TRANSFORMING GROWTH FACTOR-BETA(1) IN AUTOIMMUNE HEPATITIS - CORRELATION OF LIVER-TISSUE EXPRESSION AND SERUM LEVELS WITH DISEASE-ACTIVITY

Background/Aims: Transforming growth factor-beta(1) (TGF-beta(1)) is c onsidered the most important mediator of hepatic fibrogenesis, At the same time, TGF-beta 1 is an immunosuppressive cytokine, Development of fibrosis, often rapid, is a characteristic of autoimmune hepatitis, a s is spontaneous systemic immunosuppression. The aim of our study was therefore to define the role of TGF-beta(1) in autoimmune hepatitis. M ethods/Results: Using the MV 1Lu bioassay, we found markedly elevated serum levels of TGF-beta(1) (median 109 ng/ml) in active autoimmune he patitis, which normalised when patients reached biochemical remission following immunosuppressive therapy (median 34 ng/ml; p=0.0001 compare d to active disease). With a newly established ELISPOT-assay for TGF-b eta(1)-producing cells, we could exclude an increase in TGF-beta(1)-pr oducing peripheral blood cells as a source of the elevated TGF-beta(1) . However, by in situ hybridisation and immunohistochemistry, we found strong TGF-beta(1) expression in the inflamed liver. Tn addition to n on-parenchymal and infiltrating cells, many hepatocytes showed strong staining for TGF-beta(1), TGF-beta(1) expression in the liver normalis ed in remission, yet was still somewhat increased in patients with bio chemical remission but remaining histological disease activity. Conclu sions: These results suggest that TGF-beta 1 is an important mediator in active autoimmune hepatitis. They support the theory that immunosup pressive therapy needs to be guided by histology, as prevention of the development of cirrhosis presumably requires near complete suppressio n of TGF-beta(1) in the liver; this is only found when there is no lon ger any histological evidence of inflammation.