Steatosis in chronic hepatitis C is associated with inflammation and accelerated fibrogenesis.

To assess the contribution of peroxisome proliferator‐activated receptor‐α and ‐γ to the pathogenesis of hepatitis C virus associated steatosis is unknown.

We measured peroxisome proliferator‐activated receptor (PPAR)‐α and ‐γ mRNA by quantitative polymerase chain reaction in liver biopsies of 35 genotype 1 and 22 genotype 3 infected patients and in Huh7 cells expressing hepatitis C virus 1b or 3a core protein.

PPAR‐α mRNA was significantly reduced in livers of patients with genotype 3 compared with genotype 1. Steatosis was associated to a decreased expression of PPAR‐α in genotype 1, but not in genotype 3. PPAR‐γ expression was significantly lower in genotype 3 compared with genotype 1 and steatosis was associated to decreased levels of PPAR‐γ, but only in genotype 1. There was no significant relationship between PPARs mRNA levels and liver activity or fibrosis. Expression of the hepatitis C virus 3a core protein was associated with an increase in triglyceride accumulation and with a significant reduction of PPAR‐γ mRNA compared with hepatitis C virus 1b.

The presence of steatosis and hepatitis C virus genotype 3 are both associated with a significant down‐regulation of PPARs. These receptors, and also additional factors, seem to play a role in the pathogenesis of hepatitis C virus‐associated steatosis.