Hepatic fibrosis in patients with chronic hepatitis B virus infection can be partially reversed by IFN-γ

Abstract

Background. Hepatic fibrosis due to chronic hepatitis B virus (HBV) infection has an enormous socio-economic impact. Besides strategies aiming at virus elimination, prevention or reversal of liver fibrosis is amenible. Given the antifibrotic activity of IFN-γ, a randomized open-labeled multicenter trial was initiated to test IFN-γ in HBV infection. Methods. HBs-antigen positive patients with biopsy proven hepatic fibrosis (n=99, stages 2–4 according to Scheuer criterion) were treated with diammone glycyrrhizinate and potassium magnesium aspartate.Treatment with 50g IFN-γ i.m. on a daily basis for three months and on alternate days the subsequent six months was performed in 66 randomly assigned patients. Efficacy was evaluated by liver biopsy and serologic markers. Results. 54 patients in the IFN-γ group and 29 patients in the control group completed the study protocol. The hepatic fibrosis score was significantly reduced in 63 percent of IFN-γ treated patients compared to 24.1 percent in the control group as assessed by a semiquantitative scoring system evaluating both liver architecture and fibrotic deposits. Mean values for total fibrosis score decreased from 13.8±5.8 to 10.1±5.1 in the IFN-γ group, whereas they were unchanged in controls (13.2±6.8 versus 12.6±4.8 after 9 months). The Scheuer fibrosis scoring system revealed 12 out of 54 patients improved 1 stage(s) in the IFN-γ compared to 1/29 in the control group. Antifibrotic activity may be attributed to decreased TGF-β signaling via phospho-Smad2 and reduced number of activated, α smooth muscle actin positive hepatic stellate cells. Conclusions. Prolonged IFN-γ treatment over 9 months significantly improves the fibrosis score in patients with chronic HBV infection most likely by antagonizing profibrogenic TGF-β effects.