Effect of interferon-gamma on hepatic fibrosis in chronic hepatitis B virus infection: a randomized controlled study.
OBJECTIVE
Hepatic fibrosis due to chronic HBV infection has enormous socioeconomic impact. Besides strategies targeting virus elimination, prevention or reversal of liver fibrosis is amenable. Given the antifibrotic activity of interferon-gamma (IFN-gamma), a randomized open-labeled multicenter trial was initiated to test IFN-gamma in HBV infection.


METHODS
HBsAg-positive patients with biopsy proven hepatic fibrosis (n = 99, stages 2-4, Scheuer criterion) were treated with diammone-glycyrrhizinate and potassium-magnesium aspartate. Sixty-six randomly assigned patients were treated with 50 mug IFN-gamma intramuscularly on a daily basis for 3 months and on alternate days the subsequent 6 months. Efficacy was evaluated by liver biopsy and serologic markers.


RESULTS
Fifty-four patients in the IFN-gamma group and 29 patients in the control group completed the study. The hepatic fibrosis score was significantly reduced in 63% of IFN-gamma treated patients compared with 24.1% in the control group by using a semiquantitative scoring system evaluating both liver architecture and fibrotic deposits. Mean values for the total fibrosis score decreased from 13.8 +/- 5.8 to 10.1 +/- 5.1 in the IFN-gamma group (P = .0001), whereas they were unchanged in control subjects (13.2 +/- 6.8 vs 12.6 +/- 4.8, P = .937). The Scheuer system showed 12 out of 54 patients improved >or=1 stage(s) in the IFN-gamma group compared with 1 of 29 in the control group. Antifibrotic activity might be attributed to decreased transforming growth factor-beta signaling via phosphorylated Smad2 and reduced number of activated, alpha-smooth muscle actin positive hepatic stellate cells.


CONCLUSIONS
IFN-gamma treatment for 9 months improves fibrosis scores in patients with chronic HBV infection most likely by antagonizing profibrogenic transforming growth factor-beta effects.
Weng
Hong-Lei
HL
Institute of Infectious Diseases, First Affiliated Hospital, Medical School, Zhejiang University, Hangzhou, China. hongleiweng@zju.edu.cn
Wang
Bao-En
BE
Jia
Ji-Dong
JD
Wu
Wan-Fen
WF
Xian
Jian-Zhong
JZ
Mertens
Peter R
PR
Cai
Wei-Min
WM
Dooley
Steven
S
D000199:Actins / Q000032:analysis; D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001707:Biopsy, Needle; D024061:Collagen Type III / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D019695:Glycyrrhizic Acid / Q000627:therapeutic use; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000627:therapeutic use*; D007797:Laminin / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000737:chemistry; D011195:Potassium Magnesium Aspartate / Q000627:therapeutic use; D011446:Prospective Studies; D012720:Severity of Illness Index; D051899:Smad2 Protein / Q000378:metabolism
D000199:Actins; D000890:Anti-Infective Agents; D024061:Collagen Type III; D024141:Collagen Type IV; D007797:Laminin; D051899:Smad2 Protein; D019695:Glycyrrhizic Acid; D011195:Potassium Magnesium Aspartate; D007371:Interferon-gamma; D006820:Hyaluronic Acid