Liver toxicity in epidemiological cohorts

Hepatotoxicity has been demonstrated to be associated with antiretroviral therapy. Previous studies have included small numbers of patients and, thus, were unable to produce adequate statistical comparisons. I review data analyses from the Amsterdam, CHORUS, ICONA and Target studies (5133 patients), which were conducted by a number of investigators. There were differences between the cohorts with respect to the incidence of viral hepatitis and definitions of hepatotoxicity used. However, in all cohorts, hepatotoxicity in human immunodeficiency virus type 1-infected patients was significantly associated with coinfection with viral hepatitis. In 3 cohorts, elevated baseline alanine aminotransferase levels predicted subsequent hepatotoxicity. Overall, there was a low incidence of long-term hepatotoxicity in these cohorts and no consistent association between a particular drug or drug class. Nevirapine use within the first 12 weeks after initiation of therapy with this drug and ritonavir use are associated with increased risk of antiretroviral-associated hepatotoxicity.