Association of Increased Hepatitis C Virus (HCV)–Specific IgG and Soluble CD26 Dipeptidyl Peptidase IV Enzyme Activity with Hepatotoxicity after Highly Active Antiretroviral Therapy in Human Immunodeficiency Virus–HCV‐Coinfected Patients

Hepatotoxicity was investigated, using plasma collected before and during treatment, in 16 human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected patients who responded to highly active antiretroviral therapy (HAART), during a retrospective longitudinal study. Eleven patients experienced hepatotoxicity (i.e., a >3-fold increase in alanine aminotransferase level) while receiving HAART, including 4 patients with clinical hepatitis. Control subjects were 5 patients without hepatotoxicity. Markers of HCV-specific immune responses (HCV core-specific immunoglobulin G [IgG] antibody), T cell activation (soluble [s] CD26 dipeptidyl peptidase IV [DPP IV] enzyme activity), and inflammation (nitrate/nitrite and soluble tumor necrosis factor receptor I [sTNFRI] levels) were correlated with liver damage and immune reconstitution. All patients with hepatotoxicity had increased HCV core-specific IgG antibody and sCD26 (DPP IV) activity but did not have increased nitrate/nitrite or sTNFRI levels. Hepatotoxicity without clinical hepatitis was associated with increased CD8 T cell counts. Thus, hepatotoxicity in HIV-HCV-coinfected patients who respond to HAART is associated with increased HCV-specific immune responses and T cell activation.