In vivo analysis at the cellular level reveals similar steatosis induction in both hepatitis C virus genotype 1 and 3 infections

摘要

Summary Steatosis is a frequent histological feature of hepatitis C virus ( HCV ) infection. Cohort studies of patients with chronic hepatitis C identified HCV genotype 3 ( HCV GT 3) as the prevalent steatotic genotype. Moreover, Huh‐7 cells over‐expressing HCV GT 3 core protein accumulate more triglyceride in larger lipid droplets than cells expressing core proteins of other HCV genotypes. However, little is known about the relationship of steatosis and HCV infection at the cellular level in vivo. In this study, we used highly sensitive multiplex in situ hybridization methodology together with lipid staining to investigate HCV ‐induced lipid droplet accumulation at the cellular level in liver biopsies. Consistent with previous reports, histological steatosis grades were significantly higher in GT 3 compared to GT 1 infected livers, but independent of viral load. Using nile red lipid stainings, we observed that the frequency of lipid droplet containing cells was similar in HCV GT 1‐ and HCV GT 3‐infected livers. Lipid droplet formation preferentially occurred in HCV ‐infected cells irrespective of the genotype, but was also observed in noninfected cells. These findings demonstrate that the main difference between GT 1‐ and GT 3‐induced steatosis is the size of lipid droplets, but not the number or relative distribution of lipid droplets in infected vs uninfected hepatocytes.