Hepatitis C virus genotype 3: a genotype that is not ‘easy-to-treat’

Abstract

The efficacy of antiviral treatment depends on which of the seven genotypes (G1–G7) of hepatitis C virus (HCV) has infected the patient. Conventionally, clinicians regarded G2 and G3 infections as ‘easy-to-treat’: dual therapy with pegylated interferon and ribavirin produces a sustained virologic response in approximately 40–50% of patients with G1 infection, compared with 80% when analyses report combined data for G2 and G3 patients, which is standard practice in many clinical studies. However, sustained virologic response rates appear to be lower in certain subgroups of people infected with G3 compared with those with G2 or the general HCV-infected population. This review examines the growing evidence that factors related to the virus (e.g., baseline viral load and a rapid virologic response) and host characteristics (e.g., steatosis and fibrosis, metabolic syndrome, host polymorphisms and ethnicity) contribute to variations in therapeutic success in G3 HCV.

Keywords:

• cirrhosis
• genotype 2
• genotype 3
• hepatitis C virus
• rapid virologic response
• sustained virologic response

Acknowledgements

The authors would like to thank J Hopps and M Greener from Creston Health for their editorial assistance. Funding for the editorial services was provided by Gilead Sciences Ltd.

Financial & competing interests disclosure

M Buti reports fees for speaker and/or advisory roles from BMS, Boehringer Ingelheim, GlaxoSmithKline, Gilead, MSD and Novartis. R Esteban reports fees for speaker and/or advisory roles from Boehringer Ingelheim, BMS, Gilead, MSD and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• The sustained virologic response (SVR) rate with pegylated interferon (peg-IFN) and ribavirin is approximately 80% for G2 and G3, when results from the two genotypes are combined. Therefore, many clinicians regard G2 and G3 HCV as relatively ‘easy-to-treat’.

• SVR rates are probably not homogenous throughout the G3 cohort and the ‘approximately 80%’ figure may be an oversimplification.

• Classically, two HCV-related factors influence natural history and treatment response, at least in G1 infections, the most studied genotype: HCV subtype and viral load.

• Several studies show that patients infected with a high viral load of G3 achieve lower SVR rates. However, few studies investigate the efficacy of IFN-based therapies by G3 subtype, while no data stratify responses to direct-acting antivirals according to subtype.

• Several host factors influence HCV’s natural history and response to treatment, including: age, sex, ethnicity, obesity, levels of low-density lipoprotein-cholesterol, insulin resistance and the degree of liver damage.

• Differences in SVR between cirrhotic and non-cirrhotic patients have emerged for G3 in patients receiving peg-IFN and ribavirin as well as with the newer direct-acting antivirals.

• SNPs in IL28B are associated with spontaneous clearance and response to HCV treatment, but may be less important in determining virologic responses in G3 than G1.

• Achieving a rapid virologic response with peg-IFN and ribavirin is one of the most important factors predicting the likelihood of SVR.

• Robust, prospective studies are needed to characterize the factors that influence SVR rates in people infected with G3.