ESTIMATION OF FIBROSIS PROGRESSION RATES FOR CHRONIC HEPATITIS C: A SYSTEMATIC REVIEW AND META-ANALYSIS UPDATE
Purpose: Chronic Hepatitis C viral infection (HCV) is a leading cause of cirrhosis, liver failure, cancer and transplantation, making it a major medical and economic burden. Given the recent availability of highly effective but costly antivirals for HCV, identifying individual with advanced disease or rapid disease progression has become important for informing treatment prioritization. Moreover, accurate estimation of HCV-disease progression is also essential for evaluating the cost effectiveness of treatment. The purpose of this study was to obtain the most up-to-date stage-specific and stage-constant liver fibrosis progression rates (FPR) in individuals with chronic HCV infection though an updated systematic review and meta-analysis.
Methods: Literature search was conducted using MEDLINE, EMBASE and PubMed databases covering a period from January 1990 to August 2014 and supplemented by reference and citation searches. In general, the review included published English and non-English peer-reviewed prognostic studies which examine liver fibrosis progression in HCV-infected individuals with no HCV treatment. Publication bias was assessed by Funnel plots and Egger's test for asymmetry. Stage-constant FPRs were estimated for each study via the indirect method using the fibrosis score distribution and the estimated duration of infection reported in each study. Stage-specific FPRs (F0-1, F1-2 F2-3, F3-4) were estimated using the Markov Maximum Likelihood estimation (MMLE) method developed by Yi et al. Random effects meta-analyses were used to obtain pooled stage constant and stage-specific FPR estimates.
Results: Overall, the updated systematic review included a total of 155 reports of HCV-infected individuals (n=53,412). Based on the random effects model, the pooled stage-constant FPR estimates derived through the indirect method were 0.103 (95%CI, 0.098-0.0108) METAVIR units per year. The stage-specific FPRs were F0-1: 0.113 (95%CI, 0.103-0.124); F1-2: 0.086 (95%CI, 0.078-0.094); F2-3:0.118 (95%CI, 0.108-0.129); F3-4: 0.115 (95%CI, 0.104-0.127) (Table 1).
Conclusion: The most recent pooled estimates are consistent with the original study covering the period from January 1990 to August 2007but suggest a slightly slower disease progression for stage-specific FPRs.