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Friday 26th May, 2006
Studies demonstrate improved virus
suppression, identify response factors in treating
LOS ANGELES (May 21, 2006) - According to recent estimates,
hepatitis has become a worldwide health problem, affecting
millions of people in the U.S. and abroad.
Researchers are experimenting with combinations of
anti-inflammatory medicines like interferons to improve
hepatitis symptoms. In research presented today at Digestive
Disease Week? 2006 (DDW), new combinations of therapies are
making significant progress to improve symptoms of the disease.
DDW is the largest international gathering of physicians and
researchers in the fields of gastroenterology, hepatology,
endoscopy and gastrointestinal surgery.
Hepatitis is caused by a virus that attacks the liver,
triggering painful inflammation and often leading to more
serious conditions like liver failure and even death. Several
different forms of hepatitis exist, including hepatitis A, B and
C. Hepatitis A is generally food-borne, while hepatitis B and C
are spread primarily through parenteral or sexual routes. The
disease is often caused by a virus, but can also result from
alcohol, toxins or drugs.
"Despite the significant number of people suffering from
hepatitis, treatment options have been lagging in comparison to
other major diseases," said John Vierling, M.D., FACP,
president, the American Association for the Study of Liver
Diseases (AASLD); professor of Medicine and Surgery at the
Baylor College of Medicine in Houston, Texas; and director of
Baylor Liver Health and Chief of Hepatology. "We hope that
continued research like these studies will lead to more
significant breakthroughs and relief for these patients."
Valopicitabine (NM283), Alone or with Peg-Interferon,
Compared to Peg Interferon/Ribavirin (pegIFN/RBV) Retreatment in
Hepatitis C Patients with Prior Non-Response to PegIFN/RBV: Week
24 Results [Abstract 4]
More than half of currently treated hepatitis patients are
infected with strains of hepatitis C that do not respond to
current interferon therapies and have no other effective
treatment options. Combination treatment using a new antiviral
therapy is showing promise in suppressing the virus, according
to a phase II US multi-center study. The therapy, valopicitabine,
has shown anti-HCV activity alone and in combination with pegIFN
(pegylated interferon) in early trials, without viral
breakthrough for study periods up to six months.
The current study compared the outcomes of five different
treatments in patients who have not experienced remission with
standard therapies: valopicitabine alone (800 mg/d), one of
three combination arms with the drug at 400 mg/d, 800 mg/d or
dose-ramping 400 to 800 mg/d plus pegIFN, or pegIFN with
ribavirin as a control group.
For the 162 patients who have completed the trial period at
24 weeks, results show that the two higher-dose combination arms
had much better response rates than the control group,
experiencing on average a 2.5 to 3.0 log decrease in hepatitis
RNA reductions by week 24, a significantly better response than
the comparator. No viral breakthrough has been seen to date.
However, vomiting and dehydration requiring hospitalization
occurred in three patients taking the highest dose (800 mg),
forcing the research team to halt the use of that dose and
continue using only the lower doses of 200 to 400 mg of the
"For patients whose disease has not responded to current
therapies, this new combination treatment may produce excellent
results, at the maximally acceptable dosage," according to Paul
Pockros, M.D., of Scripps Clinic in California, and lead study
author. "Continued treatment will determine if these encouraging
early responses will result in a sustained response, hopefully
improving patient quality of life and long-term survival."
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Comparison of Daily Consensus Interferon versus Peginterferon
alfa 2a Extended Therapy of 72 Weeks for Peginterferon /
Ribavirin Relapse Patients with Chronic Hepatitis C [Abstract
In chronic diseases like hepatitis, symptoms have a tendency
to fluctuate in severity. As a result, researchers are finding
that the diseases may react more successfully to a longer
duration of therapy. In this study, researchers at the
University of Tuebingen in Germany compared two combination
therapies for an extended treatment period of 72 weeks, compared
to the current standard of 48 weeks, in patients with chronic
Previous studies have shown that with 48 weeks of therapy,
relapse rates are near 20 to 30 percent, but with an extended
duration of 72 weeks, rates may be reduced. The research team
compared the efficacy of daily doses of CIFN (consensus
interferon) plus ribavirin (RBV) versus pegIFN (pegylated
interferon alfa 2a) plus RBV for 72 weeks in patients with a
prior relapse to 48 weeks of treatment. A total of 81 patients
were treated with either CIFN or with pegIFN a2a for 72 weeks,
both in combination with RBV.
After the initial 12 weeks, a primary response to therapy,
noted as a reduction in hepatitis RNA, was observed in 83
percent of patients in the CIFN group and 78 percent of the
pegIFN group. At the end of treatment at week 72, the vast
majority (89 percent) of both the CIFN group and pegIFN group
(76 percent) were in remission. After finishing treatment,
two-thirds of the CIFN group (69 percent) experienced sustained
response, but less than half of the pegIFN group (44 percent)
experienced these results, indicating a significantly higher
relapse rate in this group.
"While many patients did relapse after discontinuing
treatment, the overall sustained response rates are nevertheless
promising, showing a sustained response in up to 70 percent of
patients," said Stephan Kaiser, M.D., of the University of
Tuebingen, and lead study author. "We believe that extended
treatment with CIFN combined with RBV may be a better option
than current standards for this difficult-to-treat patient
The overall tolerability of the CIFN regimen was comparable
to PEG IFN. Three patients experienced thrombocytopenias
(reduced blood platelets), but there were no severe neutropenias
(low white blood cell count) or thrombocytopenias. CIFN patients
experienced a higher rate of injection site reactions and a
slightly higher drop-out rate of 18 percent, compared to only 12
percent of the pegIFN group.
28 Days of the Hepatitis C Protease Inhibitor VX-950, In
Combination with Peg-Interferon-Alfa-2a and Ribavirin, is
Well-Tolerated and Demonstrates Robust Antiviral Effects
Scientists are reviewing new compounds in combination with
current standard hepatitis therapies to produce better patient
outcomes. A new oral peptidomimetic protease inhibitor, VX-950,
has previously shown substantial anti-viral effects in
combination with the frequently used hepatitis therapy pegylated
interferon (pegIFN). In this study, researchers evaluated the
safety and antiviral response of VX-950 in combination with
pegIFN and ribavirin (RBV).
The study included 12 hepatitis C patients who received 750
mg of VX-950 every eight hours, 180 ? of pegIFN weekly, and
either 1000 or 1200 mg of RBV daily. After 28 days, patients
began standard therapy with pegIFN/RBV.
All patients responded to the study drug regimen and showed
continual declines in hepatitis RNA throughout the treatment
period. Two patients had levels of HCV RNA in their blood below
the limits of detection of a highly sensitive assay after just
eight days. All patients had undetectable HCV RNA by the end of
28 days. No patients experienced viral breakthrough at any time.
"These data confirm the rapid and dramatic antiviral effects
of VX-950. All subjects achieving undetectable HCV RNA within 28
days of treatment is an unprecedented result with an
investigational agent," said Eric Lawitz, M.D., of Alamo Medical
Research, Texas, and lead author of the study. "We look forward
to future studies which will evaluate the ability of VX-950 to
produce sustained viral responses with as little as 12 weeks of
therapy." VX-950 + pegIFN + RBV was well tolerated, with no
serious adverse events and no treatment discontinuations. A
detailed analysis of adverse events will be presented.
Acetaminophen as a co-factor in acute liver failure due to
viral hepatitis determined by measurement of
acetaminophen-protein adducts [Abstract S1002]
Acetaminophen (APAP) is a common over-the-counter medication
present in more than 300 preparations for pain relief and
flu-like symptoms. But for people who are suffering from viral
hepatitis A or B, use of acetaminophen may play a role in
accelerating liver failure, ordinarily a rare complication of
Serum samples from 72 patients with proven hepatitis A or B
that had progressed to liver failure were tested for APAP
adducts, which are the toxic byproducts of acetaminophen liver
damage, created when a chemical (in this case, acetaminophen)
binds to proteins in the liver that are then released into the
blood when cells die. As a positive control group, the team also
included 10 documented cases of acute liver failure (ALF)
resulting directly from large APAP overdoses.
Results from the examination showed that nine of the 72
patients (12.5 percent) had detectable APAP adducts in their
blood, signifying that some of their liver damage was APAP-related.
All 10 known APAP-induced ALF cases had positive adducts at much
higher levels than those in the viral hepatitis group (average
level of 5.58 nmol/mL versus 0.45 nmol/mL, respectively).
Two-thirds (67 percent) of the hepatitis patients with APAP
adducts died within three weeks of study admission, compared to
only 27 percent of hepatitis patients without adducts.
Most of the patients with adducts reported some APAP use in
the days prior to the study, but none reported doses exceeding
four grams per day. Flu-like symptoms, nausea and vomiting are
common in patients with early viral hepatitis and APAP is
commonly used in this setting.
"This study suggests that acetaminophen, even when taken at
therapeutic dosages, is responsible for a second hit in viral
hepatitis and explains why some patients develop acute liver
failure and death in this setting," said William M. Lee, M.D.,
of the UT Southwestern Medical Center in Texas, and senior study
author. "Warnings regarding use of acetaminophen should be
clearly communicated to patients with acute viral hepatitis,
particularly those of moderate severity, to reduce these bad
outcomes from a relatively benign disease."