<Emphasis Type="Bold">Background and Objective: In developed countries, injection drug users have the highest prevalence and incidence of hepatitis C virus (HCV) infection. Clinicians and policy makers have several options for reducing morbidity and mortality related to HCV infection, including preventing new infections, screening high-risk populations, and optimizing uptake and delivery of antiviral therapy. Cost-effectiveness analyses provide an estimate of the value for money associated with adopting healthcare interventions. Our objective was to determine the cost effectiveness of hepatitis C interventions (prevention, screening, treatment) targeting substance users and other groups with a high proportion of substance users. <Emphasis Type="Bold">Methods: We conducted a systematic search of MEDLINE, EMBASE, CINAHL, HealthSTAR and EconLit, and the grey literature. Studies were critically appraised using the Drummond and Jefferson, Neumann et al. and Philips et al. checklists. We developed and applied a quality appraisal instrument specific to cost-effectiveness analyses of HCV interventions. In addition, we summarized cost-effectiveness estimates using a single currency and year ($US, year 2009 values). <Emphasis Type="Bold">Results: Twenty-one economic evaluations were included, which addressed prevention (three), screening (ten) and treatment (eight). The quality of the analyses varied greatly. A significant proportion did not incorporate important aspects of HCV natural history, disease costs and antiviral therapy. Incremental cost-effectiveness ratios (ICERs) ranged from dominant (less costly and more effective) to $US603 352 per QALY. However, many ICERs were less than $US100 000 per QALY. Screening and treatment interventions involving pegylated interferon and ribavirin were generally cost effective at the $US100000 per QALY threshold, with the exception of some subgroups, such as immune compromised patients with genotype 1 infections. <Emphasis Type="Bold">Conclusions: No clear consensus emerged from the studies demonstrating that prevention, screening or treatment provides better value for money as each approach can be economically attractive in certain subgroups. More high-quality economic evaluations of preventing, identifying and treating HCV infection in substance users are needed. Copyright Springer International Publishing AG 2012
