Reduced heme oxygenase-1 expression in steatotic livers infected with hepatitis C virus

Hepatic nonalcoholic fatty liver disease (NAFLD) is known to exacerbate liver injury due to chronic hepatitis C infection. Heme oxygenase-1 (HO-1) is an important protective antioxidative defense enzyme that is known to be induced in response to NAFLD and other liver injuries. The aim of this study was to evaluate HO-1 expression in HCV infected human livers with concomitant NAFLD. Methods: We compared levels of HO-1 in NAFLD liver biopsies from patients with or without chronic HCV infection using immunohistochemistry, immunoblots and real time RT-PCR. We also evaluated frozen sections of liver with dihydroethidium (DHE) or dichlorofluorescein (DCF) fluorescence staining to evaluate O₂^- and peroxide production respectively. Results: HO-1 expression was only increased in NAFLD livers without HCV infection, while HCV infected livers showed reduced HO-1 levels, regardless whether NAFLD was present. In uninfected livers with NAFLD, HO-1 expression was primarily localized in hepatocytes containing fat and areas of injury around the central vein. However, both NAFLD with and without concomitant HCV infection showed high levels of O₂^- or peroxide production compared to normal human liver control samples. Conclusions: These findings support the hypothesis that NAFLD is an important process for hepatocyte oxidative stress and injury in liver diseases. They also suggest that HCV can repress HO-1 induction in vivo even when other inducers of HO-1 are present.