Published estimates of liver fibrosis progression in individuals with chronic hepatitis C virus (HCV) infection are heterogeneous. We aimed to estimate stage-specific fibrosis progression rates and their determinants in these individuals. A systematic review of published prognostic studies was undertaken. Study inclusion criteria were as follows: (1) presence of HCV infection determined by serological assays; (2) available information about age at assessment of liver disease or HCV acquisition; (3) duration of HCV infection; and (4) histological and/or clinical diagnosis of cirrhosis. Annual stage-specific transition probabilities (F03 F1, . . . , F33 F4) were derived using the Markov maximum likelihood estimation method and a meta-analysis was performed. The impact of potential covariates was evaluated using meta-regression. A total of 111 studies of individuals with chronic HCV infection (n β«Ψβ¬ 33,121) were included. Based on the random effects model, the estimated annual mean (95% confidence interval) stage-specific transition probabilities were: F03 F1 0.117 (0.104-0.130); F13 F2 0.085 (0.075-0.096); F23 F3 0.120 (0.109-0.133); and F33 F4 0.116 (0.104-0.129). The estimated prevalence of cirrhosis at 20 years after the infection was 16% (14%-19%) for all studies, 18% (15%-21%) for cross-sectional/ retrospective studies, 7% (4%-14%) for retrospective-prospective studies, 18% (16%-21%) for studies conducted in clinical settings, and 7% (4%-12%) for studies conducted in nonclinical settings. Duration of infection was the most consistent factor significantly associated with progression of fibrosis. Conclusion: Our large systematic review provides increased precision in estimating fibrosis progression in chronic HCV infection and supports nonlinear disease progression. Estimates of progression to cirrhosis from studies conducted in clinical settings were lower than previous estimates. (HEPATOLOGY 2008;48:418-431.)
H epatitis C virus (HCV) is the most common cause of end-stage liver disease and the leading indication for liver transplantation. 1 Although chronic HCV infection can progress slowly to liver fibrosis and the subsequent development of cirrhosis, liver failure, and hepatocellular carcinoma, progression can also be rapid. Some published reports suggest that the prognosis of HCV is benign, with only 2%-3% developing cirrhosis at 20 years after infection. [2][3][4] Other reports suggest that the prognosis is much worse, with 51% of patients developing cirrhosis at 22 years. 5 Consequently, the true prognosis of HCV infection is still beset by controversy. Previous studies have explored the effect of study design, setting, study population, and methods used to estimate fibrosis progression as potential sources of variability among published estimates of prognosis. 6-8 A previous systematic review and meta-analysis by Freeman et al. 6 have shown varying progression rates among different populations. In their review, higher rates of progression to cirrhosis were reported for posttransfusion cohorts and cross-sectional liver clinic series, and much lower rates for