Rate and risk factors of liver toxicity in patients receiving antiretroviral therapy

BACKGROUND: The benefit of highly active antiretroviral therapy (HAART) may be limited by the development of liver toxicity. The prevalence and risk f actors of this complication using different antiretroviral drug combination s are not well known. PATIENTS AND METHOD; Clinical charts of HIV-infected patients, previously n aive for antiretroviral drugs, starting HAART between January 1997 and Janu ary 2000 were reviewed. Liver toxicity was scored according to increases in liver enzymes. RESULTS: HIV infection had been acquired by intravenous drug use in 36 (40% ) of 91 subjects recruited in the study. The rest had been infected through homosexual (38%) or heterosexual contact (22%). Overall, 43 patients (47%) were coinfected with hepatitis C (42%) and/or B (8%) viruses. Antiretrovir al therapy included protease inhibitors (PI) plus two nucleosides in 48 ind ividuals and non-nucleosides in 50. Baseline characteristics were similar a cross the different treatment groups. Liver toxicity was recorded in 30 (31 %) subjects, and it was severe in 10 (11%). Cytolysis was the predominant p attern (28), while only one case of cholestasis and one with a mixed patter n were recorded. Coinfection with hepatitis B and/or C viruses was associat ed with liver toxicity (RR: 10.36; 95% Cl, 1.38-77.56; p = 0.03) as was a h igh alcohol intake (RR: 3.35; 95% Cl, 2.43-4.62; p = 0.01). No differences in the rate of hepatotoxicity were found when comparing PI and non-nucleosi de containing regimens. The development of isolated hyperbilirubinemia (27% ) was strongly associated with the use of indinavir (RR: 3.61; 95% Cl, 1.81 -7.21; p < 0.001). CONCLUSIONS: Liver toxicity occurs in about one third of HIV-infected patie nts after initiating HAART, regardless of the drugs used, yet it is commonl y mild and transient. A high alcohol intake and a coinfection with HCV/HBV constitute the most important predictive factors.