Steatosis Prevalent in HIV-HCV Coinfection; Risk Factors Identified

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By Megan Rauscher
NEW YORK (Reuters Health) Jul 26 - In patients co-infected with HIV and
hepatitis C virus (HCV), hepatic steatosis is prevalent and associated with
nucleoside analogue use, HCV genotype 3 infection and fibrosis, clinicians from
Massachusetts and Rhode Island report.
Dr. Barbara H. McGovern from Lemuel Shattuck Hospital in Jamaica Plain,
Massachusetts and colleagues reviewed the charts of 183 HIV-HCV-coinfected
patients and found that liver steatosis affected 69% (31% with minimal
steatosis; 27% with mild steatosis; 18% with moderate steatosis; and 1% with
severe steatosis.)
The use of the "D drugs," such as d4T (stavudine) and ddI (didanosine), was
strongly associated with the presence of steatosis (odds ratio, 4.63), the team
reports. This clinical observation is supported by in vitro and in vivo data
that suggest that didanosine and stavudine have significant mitochondrial
toxicity that exceeds that of other drugs," note Dr. McGovern and colleagues in
the August 1st issue of Clinical Infectious Diseases.
"This finding makes biological sense," Dr. McGovern told Reuters Health,
"since we know that these agents have great affinity for mitochondrial DNA
polymerase gamma. Through this pathway, these medications can cause
mitochondrial toxicity, which can manifest as microvesicular steatosis."
In addition, the investigators found that in patients with steatosis the odds
ratio of fibrosis was 1.37.
The use of antiretroviral agents with little or no mitochondrial toxicity
(e.g., tenofovir, lamivudine, emtricitabine, or abacavir) may be preferable to
other nucleoside reverse transcriptase inhibitors (NRTI) whenever possible, the
clinicians suggest.
In patients with HCV alone, HCV genotype 3 infection was also associated with
steatosis, with an odds ratio of 3.38. "This implies that patients with HIV/HCV
should be considered for therapy of hepatitis C, particularly if they have
genotype 3 since this infection responds well to treatment," Dr. McGovern said.
In a related editorial, Drs. Marija Zeremski and Andrew H. Talal, from Weill
Medical College of Cornell University in New York contend that "suspicion of
hepatic steatosis should be an additional indication for obtaining a liver
biopsy specimen from HIV/HCV-coinfected patients who are initiating an
antiretroviral therapy regimen that contains an NRTI."
The current study, they add, has "strengthened the connection between NRTI use
and steatosis. The physicians agree that in the clinical treatment of
HIV/HCV-coinfected patients, and especially for those with steatosis, the
"D-drugs" should be used cautiously."
Clin Infect Dis 2006;43:365-376.


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