AASLD 2009 HBV News Updates November 6, 2009
● Gilead Finds Viread Sustains Suppression of Hepatitis B
Hepatitis B Immune Globulin Therapy May
Improve Graft and Patient Survival after Liver Transplantation
By Cheryl Lathrop
HBIG did not statistically significantly improve graft or
patient survival relative to all other patients, but there was a trend towards
a reduction in risk, noted Michael R. Marvin, MD,
At the 2009 American Transplant Congress last spring, Dr.
Marvin and colleagues presented results of a multivariate study demonstrating
that patients treated with HBIG for prophylaxis of de novo hepatitis had
increased patient and graft survival when HBIG was used,
compared with lamivudine.
To follow up this result, they screened the United Network
for Organ Sharing (UNOS) Standard Transplant Analysis and Research (
Differences in patient/graft survival between groups were
adjusted for significant covariates using multivariable Cox models.
In the coinfected cohort, 797 transplant patients were
examined. In all, 101 of these patients received HBIG alone, 15 patients
received lamivudine alone, 19 received both treatments, 304 received neither
treatment, and 358 had missing information. Among the 22,341 patients known to
be HBSAg(-) but HepC(+), 236 received HBIG alone, 124
received lamivudine alone, 67 received both, 12,559 received neither, and the
rest had missing information.
HBIG did not statistically significantly improve graft or
patient survival relative to all other patients, but there was a trend towards
a reduction in risk (graft, P = .26; patient, P = .065). Graft failure for the
lamivudine-only patients relative to the "neither therapy" group was
the worst (hazard ratio = 1.5; 95% confidence interval, 1.08-2.07; P = .015).
HBIG conferred an approximately 40% reduction in the risk of graft failure (P =
.01) and patient death (P = .018) relative to lamivudine-only treatment.
In the cohort comprising the entire UNOS database, 90,867
transplant recipients were examined. In all, 1,604 received HBIG alone, 265
received lamivudine alone, 280 received both treatments, 36,986 received
neither treatment, and 51,732 had missing information. There were significant
differences in adjusted patient and graft survival with the HBIG-only group, which
exhibited improved graft and patient survival over the lamivudine-only group (P
= .003 and P = .0003, respectively). Survival of the combination-therapy group
was in the middle, between the lamivudine and the HBIG-only groups.
The UNOS registry data suggest that HBIG therapy is
associated with improved graft/patient survival versus lamivudine,
independently of de novo hepatitis B reduction in liver transplant recipients.
"The mechanism by which HBIG offers this survival
advantage is not clear, and warrants further study," the authors noted.
[Presentation title:
HBIG May Improve Graft and Patient Survival After
Liver Transplantation. Abstract 521]
Gilead Finds
Viread Sustains Suppression of Hepatitis B
By Alaric DeArment
BOSTON (Nov. 2) Most patients who took an investigational drug for hepatitis B infection kept the number of copies of the virus in their bloodstream low, and some may be curable, according to results of two late-stage trials of the drug released Saturday.
Gilead Sciences announced results of phase 3 studies conducted over three years of the drug Viread (tenofovir disoproxil fumarate), which the company will present at the annual meeting of the American Association for the Study of Liver Diseases in Boston, which began Friday and continues until Tuesday.
The studies found that most patients with chronic hepatitis B receiving the drug lowered their viral load to 400 copies per milliliter of blood and kept it at that level, and 8% of patients experienced loss of the “s” antigen, which can contribute to curing of the disease. No patients experienced mutations of the virus that would allow it to become immune to the drug.
“The development of resistance is a significant challenge for practitioners treating patients with chronic hepatitis B,” physician and principal investigator of one of the trials Patrick Marcellin of Hopital Beaujon in Clichy, France, said in a statement. “The robust and comprehensive resistance surveillance in these studies provides important information for the medical community and shows that Viread offers a high barrier to resistance.”
BARACLUDE® (entecavir) Demonstrated Greater Antiviral Efficacy Compared to Adefovir in New Study of Chronic Hepatitis B Patients with Evidence of Decompensated Cirrhosis
Bristol-Myers Squibb (NYSE:
Decompensated cirrhosis is characterized by severe scarring of the liver caused by chronic liver inflammation, including inflammation associated with chronic hepatitis B infection. It is estimated that 15 to 25 percent of chronic hepatitis B patients die from complications of liver disease.1 Currently, the median survival rate in decompensated patients is two to three years, with only 28 percent of patients surviving for more than five years.2,3 The treatment of chronic hepatitis B patients with decompensated cirrhosis remains an area of unmet medical need, and these patients often require liver transplant.
"This study represents an
important first step in addressing an unmet medical need, as this is one of the
first comparative studies to evaluate the safety and efficacy of antiviral
therapy in this difficult-to-treat patient population,” said Professor Hugo
Cheinquer,
Study Results through Week 48
The primary study endpoint of
A statistically significant
difference was observed in the proportion of patients achieving undetectable
viral load [HBV
Additionally, of the 100 patients treated with BARACLUDE, 66 percent had an improvement or no worsening of the Child-Pugh Score (which assesses severity of hepatic decompensation), with 32 percent of patients having achieved a = 2-point reduction in Child-Pugh score at Week 24; these rates were 61 percent and 35 percent, respectively, at Week 48. Findings at Weeks 24 and 48 were comparable for patients receiving adefovir; 71 percent saw an improvement or no worsening of the Child-Pugh Score and 24 percent achieved a = 2-point reduction in Child-Pugh score at Week 24; these rates were 67 percent and 27 percent, respectively, at Week 48. Patients treated with BARACLUDE also experienced an improvement of the Model for End-Stage Liver Disease (MELD) Score (another scoring system that assesses severity of hepatic decompensation). The change from baseline for patients treated with BARACLUDE was a decrease of 2.6 points compared with 1.7 points for patients treated with adefovir at Week 48.
The overall safety profile was
comparable across the two treatments. As might be expected in this patient
population, the overall incidence of adverse events was high with 89 percent
(91/102) for the BARACLUDE arm and 97 percent (86/89) for the adefovir arm.
Serious adverse events occurred in 69 percent (70/102) and 66 percent (59/89)
of BARACLUDE- and adefovir-treated patients, respectively. Rates for death and
hepatocellular carcinoma (
About
Study
Study
Patients were randomized to receive BARACLUDE 1 mg or adefovir 10 mg daily and were treated for a minimum of 96 weeks. Baseline patient populations were comparable in the two treatment arms. Patients had a mean MELD score of 17 and 15, respectively, in the BARACLUDE and adefovir treatment groups. Approximately one third of patients were previously exposed and resistant to lamivudine.
The primary study endpoint was the
mean change from baseline HBV
Secondary study endpoints specific to measuring improvement in cirrhosis included the MELD Score, an exam which scores patients on the severity of chronic liver disease, and the Child-Pugh Score (greater than or equal to a two-point decrease), which were evaluated at baseline, Week 24 and Week 48.