Managing Symptomatic Drug-Induced Liver Injury in HIV–Hepatitis C Virus–Coinfected Patients: A Role for Interferon
1Lemuel Shattuck Hospital, 2Tufts University School of Medicine, 3Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, and 4Boston Medical Center, Boston, Massachusetts
Background. Human immunodeficiency virus (HIV)–infected patients with hepatitis C virus (HCV) coinfection are at increased risk for drug-induced liver injury (DILI) compared with patients with HIV infection alone. The mechanism underlying this observation is unknown. We hypothesized that interferon (IFN) would induce biochemical improvement through its anti-inflammatory properties and thereby facilitate the reintroduction of antiretroviral therapy (ART) in patients with DILI.
Methods. Patients with symptomatic DILI were referred for evaluation; biopsy of a liver sample was performed for all patients, except 1 with clinical cirrhosis.
Results. Twelve patients with acquired immunodeficiency syndrome and symptomatic grade 3/4 hepatotoxicity received treatment with IFN and ribavirin (RBV). Seven of these patients had a history of recurrent DILI. The mean baseline CD4+ T cell counts and HIV RNA levels were 124 cells/mm3 and 115,369 copies/mL, respectively. Biopsies of liver samples demonstrated significant necroinflammation (mean grade, 10.3) and fibrosis (mean stage, 2.9). Three patients continued to receive ART when they began treatment with IFN-RBV; 9 reinitiated ART within an average of 12 weeks (range, 4–20 weeks) of HCV treatment initiation. All patients attained marked improvement in aminotransferases and continued to receive ART treatment during a mean follow-up regimen of 26.5 months, with subsequent virologic suppression and immunologic reconstitution (mean CD4+ cell count increase, 251/mm3). However, only 1 patient maintained HCV suppression after completion of treatment with IFN-RBV.
Conclusions. In patients with symptomatic DILI, treatment with IFN-ribavirin (RBV) led to decreases in aminotransferase levels, which enabled the reinitiation of ART. The beneficial effects of IFN-based therapy may be modulated through the suppression of proinflammatory cytokines, even in virologic nonresponders. Herein, we propose a novel mechanism for DILI, whereby HCV- and HIV-associated inflammatory mediators induce liver injury synergistically.
Received 16 May 2007; accepted 11 July 2007; electronically published 15 October 2007.