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-gamma) treatment in patients chronically infected with hepatitis B virus.
Methods: A total of 42 patients, 30 treated with IFN-gamma and 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-gamma treatment 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-gamma-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-gamma-treated patients had stable serum liver function and liver fibrosis indices without any further anti-viral or anti-fibrotic treatment. Improved inflammatory and fibrotic scores were found after nine months of IFN-gamma treatment according to the modified Chevallier scoring system (inflammation: 11.8+/-6.5 at the beginning of IFN-gamma treatment 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-gamma treatment 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-gamma treatment regimens should be assessed in further clinical trials.