in a rat model of DMN-induced
hepatic fibrosis.
The results showed GT administration
prevented the development of hepatic
fibrosis in the rat model of DMNinduced
liver fibrosis. These results were
confirmed both by liver histology and
by quantitative measurement of hepatic
hydroxyproline content, a marker of liver
collagen deposition. Accordingly, inhibition
of proliferation, reduced collagen
deposition, and type 1 collagen expression
were observed in activated HSCT6
cells following GT treatment. These
results imply that GT reduced the proliferation
of activated HSC and down
regulated the collagen content and expression
of collagen type 1, thereby
ameliorating hepatic fibrosis.
The researchers drew a conclusion
that green tea may protect liver cells and
reduce the deposition of collagen fibers
in the liver. Green tea provides a safe
and effective strategy for improving hepatic
fibrosis.
www.medscape.com
Megan Brooks
November 5, 2009 (Boston, MA)
Supplementing pegylated interferonalfa2b
and ribavirin with a daily dose of
vitamin D might increase virologic response
rates, according to results of a
late-breaking abstract reported at Annual
Meeting of the American Association for
the Study of Liver Diseases (AASLD).
“Vitamin D is a potent immunomodulator
whose impact on virologic
response rates of interferon-based treatment
of chronic HCV [hepatitis C] is
unknown,” lead investigator Saif M.
Abu-Mouch, MD, from the Department
of Hepatology, Hillel Yaffe Medical
Center, in Hadera, Israel, and colleagues
note in their abstract.
“This preliminary study confirms the
benefit of adding vitamin D to conventional
antiviral therapy in patients with
chronic HCV,” Dr. Abu-Mouch told
Vitamin D May Have Benefits in Chronic HCV Infection
meeting attendees.
In the study, 58 patients with confirmed
chronic HCV (genotype 1) were
randomly assigned to peginterferonalfa2b
(1.5 μg/kg once weekly) plus
ribavirin (1000 to 2000 mg/day). Thirtyone
patients also received vitamin D
(1000 to 4000 IU/day; serum level >32
ng/mL).
The vitamin D group had a higher
mean body mass index (27 vs 24 kg/m2;
P < .01), viral load (68% vs 58%; P <
.01), and fibrosis (Metavir scores > F2,
55% vs 18%; P < .001) than the group
that did not receive vitamin D. Demographics,
disease characteristics,
ethnicity, baseline biochemical parameters,
and adherence to treatment were
similar in the 2 study groups.
A rapid virologic response was seen
at week 4 in 44% of the vitamin D group
and in 18% of the control group. At
week 12, Dr. Abu-Mouch told
Medscape Gastroenterology, 96% of the
vitamin D group (26 of 27 patients) were
HCV RNA-negative, as assessed by reverse-
transcriptase polymerase chain reaction,
as was 48% of the control group
(15 of 31 patients), which was a significant
difference (P < .001), he said.
The combination of peginterferon
and ribavirin, the current standard of
care for chronic HCV, achieves a sustained
virologic response in 40% to
50% of previously untreated patients
with genotype 1, the investigators explained.
Vitamin D in combination with
peginterferon-ribavirin “may have synergistic
effects,” Dr. Abu-Mouch said.
Laurent Tsakiris, MD, from the Centre
Hospitalier Universitaire de Melun
in France, said that “the study is surprising
and promising because vitamin D is
something very easy to use and there is
no toxicity.”
Potential Hepatitis C Breakthrough
A hepatitis C drug developed by Danish
company Santaris Pharma is creating
excitement in the medical community. In
preliminary testing done on chimpanzees
chronically infected with the hepatitis C
virus, SPC3649 dramatically reduced virus
levels with no toxic side effects. Drug
resistance, a common problem with currently
available hepatitis C treatments, was
not an issue. The results were reported in
this week’s online version of Science.
Unlike current therapies, SPC3649
does not target the virus directly. The hepatitis
C virus mutates continually, causing
patients to develop resistance to therapy.
Instead, SPC3649 inhibits a short RNA
(microRNA) molecule called miR-122
that is crucial for the replication of the
virus. In the animal study, four subjects
were given weekly 5 mg or 1 mg doses of
(Cont. on Pg.5)
HEPNews page 5
www.aidsmap.com
Gus Cairns
A course of hepatitis C (HCV) combination
therapy including the experimental
HCV protease inhibitor telaprevir (VX-
950) has produced a sustained viral response
(SVR) in over 80% of treatmentnaïve,
hepatitis C-mono-infected patients
with HCV genotype 1.
Another study found similar rates
achieved by another protease inhibitor,
boceprevir. The findings were annouced
on Tuesday at the American Association
for the Study of Liver Disease (AASLD)
meeting in Boston, USA.
This response rate is at least 30%
higher than the best SVR rates achieved
in trials of patients with genotype 1 monoinfection
treated with the standard
pegylated interferon/ribavirin regimen.
Eighty-two per cent of patients
achieved an SVR in 24 weeks (12 weeks
on telaprevir plus interferon/ribavirin and
12 on interferon/ribavirin alone), when
standard treatment for G1 lasts 48 weeks.
SVR, which is regarded as equivalent
to a cure, is defined as the lack of detectable
hepatitis C in the blood six months
after the cessation of therapy.
The results were superior to results
achieved in the previous PROVE studies
of telaprevir - see this report - where SVR
rates of nearly 70% were achieved compared
with under 50% in patients taking
telaprevir placebo.
Final results from the present study,
VX950-C208, were announced in a press
release from the two companies developing
the drug, Tibotec and Vertex, to accompany
the coference presentation. This
study had four differences from the
New Hepatitis C Protease Inhibitors Achieve 80% ‘Cure’ Rate
in Patients with Genotype 1 Infection
PROVE study:
* There was no placebo-controlled
arm: all patients took telaprevir;
* Half the patients took pegylated
interferon-alfa-2a (Pegasys) and half took
pegylated interferon-alfa-2b (PegIntron);
* Half the patients took 750mg of
telaprevir three times daily, as in the
PROVE studies, while half took 1250mg
twice daily;
* If patients achieved an undetectable
viral load by week four of the trial
and maintained it till week 20, they were
allowed to stop treatment at week 24. The
18% of patients who were exceptions to
this carried on treatment till week 48.
Eighty-five per cent of patients taking
telaprevir three times a day plus Pegasys
achieved an SVR, and 82.5% of those on
twice-a-day telaprevir.
In those taking PegIntron an SVR was
achieved in 81% of those on thrice-daily
telaprevir, and 82.1% twice-daily. These
differences were not statistically significant.
Interestingly, at week 12 there had
appeared to be a difference in results, with
93% with undetectable HCV on thricedaily
telaprevir and 84% on twice-daily.
Regarding side-effects, the press release
accompanying the trial results commented
that “adverse events were similar
to those observed in other trials with
telaprevir.” The only figures given were
for “serious adverse events leading to permanent
discontinuation of all drugs,”
which is a very restrictive definition. Three
per cent discontinued the study due to rash
by this criterion and 2% due to anaemia.
In the PROVE 1 and 2 trials 21% and 12%
of patients on telaprevir respectively discontinued
therapy versus 11% and 7% on
placebo. The main side effect of telaprevir
is rash, with was classed as ‘severe’ in 7%
and 15% of patients respectively in
PROVE 1 and 2.
Final figures for viral breakthrough
were not specified. Interim figures given
in the abstract showed that nine patients
(5.6%) had experienced an initial fall but
then rebound of HCV by week 12 and that
all nine had telaprevir resistance mutations.
The AASLD conference heard a lot of
other news about new hepatitis C drugs.
The results were also announced of
PROVE 3, a trial of telaprevir in patients
who have previously failed hepatitis C
therapy. In this trial, nearly 40% of patients
who previously failed to respond to
pegylated interferon/ribavirin and nearly
70% who had responded but relapsed
achieved an SVR with 24 weeks of treatment,
while 76% of relapsers had an SVR
with 48 weeks.
A study of Schering-Plough’s
boceprevir, the first hepatitis C protease
inhibitor to be trialled, found SVR rates
of 82% in patients with genotype 1 who
had an undetectable viral load by week
four, and 79% by those who had not
achieved one by week four but had by
week 16. And a second boceprevir study
found an SVR rate of 55% among patients
who had previously failed to respond to
pegylated interferon/ribavirin. In these
studies, pegylated interferon/ribavirin is
given for four weeks then boceprevir
added for 24 weeks (in naïve patients) and
44 weeks (in previous non-responders).
SPC3649 over a period of 12 weeks. Virus
levels dropped 350 percent in animals
that were given the larger dose. The drug
remained effective for up to several
months after treatment.
SPC3649 is the first microRNA-targeted
drug to be advanced to human clinical
trials. The Los Angeles Times reports
that microRNA has been shown to regulate
gene activity within cells. The hepatitis
C virus is the only virus known to use
miR-122 to replicate.
The World Health Organization estimates
that 170 million people worldwide
have chronic hepatitis C, which puts patients
at risk for liver diseases like cirrhosis
and liver cancer. Other companies developing
treatments for hepatitis C include
Monogram Biosciences, Sinovac Biotechnology,
Idenix Pharmaceuticals and
Novelos Therapeutics.
Breakthrough