No increase in the expression of key unfolded protein response genes in HCV genotype 3 patients with severe steatosis

Abstract

Although hepatic steatosis is common in patients infected with HCV, the mechanisms leading to cellular triglyceride retention are obscure. A role for the Unfolded Protein Response (UPR) has been postulated, either through its activation or dysfunction. In this study we set out to investigate the expression of key UPR genes in HCV genotype 3 patients with moderate to severe steatosis. RNA was extracted from liver obtained by percutaneous biopsy and key genes from the UPR were semi quantified using real-time PCR. We compared values in patients with minimal steatosis to those with high steatosis. Patients with high steatosis were younger (44.6±2.4 vs. 37.4±2.1, p<0.05) and had higher hepatic viral RNA loads (1.00±0.21 vs. 3.98±0.22, p<0.05). We found no significant difference in the expression of UPR genes, except for a small increase in EDEM1 in the high steatosis group (1.00±0.13 vs. 1.38±0.09, p<0.05). In conclusion, despite a four-fold greater concentration of HCV RNA in tissue with a high level of steatosis, we found no change in the expression of key UPR related genes, except for a only a modest up-regulation of EDEM1. Our data does not support a sustained change in expression of UPR genes in the steatogenesis of HCVGT3 infected human liver.