SYSTEMATIC REVIEW AND META-ANALYSIS OF DIRECTLY OBSERVED THERAPY FOR TREATMENT OF HEPATITIS C

Purpose: The goal of hepatitis C treatment is to achieve sustained virologic response (SVR) to avoid disease-related sequelae such as hepatocellular carcinoma. Directly observed therapy (DOT), in which medication consumption is observed, may facilitate health care delivery in difficult-to-treat populations with high hepatitis prevalence, such as prisoners and individuals who inject drugs. We conducted a systematic review and meta-analysis to quantify the effect of DOT on treatment completion and SVR.  

Method: We conducted a search of published studies in the Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, and EMBASE along with references of relevant review articles and eligible studies, plus conference proceedings and websites of the American Association for the Study of Liver Diseases, European Association for the Study of the Liver, Asian Pacific Association for the Study of the Liver, and the American Gastroenterological Association. Two abstractors evaluated and coded eligible studies. We separately meta-analyzed randomized controlled trials (RCTs) and observational studies comparing DOT to standard care, defined as receipt of anti-viral agents without direct observation.  Single-arm studies were excluded from analysis. Outcomes of interest included SVR and treatment completion with regimen range of 24-48 weeks. 

Result: A total of 259 articles were identified; after reviewing abstracts, 26 articles were included for full text review. Six articles (4 RCTs and 2 observational studies) were included in the final analysis evaluating 1061 subjects, 353 of which were enrolled in RCTs and 708 in observational studies; within RCTs, 166 received DOT and 187 standard care while in observational studies, 331 received DOT and 377 standard care.  Studies were conducted in outpatient clinics or correctional institutions. Herein we report the results of random effects models. In observational studies, patients receiving DOT were significantly more likely to complete treatment (odds ratio (OR) 1.52, 95% CI 1.07-2.16, p=0.02) however in RCTs the odds of completing treatment were not significantly different comparing DOT to standard care (OR 2.21, 95% CI 0.78-6.29, p=0.14). Among RCT subjects, there was no significant difference in SVR between DOT and standard care (OR 1.36, 95% CI 0.62-3.00, p=0.44); similar findings were found in observational studies (OR 1.20, 95% CI 0.88-1.63, p=0.24). 

Conclusion: Directly observed therapy was beneficial for completion of treatment however only in the setting of observational studies; DOT did not impact SVR.