Published online Feb 15, 2001. doi: 10.3748/wjg.v7.i1.42
Revised: October 12, 2000
Accepted: October 20, 2000
Published online: February 15, 2001
AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-γ) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibrosis.
METHODS: Hepatic fibrosis was successfully induced in 150 and 196 rats by subcutaneous injection of carbon tetrachloride (CCla4) and intraperitoneal injection of dimethylnitrosamine (DMN), respectively. Each of the two model groups was divided into: ① fibrotic model group; ② colchicine treatment group (0.1 mg/kg/day, gastrogavage for 8 weeks); ③ high-dose IFN-γ group (15 MU/kg per day, i.m. for 8 weeks); ④ medium-dose IFN-γ group (5 MU/kg daily, i.m. for 8 weeks); and ⑤ low-dose IFN-γ group (1.67 MU/kg daily, i.m. for 8 weeks). Another group of 10 rats without any treatment was used as normal controls. At the end of the experiment, semi-quantitative histopathological scores of inflammation and fibrosis, liver α smooth muscle actin (α-SMA) expression level, liver hydroxyl proline content and serum hyaluronic acid levels were compared. And 47 medium chronic hepatitis B viral fibrosis patients were studied. They were given IFN-γ treatment, 100 MU/day i.m. for the first three months and 100 MU qod i.m. for the next six months. Semi-quantitative pathological scores of inflammation and fibrosis and serum hepatic fibrosis indices were compared within the 9 months.
RESULTS: In animal experiment, the pathological fibrosis scores and liver hydroxyl proline content were found to be significantly lower in rats treated with different doses of IFN-γ as compared with rats in fibrotic model group induced by either CCla4 or DMN, in a dose-dependent manner. For CCla4-induced model, pathological fibrosis scores in high, medium and low doses IFN-γ groups were 5.10 ± 2.88, 7.70 ± 3.53 and 8.00 ± 3.30, respectively, but the score was 14.60 ± 7.82 in fibrotic model group. Hydroxyl proline contents were 2.83 ± 1.18, 3.59 ± 1.22 and 4.80 ± 1.62, in the three IFN-γ groups, and 10.01 ± 3.23 in fibrotic model group. The difference was statistically significant (P < 0.01). Similar results were found in DMN-induced model. Pathological fibrosis scores were 6.30 ± 0.48, 8.10 ± 2.72 and 8.30 ± 2.58, in high, medium and low doses IFN-γ groups, and 12.59 ± 3.57 in fibrotic model group. Hydroxyl proline contents were 2.72 ± 0.58, 3.14 ± 0.71 and 3.62 ± 1.02, in the three IFN-γ groups, and 12.79 ± 1.54 in fibrotic model group. The difference was statistically significant (P < 0.01). Serum hepatic fibrosis indices decreased significantly in the 47 patients after IFN-γ treatment (HA: 433.38 ± 373.00 vs 281.57 ± 220.48; LN: 161.22 ± 41.02 vs 146.35 ± 44.67; PC(r): 192.59 ± 89.95 vs 156.98 ± 49.22; C-I: 156.30 ± 44.01 vs 139.14 ± 34.47) and the differences between the four indices were significant (P < 0.05). Thirty-three patients received two liver biopsies, one before and one after IFN-γ treatment. In thirty of 33 patients IFN-γ had better effects according to semi-quantitative pathological scores (8.40 ± 5.83 vs 5.30 ± 4.05, P < 0.05).
CONCLUSION: All the three doses of IFN-γ are effective in treating rat liver fibrosis induced by either CCla4 or DMN, the higher the dose, the better the effect. And IFN-γ is effective for patients with moderate chronic hepatitis B viral fibrosis.