Background and aims Extrahepatic manifestations of HCV are responsible for morbidity and mortality in many chronically infected patients. New, interferon-free antiviral treatment regimens, which present the opportunity to treat all HCV-infected patients, call for a better understanding of the benefits of treating non-cirrhotic chronically infected individuals.
Methods A systematic review was conducted. Identified studies from targeted database searches on Embase and Medline were screened. The methodological quality of the included publications was evaluated. Random-effect model meta-analyses were performed. Strength of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system.
Results Data were extracted from a total of 48 identified studies. Achieving sustained virological response (SVR) was associated with reduced extrahepatic mortality (vs no SVR, OR 0.44 (95% CI 0.28 to 0.67)). SVR was associated with higher complete remissions in patients with cryoglobulinemia vasculitis (OR 20.76 (6.73 to 64.05)) and a higher objective response in those with malignant B-cell lymphoproliferative diseases (OR 6.49 (2.02 to 20.85)). Achieving SVR was also associated with reduced insulin resistance at follow-up (OR 0.42 (0.33 to 0.53)) and a significant protective effect on the incidence of diabetes (OR 0.34 (0.21 to 0.56)). Lack of randomised data comparing SVR versus non-SVR patients for the relevant extrahepatic indications attenuated these analyses.
Conclusion Antiviral therapy can reduce extrahepatic manifestations related to HCV when SVR is achieved. Higher quality data, and reporting over longer follow-up periods, will be required to thoroughly explore comprehensive HCV treatment strategies.