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People detained in prisons and other closed settings are at elevated risk of infection with hepatitis C virus (HCV). We undertook a systematic review and meta-analysis with the aim of determining the rate of incident HCV infection and the prevalence of anti-HCV among detainees in closed settings. We systematically searched databases of peer-reviewed literature and widely distributed a call for unpublished data. We calculated summary estimates of incidence and prevalence among general population detainees and detainees with a history of injection drug use (IDU), and explored heterogeneity through stratification and meta-regression. The summary prevalence estimates were used to estimate the number of anti-HCV positive prisoners globally. HCV incidence among general detainees was 1.4 per 100 person-years (py; 95% confidence interval [CI]: 0.1, 2.7; k = 4), and 16.4 per 100 py (95% CI: 0.8, 32.1; k = 3) among detainees with a history of IDU. The summary prevalence estimate of anti-HCV in general detainees was 26% (95% CI: 23%, 29%; k = 93), and in detainees with a history of IDU, 64% (95% CI: 58%, 70%; k = 51). The regions of highest prevalence were Central Asia (38%; 95% CI 32%, 43%; k = 1) and Australasia (35%; 95% CI: 28%, 43%; k = 9). We estimate that 2.2 million (range: 1.4-2.9 million) detainees globally are anti-HCV positive, with the largest populations in North America (668,500; range: 553,500-784,000) and East and Southeast Asia (638,000; range: 332,000-970,000). Conclusion: HCV is a significant concern in detained populations, with one in four detainees anti-HCV-positive. Epidemiological data on the extent of HCV infection in detained populations is lacking in many countries. Greater attention towards prevention, diagnosis, and treatment of HCV infection among detained populations is urgently required. (Hepatology 2013;58:1215–1224)