Liver Enzymes Elevation and Immune Reconstitution Among Treatment-Naïve HIV-Infected Patients Instituting Antiretroviral Therapy

• Published in: The American journal of the medical sciences 2007-11, Vol.334 (5), p.334-341
• Main Authors: Ofotokun, Ighovwerha, Lennox, Jeffrey L., Smithson, Sarah E., Lu, Chengxing, Easley, Kirk A.
• Format: Article
• Language: English
• Subjects: Adult; Alanine Transaminase - blood; Alkynes; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Anti-Retroviral Agents - adverse effects; Anti-Retroviral Agents - therapeutic use; Antiretroviral drugs; Aspartate Aminotransferases - blood; Benzoxazines - adverse effects; Biological and medical sciences; CD4-Positive T-Lymphocytes - pathology; Cyclopropanes; Drug Therapy, Combination; Female; General aspects; Hepatitis B - blood; Hepatitis B - complications; Hepatitis B - pathology; Hepatitis B virus; Hepatitis C - blood; Hepatitis C - complications; Hepatitis C - pathology; Hepatitis C virus; Hepatotoxicity; HIV Infections - blood; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - enzymology; HIV/AIDS; Human immunodeficiency virus; Human viral diseases; Humans; Immune reconstitution; Immune Reconstitution Inflammatory Syndrome - blood; Immune Reconstitution Inflammatory Syndrome - chemically induced; Immune Reconstitution Inflammatory Syndrome - pathology; Infectious diseases; Lamivudine - adverse effects; Lamivudine - therapeutic use; Linear Models; Liver enzymes elevation; Male; Medical sciences; Middle Aged; Multivariate Analysis; Retrospective Studies; Risk Factors; Stavudine - adverse effects; Stavudine - therapeutic use; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Zidovudine - adverse effects; Zidovudine - therapeutic use
• ISSN: 0002-9629; 1538-2990
• DOI: 10.1097/MAJ.0b013e31811ec780

Because liver enzymes elevation (LEE) complicates antiretroviral (ARV) therapy, and because the strongest risk factor for ARV-related LEE is HBV/HCV coinfection, it is speculated that ARV-related LEE may be a form of immune reconstitution disease. This study summarizes the relation between immune reconstitution, ARV-induced LEE, and HBV/HCV coinfection. Medical records of ARV-naïve HIV-infected patients initiating ARV were reviewed for hepatitis coinfection, LEE (grade ≥2 AST/ALT) and changes in CD4 T-cell counts over time in an urban HIV clinic. Risk factors for LEE were statistically evaluated, and changes in CD4 T-cell counts were estimated by a mixed-effects linear model. Predictors of LEE included HBV/HCV coinfection (OR=6.44) and stavudine use (OR=2.33). Nelfinavir use was protective (OR=0.45). The mean rate of change in CD4 T-cell counts was higher in HBV/HCV coinfected subjects who developed LEE (99 cells/μL per month) compared with non-coinfected subjects who did not develop LEE (59 cells/μL per month, P=0.03), non-coinfected subjects who developed LEE (36 cells/μL per month, P=0.01), and coinfected subjects who did not develop LEE, 38% higher (62 cells/μL per month; P=0.11) A more robust immune restoration was observed among HBV/HCV coinfected subjects who developed liver enzyme elevation after antiretroviral initiation compared with other groups. This finding suggests that ARV-related liver enzyme elevation may be related in part to immune reconstitution, as measured by changes in CD4 T-cell counts.