Antiretroviral therapy-induced liver alterations.
OBJECTIVE
Antiretroviral drugs are associated with hepatotoxicity. Progress in our knowledge on the prevalence, contributory factors and mechanisms is reviewed.


RESULTS
Liver toxicity is highly prevalent and a major cause of hospitalization among HIV-infected individuals. Liver steatosis is probably more frequent in the setting of hepatitis C virus coinfection but is also seen in noncoinfected patients. Among the individual drugs, severe liver toxicity is more strongly associated with nevirapine, and the mitochondrial toxicity of some nucleoside analogues. Mitochondrial toxicity can also induce or contribute to steatohepatitis, with dietary uridine supplementation as a possible strategy of prevention. Atazanavir inhibits UDP-glucuronosyltransferase, which in Gilberts' syndrome has been associated with breast cancer. A UDP-glucuronosyltransferase gene promoter variant predisposes to hyperbilirubinemia. Tipranavir induces elevated transaminases more frequently than boosted comparator protease inhibitors. CCR5 inhibitors may predispose to hepatotoxic events by causing an imbalance in the cytokine response.


CONCLUSIONS
Hepatotoxicity is associated with all classes of antiretroviral agents and continues to contribute to hospitalization.
Walker
Ulrich A
UA
Department of Rheumatology and Clinical Immunology, Freiburg University Hospital, D-79106 Freiburg, Germany. ulrich.walker@klinikum.uni-freiburg.de