Long-term antifibrotic action of interferon-γ treatment in patients with chronic hepatitis B virus infection

BACKGROUND:The first priority in treating fibrosis is to eliminate the causes that result in liver injury,e.g.,hepatitis B and C virus.However,in many liver diseases the cause is either unknown or untreatable.The present study was designed to investigate the long-term antifibrotic effect of interferon-gamma(IFN-γ)treatment in patients chronically infected with hepatitis B virus. METHODS:A total of 42 patients,30 treated with IFN-γand 12 controls,were enrolled from an original clinical trial(Clin Gastroenterol Hepatol 2005;3:819.).Three serial liver biopsies that were obtained at the initiation and end of IFN-γtreatment as well as 4 to 6 years after treatment discontinuation were assessed according to the modified Chevallier scoring system. RESULTS:Twenty-five out of 30 IFN-γ-treated patients were followed up until 4 to 6 years after the treatment was stopped. However,all controls were excluded from follow-up due to death,loss and elevated virus level within 2 years.Twenty-five IFN-γ-treated patients had stable serum liver function and liver fibrosis indices without any further antiviral or anti-fibrotic treatment.Improved inflammatory and fibrotic scores were found after nine months of IFN-γtreatment according to the modified Chevallier scoring system(inflammation:11.8±6.5 at the beginning of IFN-γtreatment vs.9.2±4.1 after 9 months, P<0.05;fibrosis:15.0±7.3 at baseline vs.12.6±6.8 after 9 months, P<0.05).Among them,14 patients accepted a third serial liver biopsy 4 to 6 years after treatment discontinuation,and the fibrotic score was increased(14.2±8.3 vs.11.9±7.6 after 9 months, P<0.05). CONCLUSIONS:Nine-month IFN-γtreatment significantly improves the fibrosis score in patients with chronic HBV infection.The majority of patients demonstrate stable serum biochemical indices and quality of life.However,they do not show a long-term benefit according to histological criteria. Given the limited sample size,long-term IFN-γtreatment regimens should be assessed in further clinical trials.