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July 26, 2006
Risk Factors Identified in HIV-HCV Steatosis (Reuters Health)
July 26, 2006 (Reuters Health)—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 stenosis 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."
