Effect of Interferon-Gamma on Hepatic Fibrosis in Chronic Hepatitis B Virus Infection: A Randomized Controlled Study Hong-Lei Weng, Bao-En Wang, Ji-Dong Jia, Wan-Fen Wu, Jian-Zhong Xian, Peter R. Mertens, Wei-Min Cai, Steven Dooley Clinical Gastroenterology and Hepatology Volume 3, Issue 8, Pages 819-828 (August 2005) DOI: 10.1016/S1542-3565(05)00404-0 Copyright © 2005 American Gastroenterological Association Terms and Conditions
Figure 1 Trial design. Schematic outline of assessment/recruitment for patient eligibility and assignment to treatment groups. Clinical Gastroenterology and Hepatology 2005 3, 819-828DOI: (10.1016/S1542-3565(05)00404-0) Copyright © 2005 American Gastroenterological Association Terms and Conditions
Figure 2 Assessment of therapeutic efficacy by sequential histologic evaluation in control vs IFN-γ group. Each pair of liver biopsy specimens (baseline and after 9 months) were assessed with a semiquantitative scoring system and ranked accordingly. Clinical Gastroenterology and Hepatology 2005 3, 819-828DOI: (10.1016/S1542-3565(05)00404-0) Copyright © 2005 American Gastroenterological Association Terms and Conditions
Figure 3 Detailed histologic analysis. (A) Total inflammatory scores of individual patients over time. (B) Total fibrosis scores of individual patients in both groups over time. Patients with identical changes over time are indicated as one line only. Clinical Gastroenterology and Hepatology 2005 3, 819-828DOI: (10.1016/S1542-3565(05)00404-0) Copyright © 2005 American Gastroenterological Association Terms and Conditions
Figure 4 Morphology of IFN-γ-dependent changes in inflammation and fibrosis. Representative liver biopsy samples before and after IFN-γ treatment. (A, B) Inflammation is significantly reduced after IFN-γ treatment. Hematoxylin-eosin staining; original magnification 100×. (C, D) Fibrosis is significantly reduced after IFN-γ treatment. Masson trichrome staining; original magnification 40×. (E, F) Number of activated HSCs decreased significantly after IFN-γ treatment. Immunohistochemistry with anti α-SMA antiserum; original magnification 100×. (G, H) Immunohistochemistry with an antiserum against a phospho-peptide, PS2, that specifically recognizes phosphorylated Smad2. Positive staining (brown) was found in most nuclei of hepatocytes (G, red arrow) and was significantly decreased after 9 months of IFN-γ treatment. A few hepatocytes of IFN-γ treated patients displayed positive cytoplasmic staining (H, black arrow); original magnification 400×. Clinical Gastroenterology and Hepatology 2005 3, 819-828DOI: (10.1016/S1542-3565(05)00404-0) Copyright © 2005 American Gastroenterological Association Terms and Conditions
Figure 5 Serum fibrosis and liver function indices in IFN-γ treated and control patients, with and without biopsy. Samples were collected at 5 time points (0, 3, 6, 9, and 12 months after onset of the study) during 9 months of treatment and 3 months of follow-up, and serum markers were determined as described in Methods. HA, hyaluronic acid; LN, laminin; C-IV, collagen type IV; PC-III, procollagen type III. Clinical Gastroenterology and Hepatology 2005 3, 819-828DOI: (10.1016/S1542-3565(05)00404-0) Copyright © 2005 American Gastroenterological Association Terms and Conditions