Risk factors of chronic hepatitis in antiretroviral-treated HIV infection, without hepatitis B or C viral infection

BACKGROUND Increasing rates of non-AIDS defining illnesses, and in particular liver diseases, have been found after the initiation of highly active antiretroviral therapy. However, there is little evidence concerning the risk factors for and clinical characteristics of liver disease in antiretroviral (ARV)-treated HIV infection, in the absence of hepatitis B or C viral co-infection. METHODS A nested case-control study of HIV infected volunteers, matched by starting date of anti-retroviral treatment, was conducted in a Thai cohort studied from Nov 2002 - July 2012. Cases were defined as those subjects with an elevated alanine aminotransferase (ALT ≥ 40 IU/L) at two consecutive visits six months apart, while controls were defined as individuals who never demonstrated two consecutive elevated ALT results and had a normal ALT result (< 40 IU/L) at their last visit. Both groups had normal ALT levels prior to ARV initiation. Clinical demographics and risk factors for chronic hepatitis including HIV-related illness, ARV treatment and metabolic diseases were collected and analyzed. Conditional logistic regression was used to determine risk factors for chronic hepatitis in HIV infection. RESULTS A total of 124 matched pairs with HIV infection were followed over 3,195 person-years. The mean age (±SD) was 33.0 ± 7.3 years, with 41.1% of subjects being male. The incidence of chronic hepatitis was 5.4 per 100 person-years. The median time from initiation of ARV to chronic hepatitis was 1.3 years (IQR, 0.5-3.5). From univariate analysis; male sex, plasma HIV-1 RNA level > 5 log 10 copies/ml, metabolic syndrome at baseline visit, high BMI > 23 kg/m(2), abnormal HDL cholesterol at time of ALT elevation and treatment experience with NNRTI plus boosted PI were selected (p value < 0.2) to the final model of multivariate analysis. Male sex had 3.1 times greater risk of chronic hepatitis than the females by multivariate analysis (adjusted OR, 95% CI: 3.1, 1.5-6.3, p =0.002). High BMI ≥ 23 kg/m(2) was also associated with 2.4 times greater risk of chronic hepatitis (adjusted OR, 95% CI: 2.4, 1.2-4.8, p = 0.01). CONCLUSIONS Chronic hepatitis in ARV-treated HIV-infected patients is common and may lead to a major health care problem. Male sex and high BMI ≥ 23 kg/m(2) carry higher risks for developing chronic hepatitis in this study. Therefore, these patients should be closely monitored for long-term hepatotoxicity.