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.
Stone
Shelley F
SF
Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, and Department of Pathology, University of Western Australia, Perth, Australia. Shelley.Stone@health.wa.gov.au
Lee
Silvia
S
Keane
Niamh M
NM
Price
Patricia
P
French
Martyn A
MA
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000201:enzymology*; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D007109:Immunity / Q000187:drug effects; D007074:Immunoglobulin G / Q000276:immunology*; D008099:Liver / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D012995:Solubility
D019380:Anti-HIV Agents; D007074:Immunoglobulin G; D018819:Dipeptidyl Peptidase 4