Background:  The presence of co-infection by hepatitis C virus (HCV) is a known risk factor for hepatotoxicity in HIV-infected patients receiving HAART. The aim of this study was to asses the influence of liver histologic stage in the rate of HAART-related liver toxicity.

Methods:  This prospective cohort study consists of 107 HIV/HCV co-infected patients who underwent liver biopsy between October 2000 and September 2003. Liver fibrosis was staged using a scoring system of 0 (no fibrosis) to 4 (cirrhosis). Hepatotoxicity was defined as at least 5-fold increase from AST/ALT upper limit (or 3- to 5-fold increase from baseline AST/ALT levels when those are not normal), with no known other precipitating cause, and occurring after the date of biopsy or for a period of 3 years before. Patients with clinical symptoms of liver toxicity were also included.

Results:  Mean age was 39 years; 86% of patients were IDU as risk practice for HIV/HCV co-infection. Most patients had a fibrosis stage 1 (38%) or 3 (34%). Median time of known HCV infection was 17.6 years (3 to 25.6). Overall, there were 27 episodes of hepatotoxicity (25%; 5.1 cases/100 person-years on therapy), predominantly in patients with advanced chronic liver disease (38% in patients with fibrosis 3-4 vs 15% with fibrosis 1-2; RR 3.32; 95%CI:  1.3 to 8.3; p = 0.013). HCV infection time, accumulated time on HAART, AIDS diagnosis, HCV viral load, HCV genotype, and CD4⁺ nadir levels were not associated with hepatotoxicity. Only 10 patients (37%) changed or stopped temporally antiretroviral therapy. Specifically, during the study period, 86 patients (80%) received nevirapine (40 cases, 75.2 person-years) or efavirenz (46, 95.5 person-years), and 12 (16%) had liver toxicity while receiving nevirapine (7) or efavirenz (5). The presence of fibrosis stage 1-2 was associated with a lower rate of toxicity in all cases (5%, 3/100 person-years for nevirapine; 7%, 3.3/100 person-years for efavirenz; 3.4/100 person-years in patients not receiving NNRTI). However, there was a greater incidence of hepatotoxicity in patients with fibrosis 3-4 receiving NNRTI (25%, 11.7/100 person-years for nevirapine; 18%. 8.6/100 person-years for efavirenz; 4/100 person-years for the remaining patients). These results remained unchanged after adjusting by CD4+ count, HIV RNA level, time on HCV infection or other therapies.

Conclusions:  In HIV/HCV co-infected patients, the rate of HAART-associated hepatotoxicity is correlated with liver histologic stage. Specifically, there was no difference in the rate of hepatotoxicity for patients with mild or moderate fibrosis receiving NNRTI.  

Keywords: hepatotoxicity; HCV; NNRTIs