By Liz Highleyman

Use of antiretroviral therapy has been linked to liver toxicity in numerous studies.

One type of toxicity, indicated by elevated liver enzymes such as ALT and AST, is associated with several classes of drugs used to treat many diseases, including protease inhibitors for HIV. Nevirapine (Viramune) can cause a hypersensitivity reaction involving the liver, especially in people with high CD4 cell counts.

Another type of hepatotoxicity characterized by liver steatosis (fat accumulation) and hepatomegaly (enlargement) has been seen in patients taking certain nucleoside reverse transcriptase inhibitors, in particular the "d-dugs" stavudine (d4T; Zerit) and didanosine (ddI; Videx) - especially when used in combination. This has been attributed to mitochondrial toxicity, or damage to energy-producing structures within cells.

Several studies have shown that individuals with pre-existing liver disease, including chronic hepatitis C, are more susceptible to hepatotoxicity. But research has not produced consistent results, with some studies showing specific drugs to be associated with liver injury and others failing to replicate the findings.

To shed further light on this issue, Motoi Matsukura and colleagues performed a detailed study of mitochondrial damage in liver biopsy samples from HIV-HCV coinfected individuals. Results were reported in the June 19, 2008 issue of AIDS.

The analysis included 14 coinfected patients taking combination HAART and 9 who were not on HAART. Liver biopsy samples were assessed by electron microscopy quantitative morphometric analyses.

Results

In conclusion, the study authors wrote, "We found no evidence of increased mitochondrial toxicity in individuals currently on HAART, suggesting that concomitant HAART should not delay HCV therapy."

The incidence of steatosis/hepatomegaly liver toxicity has decreased since the "d-drugs" have fallen out of favor due to their side effects, at least in industrialized countries. U.S. and European HIV treatment guidelines no longer recommend these drugs for first-line therapy, but they are still commonly used in resource-limited settings due to their low cost and wide availability.

6/13/08

Reference
M Matsukura, F Chu, M Au, and others. Liver ultrastructural morphology and mitochondrial DNA levels in HIV/hepatitis C virus coinfection: no evidence of mitochondrial damage with highly active antiretroviral therapy. AIDS 22(10): 1226-1229. June 19, 2008.