Direct-acting Antiviral Regimens for Patients with Chronic Infection of Hepatitis C Virus Genotype 3 in China

Hepatitis C virus (HCV) genotype (GT)3 infection is associated with a more rapid hepatic disease progression than the other genotypes. Hence, early HCV clearance slows down the disease progression and is important for improving prognosis in GT3-infected patients. Nevertheless, compared with other genotypes, GT3 is difficult-to-treat with direct-acting antivirals, especially in the presence of cirrhosis. Current guidelines recommend several regimens which have been proven to be effective in GT3-infected patients from the Western world (North America, Europe, and Oceania). In China, GT3 infection comprises 8.7-11.7% of the 10 million patients infected with HCV and has strikingly different characteristics from that in Western countries. Unlike the Western countries, where GT3a is the predominant subtype, GT3a and 3b each affect roughly half of Chinese GT3-infected patients, with 94-96% of the GT3b-infected patients carrying A30K+L31M double NS5A resistance-associated substitutions. Phase 3 clinical trials including GT3b-infected patients have suggested that GT3b infection is difficult to cure, making the regimen choice for GT3b-infected patients an urgent clinical gap to be filled. This review includes discussions on the epidemiology of HCV GT3 in China, recommendations from guidelines, and clinical data from both Western countries and China. The aim is to provide knowledge that will elucidate the challenges in treating Chinese GT3-infected patients and propose potential solutions and future research directions.