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Natural history of hepatitis C virus infection in HIV-infected individuals in the era of HAART: systematic review and meta-analysis
Presented by Hla Hla Thein, Canada.
Thein H.H.1, Yi Q.2, Dore G.3, Krahn M.4
1Toronto General Research Institute, University Health Network, Clinical Decision-Making and Health Care, Toronto, Canada, 2National Epidemiology and Surveillance, Canadian Blood Service, Ottawa, Canada, 3National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Viral Hepatitis Program, Sydney, Australia, 4University of Toronto, Departments of Medicine and Health Policy, Management and Evaluation and Faculty of Pharmacy, Toronto, Canada
Objectives: To estimate stage-specific hepatic fibrosis progression rates in HIV/hepatitis C virus (HCV) coinfected individuals, to examine potential heterogeneity between studies, and to investigate the impact of HIV on HCV disease progression.
Methods: A systematic review of published prognostic studies among HIV/HCV coinfected and HCV monoinfected individuals was undertaken. Inclusion criteria were:
i) HIV and HCV infections determined by serological assays;
ii) information about age at assessment of liver disease or HCV acquisition;
iii) duration of HCV infection; and
iv) histological fibrosis staging and/or clinical diagnosis of cirrhosis. Seventeen of 46 studies reviewed fulfilled the inclusion criteria. Annual stage-specific transition probabilities (F0→F1, F3→F4) are derived using the Markov maximum likelihood estimation method. A meta-analysis and a meta-regression were performed adjusting for covariates (age at/duration and mode of HCV infection, gender, alcohol, HCV genotype and RNA, CD4 count, HAART). Cirrhosis rates were compared in studies (n=14) reporting both HCV groups.
Results: Median (IQR) annual transition rates of the HIV/HCV coinfected individuals (82% injection drug users) were: F0→F1 0.127 (0.094, 0.181); F1→F2 0.129 (0.102, 0.148); F2→F3 0.163 (0.140, 0.187); and F3→F4 0.141 (0.098, 0.170). The probability of cirrhosis after 20 and 40 years was 23% and 75%, respectively. Male gender and HCV RNA positivity were significantly associated with more rapid progression from F1→F2, while younger age at HCV infection, non-genotype 1, CD4 count <400/uL at assessment, and HAART were associated with slower progression. The rate ratio (95% CI) of cirrhosis between HIV/HCV coinfection and HCV monoinfection was 2.0 (1.8, 2.6).
Conclusions: Our predicted estimates for cirrhosis in HIV/HCV coinfected individuals appear to be higher than published estimates for HCV monoinfection. This study improves on previous studies by using a method that does not require the assumption of constant transition rates between stages and taking into account the effects of clinical factors and HAART on disease progression.
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