Systematic review: epidemiology and response to direct‐acting antiviral therapy in genotype 6 chronic hepatitis C virus infection

Summary Background Hepatitis C virus (HCV) genotype 6 (GT6) is predominantly encountered in Southeast Asia and data on GT6 response to direct‐acting antiviral (DAA) therapy are relatively limited. Aim To review the epidemiology and virologic outcome of DAA regimens in HCV GT6 patients. Methods Electronic literature search of PubMed, EMBASE, and The Cochrane Library databases were conducted. Results Hepatitis C virus genotype 6 is the most genetically diverse, has a prevalence of 19.9%‐95.6% in HCV infected patients in Southeast Asia and has been associated with a higher risk of HCC in those with cirrhosis. After an extensive literature review, a total of 20 studies were selected to assess study population and treatment outcomes (total of 938 GT6 patients were included); 12 were clinical trials and eight were observational studies. Sustained virologic response at week 12 (SVR 12) following glecaprevir/pibrentasvir (n = 4; 108 patients), ledipasvir/sofosbuvir (n = 8; 427 patients), sofosbuvir/velpatasvir with or without voxilaprevir (n = 5; 171 patients), sofosbuvir/daclatasvir (n = 3; 172 patients) and sofosbuvir with ribavirin (n = 3; 60 patients) was 98%‐100%, 64%‐100%, 100%, 88%‐94% and 100%, respectively. Failure was mostly in those with cirrhosis and prior treatment experience. DAA therapy was well tolerated and with a serious adverse event rate of <5%. Conclusions Hepatitis C virus genotype 6 is genetically diverse and is highly prevalent in Asia. While SVR rates have been high, cirrhosis and prior treatment experience marginally compromise response to DAAs. Large scale and exclusive studies in HCV genotype 6 prevalent areas are needed, while the current evidence suggests that DAAs are highly effective and safe.