Genotype 3 Infection: The Last Stand of Hepatitis C Virus

Abstract

Hepatitis C virus (HCV) represents a significant global disease burden, with an estimated 130-150 million people worldwide living with chronic HCV infection. Within the six major clinical HCV genotypes, genotype 3 represents 22-30% of all infection and is described as a unique entity with higher rates of steatosis, faster progression to cirrhosis, and higher rates of hepatocellular carcinoma. Hepatic steatosis in the setting of hepatitis C genotype 3 (HCV-3) is driven by viral influence on three major pathways: microsomal triglyceride transfer protein, sterol regulatory element-binding protein-1c, and peroxisome proliferator-associated receptor-α. Historically with direct-acting antivirals, the rates of cure for HCV-3 therapies lagged behind the other genotypes. As current therapies for HCV-3 continue to close this gap, it is important to be cognizant of common drug interactions such as acid-suppressing medication and amiodarone. In this review, we discuss the rates of steatosis in HCV-3, the mechanisms behind HCV-3-specific steatosis, and current and future therapies.

Figure 1

Global Prevalence of HCV Genotype 3

Figure 2

HCV-3 Viral Mediated Mechanisms of Steatosis. A) HCV-3 core inhibits MTTP affecting assembly of ApoB and lipid to VLDL. B) HCV-3 core induces the PI3K-Akt pathway, increasing activity of SREBP-1c and increasing FAS. C) HCV core increases levels of PPAR-α leading to hepatic lipid accumulation