Managing symptomatic drug-induced liver injury in HIV-hepatitis C virus-coinfected patients: a role for interferon.
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/mm(3) 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/mm(3)). 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.
McGovern
Barbara H
BH
Lemuel Shattuck Hospital, Jamaica Plain, MA 02130, USA. bmcgovern@tufts-nemc.org
Birch
Christopher
C
Zaman
M Tauheed
MT
Bica
Ioana
I
Stone
David
D
Quirk
James R
JR
Davis
Benjamin
B
Zachary
Kimon
K
Basgoz
Nesli
N
Graeme-Cook
Fiona
F
Gandhi
Rajesh T
RT
D019380:Anti-HIV Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D001706:Biopsy; D018791:CD4 Lymphocyte Count; D056486:Chemical and Drug Induced Liver Injury; D005260:Female; D006678:HIV / Q000302:isolation & purification; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy*; D008297:Male; D009336:Necrosis / Q000473:pathology; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000627:therapeutic use; D000637:Transaminases / Q000097:blood; D019562:Viral Load
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D012367:RNA, Viral; D012254:Ribavirin; D007372:Interferons; D000637:Transaminases