Systematic Review

Epidemiology and Response to Directacting Antiviral Therapy in Genotype 6 Chronic Hepatitis C Virus Infection

Panita Mettikanont; Chalermrat Bunchorntavakul; K. Rajender Reddy


Aliment Pharmacol Ther. 2019;49(5):492-505. 

In This Article

Abstract and Introduction


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.


Hepatitis C virus (HCV) infection is a major global health problem as it is one of the leading cause of cirrhosis and hepatocellular carcinoma (HCC). Aside from liver-related morbidity, HCV can also contribute to extrahepatic manifestations, such as mixed cryoglobulimenia, glomerulonephritis and a variety of autoimmune and lymphoproliferative disorders.[1,2] Although the prevalence and incidence rates of HCV have started to decrease in many countries after the introduction of universal blood donor screening, and more recently, effective antiviral therapies, HCV infection remains one of the major healthcare problem globally.[3,4] Based on WHO estimates, an estimated 71 million people worldwide currently have HCV infection (prevalence 0.5%-1%) with Eastern Mediterranean (2.3%) and Europe (1.5%) being the most prevalent regions; approximately 399 000 people die each year from HCV.[5]

Hepatitis C virus is categorised into six major genotypes and more than 60 subtypes. Each genotype has its own geographical distribution. The most prevalent GT (genotype) worldwide is GT1 accounting for 49.1% out of the total population. The second most common genotype worldwide is GT3 (17.9%), followed by GT4 and GT2 with a rate of 16.8% and 11% respectively. GT5 and GT6 are the least prevalent, which, together with GT4, are more pre-dominantly distributed in lower-income countries.[6,7,8] HCV GT6 is prevalent in Southeast Asia and certain parts of East Asia, in particular, southern China. HCV GT6 is the most genetically diverse as compared to the other five major genotypes.[9] It was recently subclassified into 24 subtypes, which accounted for 36% of all known 67 HCV subtypes.[10] The previously reported HCV genotypes of 7, 8 and 9 that are endemic in Southeast Asia have been re-classified as subtypes of GT6 (6c to 6l, also called 6c-l) by a Consensus panel.[11,12,13,14]

The American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) recommend all oral, direct-acting antiviral (DAA) therapy for genotype 6 based on relatively sparse data from clinical trials conducted in regions of the World where this genotype is underrepresented. To that end we set out to review the data from clinical trials and observational studies to best assess efficacy and safety of DAA therapy in a pre-dominantly Asia confined HCV genotype of 6.