Impact of the combined low dose prednisolone regimen on liver fibrosis in children with autoimmune hepatitis who responded to treatment

Autoimmune hepatitis [AIH] is a chronic liver disease characterized histologically by interface hepatitis. Hepatic fibrosis and cirrhosis can occur in many types of chronic liver injury including AIH. Recent studies have reported that hepatic fibrosis and cirrhosis may be reversible in some patients with AIH who respond to treatment. To assess the effects of treatment on fibrosis in liver biopsies of children with AIH who responded to the combined low dose prednisolone and azathioprine regimen. Twenty children with median age 8 +/- 3.5 yrs [9 girls, 11 boys], 18 AIH type I and two AIH type II, who were in clinical and biochemical remission for at least 6 months, and who had a diagnostic and a follow-up liver biopsy were included in this study. Different histological stains were used for assessing the grade of necroinflammatory activity [HAI] and for evaluating the stage of fibrosis according to Ishak scoring system. Morphometric analysis using LeicaQ500IS image analyzer was applied on Peri's stained liver sections to assess the percentage of liver fibrosis. Data revealed significant decrease in the median HAI from 8.85 to 3.6 [p=0.001]. The median fibrosis score showed significant reduction from 3.9 to 2.4 [p=0.001] and the median fibrosis percentage decreased from 28.7 to 12.8 [p=0.001]. These data provide evidence for regression of fibrosis in AIH in children who responded to the combined low dose immunosuppressive prednisolone and azothioprine regimen. Fibrosis control is associated with regression of necroinflammatory activity, which is the main treatment component in AIH

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

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