Sustained
Response to Interferon-based Therapy for Hepatitis C Reduces Risk of Liver Toxicity
Due to Antiretroviral Drugs for HIV By
Liz Highleyman Some
antiretroviral drugs used to
treat HIV can cause hepatotoxicity (liver
toxicity), and the risk appears to be greater for individuals with pre-existing
liver disease including chronic viral hepatitis.
But
effective treatment of chronic hepatitis C virus
(HCV) infection reduces the likelihood of drug-related liver injury, according
to findings presented at the 44th Annual Meeting of the
European Association for the Study of the Liver (EASL 2009) last month in
Copenhagen. E.
Krastinova and colleagues from France sought to identify risk factors associated
with severe liver enzyme elevation in 248 HIV-HCV coinfected participants in the
ANRS HC EP10 RIBAVIC study who were taking combination antiretroviral therapy
after completing a full course interferon-based hepatitis C treatment. Three-quarters
of the patients were men and the average age was 41 years; 30% had advanced liver
fibrosis (Metavir score F3-F4).
Participants were followed for up to 6
years. Hepatotoxicity was defined as a more than 3.5-fold increase in alanine
aminotransferase (ALT) and/or aspartate aminotransferase (AST) from baseline levels
during follow-up. Liver fibrosis was assessed by biopsy performed at baseline
and after completion of a full 48-week course of treatment with conventional
or pegylated interferon plus ribavirin.
Results
Overall, 29% of patients achieved sustained virological response (SVR), or continued
undetectable HCV RNA at 24 weeks after completing treatment.
A total of 64 patients experienced episodes of liver toxicity during a mean 4.8
years of follow-up.
Hepatotoxicity occurred in almost all patients (98%) who did not achieve SVR,
compared with just 1 individual with SVR (P < 0.0001).
In Cox proportional hazards models with antiretroviral therapy as time-dependant
variable, the following were independent predictors of hepatotoxicity:
Lack of SVR: hazard ratio (HR) 31.8 (P < 0.001);
Use of didanosine (ddI; Videx)
and/or stavudine (d4T; Zerit):
HR 12.3 (P = 0.01).
Sustained
HCV clearance after [interferon/ribavirin]
based treatment reduced the risk of liver toxicity of antiretroviral therapy,"
the investigators concluded.
In patients without sustained response, they
added, "dideoxynucleosides [i.e., didanosine and stavudine] were associated
with a high risk of hepatotoxicity."
INSERM U707, Pierre and Marie
Curie University; INSERM U370, West Hospital Group University; East Hospital Group
University, University Paris, Paris, France; Archet Hospital, Nancy, France; Raymond
Poincare University Hospital, Versailles University, Garche, France.
5/29/09 Reference
E
Krastinova, F Bani-Sadr, S Pol, and others. Risk Factors for Hepatotoxicity of
ARV in HIV/HCV Co-infected Patients with a 6 Years Follow-Up after a Completion
of a Full Course Anti-HCV Treatment. 44th Annual Meeting of the European Association
for the Study of the Liver (EASL 2009). Copenhagen, Denmark. April 22-26, 2009.
EASL
2009 MAIN PAGE
15th
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