Peroxisome proliferator-activated receptor-alpha and -gamma rnRNA levels are reduced in chronic hepatitis C with steatosis and genotype 3 infection

Background Steatosis in chronic hepatitis C is associated with inflammation and accelerated fibrogenesis. Aim To assess the contribution of peroxisome proliferator-activated receptor, alpha and -gamma to the pathogenesis of hepatitis C virus associated steatosis is unknown. Methods We measured peroxisome proliferator- activated receptor (PPAR)-alpha. and -gamma 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. Results PPAR-a mRNA was significantly reduced in livers of patients with genotype 3 compared with genotype 1. Steatosis was associated to a decreased expression of PPAR-alpha in genotype 1, but not in genotype 3. PPAR-gamma expression was significantly lower in genotype 3 compared with genotype 1 and steatosis was associated to decreased levels of PPAR-gamma, 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-gamma mRNA compared with hepatitis C virus 1b. Conclusions 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.