Published online Mar 21, 2021. doi: 10.3748/wjg.v27.i11.1006
Peer-review started: January 11, 2021
First decision: January 23, 2021
Revised: January 24, 2021
Accepted: February 28, 2021
Article in press: February 28, 2021
Published online: March 21, 2021
Chronic infection with hepatitis C virus (HCV) is one of the leading causes of liver disease globally, affecting approximately 71 million people. The majority of them are infected with genotype (GT) 1 but infections with GT3 are second in frequency. For many years, GT3 was considered to be less pathogenic compared to other GTs in the HCV family due to its favorable response to interferon (IFN)-based regimen. However, the growing evidence of a higher rate of steatosis, more rapid progression of liver fibrosis, and lower efficacy of antiviral treatment compared to infection with other HCV GTs has changed this conviction. This review presents the specifics of the course of GT3 infection and the development of therapeutic options for GT3-infected patients in the era of direct-acting antivirals (DAA). The way from a standard of care therapy with pegylated IFN-alpha (pegIFNα) and ribavirin (RBV) through a triple combination of pegIFNα + RBV and DAA to the highly potent IFN-free pangenotypic DAA regimens is discussed along with some treatment options which appeared to be dead ends. Although the implementation of highly effective pangenotypic regimens is the most recent stage of revolution in the treatment of GT3 infection, there is still room for improvement, especially in patients with liver cirrhosis and those who fail to respond to DAA therapies, particularly those containing inhibitors of HCV nonstructural protein 5A.
Core Tip: Genotype 3 which is second in frequency worldwide, is unique among genotypes of hepatitis C virus in its higher rate of steatosis, accelerated fibrosis progression, and lower cure rates. This paper describes the genotype-specific mechanisms of liver injury and provides an overview of therapeutic options. Currently, available highly potent pangenotypic regimens have revolutionized the treatment of genotype 3 infection, however, patients with liver cirrhosis and those who fail to response to direct-acting antiviral therapy still present a therapeutic challenge.