Purpose: Chronic Hepatitis C viral (HCV) infection can result in fibrosis of the liver and cirrhosis. In North America, more than 70% of new infections occur in injection drug users (IDUs). Due to the morbidity and mortality associated with end-stage liver disease, understanding the natural history of chronic HCV in this population is essential to inform future health care policy. The purpose of this study was to estimate the rate of progression to cirrhosis for those infected with HCV through injection drug use.

Methods: Systematic review of the literature identified articles providing information on the mean duration of infection and the prevalence of cirrhosis for those who obtained HCV infection through injection drug use. Data on mean age, mean alanine aminotransferase (ALT) enzyme levels, proportion male, proportion with HIV co-infection, proportion with alcohol abuse, and study setting (liver clinic, community-based or addiction therapy) were abstracted. Summary progression rates were estimated using random effects Poisson meta-regression, fitted with WinBUGS software. Uninformative prior distributions were used. The impact of study co-variates on the progression rate was assessed by estimating the posterior probability that the relative risk (RR) exceeds 1.0.

Results: Systematic review identified 5,225 abstracts. Abstract review identified 460 relevant articles and a total of 40 articles met the inclusion criteria. The progression rate estimate (adjusted for all co-variates) was 6.0 per 1000 person-years (95% Credible Region, 2.0 to 12.0 per 1000 person-years) for community-based/addiction therapy populations corresponding to a 20-year cirrhosis prevalence of 11.3%. The progression rate derived from liver clinics was 1.5 times greater than the rate for community-based or addiction therapy settings (probability RR>1 = 0.74). Faster progression was associated with a greater proportion male and a greater proportion with excessive alcohol consumption, but not a greater proportion co-infected with HIV (probability RR>1 = 0.87, 0.93 and 0.52, respectively). Two studies (one with a large sample size) that demonstrated no difference in prognosis associated with HIV co-infection may explain this counterintuitive result.

Conclusions: Liver clinic studies produce estimates of faster progression rates than community-based or addiction therapy studies, likely due to referral bias. Disease models based on data from post-transfusion or liver clinic cohorts may overestimate future disease burden resulting from newly acquired HCV infections occurring predominantly in IDUs.