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NATURAL HISTORY OF HEPATITIS C IN HIV-INFECTED INDIVIDUALS AND THE IMPACT OF HIV IN THE ERA OF HAART: A META-ANALYSIS
HH Thein1, Q Yi2, GJ Dore3, MD Krahn1
1University Health Network and University of Toronto, Toronto, Ontario; 2National Epidemiology and Surveillance, Canadian Blood Service, Ottawa, Ontario; 3National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Sydney, NSW, Australia
The natural history of hepatitis C virus (HCV) in HIV-infected individuals in the era of highly active antiretroviral therapy (HAART) is unclear. We aimed to estimate stage-specific transition probabilities in individuals with HIV/HCV coinfection, examine the effect of covariates on these rates and investigate the effect of HIV on HCV-related cirrhosis in the era of HAART.
Our systematic review included studies reporting: 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; iv) histological fibrosis staging (F0-F4) and/or clinical diagnosis of cirrhosis; and v) comparison between HCV monoinfected and HIV/HCV coinfected populations. Annual stage-specific transition probabilities were derived using the Markov maximum likelihood estimation (MMLE) method. A meta-analysis was performed to estimate pooled transition probabilities among studies meeting inclusion criteria (n = 17). A meta-regression was performed to investigate the impact of covariates, including clinical factors and HAART on fibrosis progression rates. Risk of cirrhosis in HAART and non-HAART groups were compared (n = 27).
The estimated mean (95% CI) annual transition rates of the HIV/HCV coinfected individuals were: F0—>F1 0.122 (0.098-0.153); F1—>F2 0.115 (0.095-0.140); F2—>F3 0.124 (0.097-0.159); and F3—>F4 0.115 (0.098- 0.135). The estimated cumulative probability of cirrhosis after 20 years of HCV infection was 21% (95% CI, 16%-28%). Male gender (Adjusted relative risk, Adj. RR 5.70, 95% CI, 1.12-28.87), acquisition of HCV infection via blood transfusion (Adj. RR 12.28, 95% CI, 1.26-119.69), and excess alcohol intake (Adj. RR 2.98, 95% CI, 1.28-6.91) were independently associated with more rapid fibrosis progression. Injecting drug use was significantly associated with a slower rate of fibrosis progression (Adj. RR 0.34, 95% CI, 0.87-0.96). The rate ratio (95% CI) of cirrhosis between HIV/HCV coinfected and HCV monoinfected individuals was 2.1 (1.5-3.0) for all patients: 2.5 (1.8-3.4) in the non-HAART group; and 1.8 (1.1-2.8) in the HAART group.
Our study found that chronic hepatitis C outcomes are worse among coinfected patients. Over the period studied, HAART did not appear to fully correct the adverse effect of HIV infection on HCV prognosis.