Several prior studies have shown that the risk of
hepatotoxicity due to antiretroviral drugs is higher in people with pre-existing
liver disease, including chronic hepatitis B or C.
This suggests that
the chances of hepatotoxicity might fall if liver injury is halted after sustained
response to hepatitis C treatment -- a hypothesis recently tested by researchers
from Hospital Carlos III in Madrid, Spain.
In the present study, the incidence
of severe elevations in liver enzyme (ALT and AST) levels during use of antiretroviral
therapy was retrospectively analyzed in 132 HIV-HCV coinfected patients who completed
a full course of interferon-based treatment for hepatitis C. Most (66%) were men
and the mean age was 38 years.
Hepatic events were recorded according to
whether or not the patients achieved sustained virological response (SVR), or
continued undetectable HCV RNA 24 weeks after the completion of treatment. The
presence of advanced liver fibrosis was estimated using transient elastometry
(FibroScan). Results
•
Overall, 33% of patients
achieved SVR.
•
40% had advanced liver
fibrosis after interferon-based therapy.
•
A total of 49 episodes
of liver toxicity occurred during a mean 35 months of follow-up (9.7% per year)
after interferon-based therapy.
•
The yearly incidence
of hepatic events was greater in patients who did not achieve SVR compared with
those who did (12.9% vs 3.1%; P < 0.001).
•
Likewise, hepatic events
were more common among patients with advanced liver fibrosis than those with milder
or absent fibrosis (14.4% vs 7.6%; P = 0.003).
•
Antiretroviral drugs
most often associated with hepatic events were:
- dideoxynucleoside analogues,
i.e., ddI (didanosine, Videx) and d4T (stavudine, Zerit): 40%; - the NNRTI
nevirapine (Viramune): 30%; - the NNRTI efavirenz (Sustiva): 11%; - protease
inhibitors: 8%.
•
In a logistic regression
analysis, failure to achieve SVR (OR 6.13; P = 0.003) and use of ddI or d4T (OR
3.59; P = 0.02) were independent predictors of hepatotoxicity after completing
interferon-based therapy.
•
Conversely, regimens
containing a protease inhibitor (OR 0.07; P < 0.01) or efavirenz (OR 13; P
= 0.001) were associated with a reduced risk of drug-related hepatic events.
Conclusion
"Sustained
HCV clearance after interferon-based therapy reduces the risk of liver toxicity
during antiretroviral therapy, which should further encourage the treatment of
chronic hepatitis C in HIV-coinfected patients," the authors concluded.
"In
this population, prescription of protease inhibitors or efavirenz decreases and
use of dideoxynucleoside analogues increases the risk of hepatotoxicity,"
they added.
These findings suggest that it may be preferable to treat hepatitis
C before starting antiretroviral therapy if a person has a high enough CD4 cell
count and no symptoms of HIV disease. This approach is plausible because hepatitis
C treatment lasts 6 to 12 months (depending on HCV genotype), and studies suggest
that CD4 counts are unlikely to fall dramatically during this amount of time if
an individual starts with a high level. Nevertheless, delaying HAART does increase
the risk of HIV disease progression, so patients should receive regular medical
monitoring.
09/28/07
Reference P
Labarga, V Soriano, ME Vispo, and others. Hepatotoxicity of antiretroviral drugs
is reduced after successful treatment of chronic hepatitis C in HIV-infected patients.
Journal of Infectious Diseases 196(5): 670-676. September 1, 2007.
