Update on hepatitis C virus management

Abstract

There are around 130-150 million chronic hepatitis C virus (HCV) carriers globally, leading to an annual mortality of 500 000. Asia has the largest HCV population in the world, with China alone having more HCV-infected persons than Europe and America taken together. The incidence of HCV genotype 6 was first identified in a collaborative study between Hong Kong and Scotland, being around 27%. Subsequently it is shown that Vietnam and Myanmar have the highest incidences of HCV genotype 6, 36-49%. The transmission of genotype 6 is predominantly through intravenous drug use. The first study of the treatment of HCV, with the traditional interferon for 6 months, was published in 1986. In three decades, with the arrival of the direct-acting antivirals (DAAs), the CURE rate for HCV-infected patients (that is sustained response for >12 weeks after treatment) has increased from 6% to 95-100% with 12 weeks of oral treatment. The goal of treatment is obviously to reduce all-cause mortality. Meta-analysis of interferon treatment shows that sustained responders have a lower rate of cirrhosis progression as well as development of hepatocellular carcinoma. Another encouraging finding is that late relapses after 4-5 years of follow-up occur in only 1-2%. Long-term follow-up data for DAAs are yet to be published. The licensed agents for the treatment of HCV genotype 1 and 4 include: Harvoni (a single table combining ledispasvier, a NS5A inhibitor, and sofosbuvir, a NS5B inhibitor); Viekira pak (4 tablets combining dasabuvir, a NS5B inhibitor, ombitasvir, aNS5A inhibitor, and paritaprevir, a protease inhibitor which has to be potentiated by ritonavir, a P450 inhibitor); Zepatier (a single tablet combining grazapatier, a protease inhibitor, and elbasivir, a NS5A inhibitor). Harvoni is also licensed for genotypes 5 and 6. A pan-genotypic drug was licensed in 2016. This drug is Epclusa, a single tablet combination of sofosbuvir and velpatasvir, another NS5A inhibitor. With Epclusa, the cure rate for genotypes 1, 2, 4, 5, and 6 is 99-100%; and for the most difficult-to-treat genotype 3, still 95%. No change in regimen is required with the occurrence of resistance-associated polymorphisms for most of these drugs, except for Zepatier where a 16-week course is required. The main problems still existing for the eradication of HCV are: the very high cost of the treatment, the lack of awareness of the infection in the general population, and the possibility of re-infection with continued intravenous drug use.