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HIV and hepatitis C coinfection: pathogenesis and microbial translocation

Page, Emma E.a,b; Nelson, Markb; Kelleher, Petera,b

doi: 10.1097/COH.0b013e32834bbc71
HIV and hepatitis C coinfection: Edited by Jurgen Rockstroh and Gail Matthews

Purpose of review: Human immune deficiency virus (HIV)-1 and hepatitis C virus (HCV) coinfected individuals progress more rapidly to fibrosis than their HCV mono-infected counterparts. Increased microbial translocation in HIV-1/HCV coinfection may play an important role.

Recent findings: The mechanisms of accelerated liver fibrosis in HIV-1/HCV coinfection are complex. Products of microbial translocation may promote liver fibrosis either by direct interaction with Kupffer cells and hepatic stellate cells (HSCs) or indirectly via induction of systemic immune activation and activation-induced apoptotic cell death. HIV-1 enteropathy is associated with increased microbial translocation and systemic immune activation. Mechanisms that underlie increased microbial translocation include direct effects of HIV-1 infection on epithelial barrier function and alteration in intestinal permeability secondary to inflammatory cytokines and CD4 T-cell depletion. Risk of liver fibrosis is increased in HIV-1/HCV coinfection and associated with reduced CD4 T-cell counts and raised lipopolysaccharide levels and/or depletion of hepatic Kupffer cells.

Summary: Large-scale longitudinal clinical studies are needed to confirm the importance of microbial translocation in promotion of hepatic fibrosis. If microbial translocation is a significant contributory factor to hepatic fibrosis, targeted interventions against microbial products may improve clinical outcomes.

aImmunology Section, Division of Infectious Diseases, Imperial College London

bSexual Health and HIV Medicine, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK

Correspondence to Dr Emma E. Page, Immunology Department, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK Tel: +44 2033155979; e-mail: e.page09@imperial.ac.uk

© 2011 Lippincott Williams & Wilkins, Inc.