Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2021; 27(11): 1006-1021
Published online Mar 21, 2021. doi: 10.3748/wjg.v27.i11.1006
Genotype 3-hepatitis C virus’ last line of defense
Dorota Zarębska-Michaluk
Dorota Zarębska-Michaluk, Department of Infectious Diseases, Jan Kochanowski University, Kielce 25-369, Świętokrzyskie, Poland
Author contributions: Zarębska-Michaluk D contributed to the manuscript.
Conflict-of-interest statement: No conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Dorota Zarębska-Michaluk, Professor, Department of Infectious Diseases, Jan Kochanowski University, Żeromskiego 5, Kielce 25-369, Świętokrzyskie, Poland.
Received: January 11, 2021
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.

Keywords: Hepatitis C virus, Genotype 3, Antiviral treatment, Interferon, Direct-acting antivirals, Pangenotypic

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.