BACKGROUND/AIMS: Transforming growth factor-beta1 (TGF-beta1) is considered the most important mediator of hepatic fibrogenesis. At the same time, TGF-beta1 is an immunosuppressive cytokine. Development of fibrosis, often rapid, is a characteristic of autoimmune hepatitis, as is spontaneous systemic immunosuppression. The aim of our study was therefore to define the role of TGF-beta1 in autoimmune hepatitis. METHODS/ RESULTS: Using the MV 1Lu bioassay, we found markedly elevated serum levels of TGF-beta1 (median 109 ng/ml) in active autoimmune hepatitis, which normalised when patients reached biochemical remission following immunosuppressive therapy (median 34 ng/ml; p=0.0001 compared to active disease). With a newly established ELISPOT-assay for TGF-beta1-producing cells, we could exclude an increase in TGF-beta1-producing peripheral blood cells as a source of the elevated TGF-beta1. However, by in situ hybridisation and immunohistochemistry, we found strong TGF-beta1 expression in the inflamed liver. In addition to non-parenchymal and infiltrating cells, many hepatocytes showed strong staining for TGF-beta1. TGF-beta1 expression in the liver normalised in remission, yet was still somewhat increased in patients with biochemical remission but remaining histological disease activity. CONCLUSIONS: These results suggest that TGF-beta1 is an important mediator in active autoimmune hepatitis. They support the theory that immunosuppressive therapy needs to be guided by histology, as prevention of the development of cirrhosis presumably requires near complete suppression of TGF-beta1 in the liver; this is only found when there is no longer any histological evidence of inflammation.
BACKGROUND/AIMS: Transforming growth factor-beta1 (TGF-beta1) is considered the most important mediator of hepatic fibrogenesis. At the same time, TGF-beta1 is an immunosuppressive cytokine. Development of fibrosis, often rapid, is a characteristic of autoimmune hepatitis, as is spontaneous systemic immunosuppression. The aim of our study was therefore to define the role of TGF-beta1 in autoimmune hepatitis. METHODS/ RESULTS: Using the MV 1Lu bioassay, we found markedly elevated serum levels of TGF-beta1 (median 109 ng/ml) in active autoimmune hepatitis, which normalised when patients reached biochemical remission following immunosuppressive therapy (median 34 ng/ml; p=0.0001 compared to active disease). With a newly established ELISPOT-assay for TGF-beta1-producing cells, we could exclude an increase in TGF-beta1-producing peripheral blood cells as a source of the elevated TGF-beta1. However, by in situ hybridisation and immunohistochemistry, we found strong TGF-beta1 expression in the inflamed liver. In addition to non-parenchymal and infiltrating cells, many hepatocytes showed strong staining for TGF-beta1. TGF-beta1 expression in the liver normalised in remission, yet was still somewhat increased in patients with biochemical remission but remaining histological disease activity. CONCLUSIONS: These results suggest that TGF-beta1 is an important mediator in active autoimmune hepatitis. They support the theory that immunosuppressive therapy needs to be guided by histology, as prevention of the development of cirrhosis presumably requires near complete suppression of TGF-beta1 in the liver; this is only found when there is no longer any histological evidence of inflammation.
Authors: Anne-Charlotte de Gouville; Valerie Boullay; Gael Krysa; Julia Pilot; Jean-Marie Brusq; Florence Loriolle; Jean-Michel Gauthier; Stephen A Papworth; Alain Laroze; Françoise Gellibert; Stephane Huet Journal: Br J Pharmacol Date: 2005-05 Impact factor: 8.739
Authors: Amal K Dutta; Kristy Boggs; Al-Karim Khimji; Yonas Getachew; Youxue Wang; Charles Kresge; Don C Rockey; Andrew P Feranchak Journal: Am J Physiol Gastrointest Liver Physiol Date: 2020-02-24 Impact factor: 4.052
Authors: Ji Young Son; Song Yee Kim; Sang Ho Cho; Hyo Sub Shim; Ji-Ye Jung; Eun Young Kim; Ju Eun Lim; Byung Hoon Park; Young Ae Kang; Young Sam Kim; Se Kyu Kim; Joon Chang; Moo Suk Park Journal: Lung Date: 2013-01-24 Impact factor: 2.584