Angiotensin converting enzyme-2 and transforming growth factor beta-1 are over-expressed during fibrogenesis in liver tissue of patients with chronic hepatitis C virus infection

ABSTRACT

Hepatitis C virus [HCV] infection leads to chronic hepatitis which may eventually progress to cirrhosis and hepatocellular carcinoma. A significant relationship between inheritance of hightened expression of angiotensin II [A-2] and transforming growth factor beta [TGF-beta] and the development of progressive hepatic fibrosis has been noted. Recent studies have revealed that the renin angiotensin system [RAS] and the local RAS components are implicated in liver fibrogenesis and carcinogenesis. TGF-beta1 is a key cytokine in inflammation that regulates the production and deposition of extracellular matrix, directly stimulates angiogenesis and plays an important role in tumorigenesis. In this study we aimed to investigate the expression of angiotensin converting enzyme-2 [ACE-2] and TGF-beta1 in liver biopsies from patients with HCV infection alone or with hepatocellular carcinoma [HCC] on top of HCV cirrhosis. Liver biopsies from 40 patients with HCV infection and 20 patients with HCC on top of HCV-cirrhosis were included in this study. Semiquantitative immunohistochemical analyses were performed using ACE-2 and TGF-beta1 antibodies on paraffin embedded liver sections. Immunohistochemical results revealed that the immunoreactive score of ACE-2 and TGF-beta1 correlated significantly with the stage of fibrosis [p=0.05, p=0.001 respectively] and that TGF-beta1 correlated also with the histological activity index [p=0.05]. Liver tissue from HCC demonstrated enhanced and differential expression of both ACE-2 and TGF-beta1. Our data provide evidence for the implication of ACE.-2 and TGF-beta1 in liver fibrogenesis and carcinogenesis; a finding that might be of prognostic and therapeutic value