AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibr...AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) 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 (CCl4) 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-gamma group (15 MU/kg per day, i.m. for 8 weeks); (4) medium-dose IFN-gamma group (5 MU/kg daily, i.m. for 8 weeks); and (5) Y low-dose IFN-gamma 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 alpha smooth muscle actin (alpha-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-gamma 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-gamma as compared with rats in fibrotic model group induced by either CCl4 or DMN, in a dose-dependent manner. For CCl4-induced model, pathological fibrosis scores in high, medium and low doses IFN-gamma 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-gamma 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-gamma groups, and 12.60 +/- 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-gamma 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-gamma treatment (HA: 433.38 +/- 373.00 vs 281.57 +/- 220.48; LN: 161.22 +/- 41.02 vs 146 +/- 35 +/- 44. 67; PC III: 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-gamma treatment. In thirty of 33 patients IFN-gamma 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-gamma are effective in treating rat liver fibrosis induced by either CCl4 or DMN, the higher the dose, the better the effect. And IFN-gamma is effective for patients with moderate chronic hepatitis B viral fibrosis.展开更多
目的:观察薄芝糖肽和胸腺五肽分别联合重组人干扰素α2b治疗慢性乙型肝炎的疗效及安全性。方法:选择2014年1月-2015年1月我院90例慢性乙型肝炎患者,随机分为A、B、C组,各30例。A组患者给予注射用重组人干扰素α2b(假单胞菌)500万IU皮下...目的:观察薄芝糖肽和胸腺五肽分别联合重组人干扰素α2b治疗慢性乙型肝炎的疗效及安全性。方法:选择2014年1月-2015年1月我院90例慢性乙型肝炎患者,随机分为A、B、C组,各30例。A组患者给予注射用重组人干扰素α2b(假单胞菌)500万IU皮下注射,qod;B组患者在A组基础上加用薄芝糖肽注射液4 m L加入5%葡萄糖注射液250 m L中,ivgtt,qd;C组患者在A组基础上加用注射用胸腺五肽2 mg加入5%葡萄糖注射液250 m L中,ivgtt,qd。3组患者均治疗24周。比较3组患者治疗4、8、12、24周丙氨酸转氨酶(ALT)复常率、HBeAg阴转率、HBeAg/抗HBeAg血清转换率(以下简称"HBeAg转换率")、HBV-DNA阴转率、乙肝表面抗原(HBsAg)和HBV-DNA下降量,治疗24周时的HBsAg阴转率,并记录不良反应的发生情况。结果:治疗4、8、12周,3组患者ALT复常率、HBeAg阴转率、HBeAg转换率、HBsAg下降量比较,差异均无统计学意义(P>0.05)。治疗4周,B组和C组患者HBV-DNA转阴率显著高于A组,C组患者HBV-DNA下降量显著大于A组和B组,差异有统计学意义(P<0.05)。治疗8、12周,B组和C组患者HBV-DNA阴转率和HBV-DNA下降量显著高于A组,差异有统计学意义(P<0.05),但B组与C组间比较,差异无统计学意义(P>0.05)。治疗24周,3组患者ALT复常率、HBeAg转换率、HBsAg下降量及HBsAg阴转率比较,差异均无统计学意义(P>0.05);B组和C组患者HBeAg阴转率、HBV-DNA阴转率和HBV-DNA下降量显著高于A组,差异有统计学意义(P<0.05),但B组与C组间比较,差异无统计学意义(P>0.05)。3组患者不良反应发生率比较,差异无统计学意义(P>0.05)。结论:薄芝糖肽和胸腺五肽分别联合重组人干扰素α2b对慢性乙型肝炎具有较好的抑制病毒增殖作用,且在ALT复常率、HBeAg转换率、HBsAg下降量及HBsAg阴转率方面效果相当。展开更多
OBJECTIVE: To investigate the compositions of Th1/Th2/Th3 cells in chronic hepatitis B virus (HBV)-infected individuals by determining the expression of interleukin-4 (IL-4), inetrferon-gamma (IFN-gamma), and transfor...OBJECTIVE: To investigate the compositions of Th1/Th2/Th3 cells in chronic hepatitis B virus (HBV)-infected individuals by determining the expression of interleukin-4 (IL-4), inetrferon-gamma (IFN-gamma), and transform growth factor-beta (TGF-beta) in single CD4(+) T cells isolated from peripheral blood mononuclear cells (PBMCs) and the role of polarized Th cell populations in chronic HBV-infection was discussed. METHODS: PBMCs from chronically infected HBV individuals were isolated, stimulated by PMA/Ionomycin/Monensin, and IL-4, IFN-gamma and TGF-beta production by CD4(+) T cells was determined by using fluorescence activated cell sorter (FACS) analysis. RESULTS: The percentage of IFN-gamma-producing T cells, IL-4-producing T cells and TGF-beta-producing T cells ranged from 2.3% - 18.6%, 1.1% - 8.7% and 0.7% - 7.1% respectively in CD4(+) T cells from non-infected individuals. Most of CD4(+) T cells from PBMCs in chronically infected HBV individuals were Th0 cells. The proportion of Th1 cells increased significantly with hepatic inflammatory activity, and in the active period of chronic hepatitis B infection were higher than those in the non-active period (P 0.05), but were higher than that from controls (P展开更多
文摘AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) 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 (CCl4) 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-gamma group (15 MU/kg per day, i.m. for 8 weeks); (4) medium-dose IFN-gamma group (5 MU/kg daily, i.m. for 8 weeks); and (5) Y low-dose IFN-gamma 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 alpha smooth muscle actin (alpha-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-gamma 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-gamma as compared with rats in fibrotic model group induced by either CCl4 or DMN, in a dose-dependent manner. For CCl4-induced model, pathological fibrosis scores in high, medium and low doses IFN-gamma 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-gamma 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-gamma groups, and 12.60 +/- 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-gamma 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-gamma treatment (HA: 433.38 +/- 373.00 vs 281.57 +/- 220.48; LN: 161.22 +/- 41.02 vs 146 +/- 35 +/- 44. 67; PC III: 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-gamma treatment. In thirty of 33 patients IFN-gamma 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-gamma are effective in treating rat liver fibrosis induced by either CCl4 or DMN, the higher the dose, the better the effect. And IFN-gamma is effective for patients with moderate chronic hepatitis B viral fibrosis.
文摘目的:观察薄芝糖肽和胸腺五肽分别联合重组人干扰素α2b治疗慢性乙型肝炎的疗效及安全性。方法:选择2014年1月-2015年1月我院90例慢性乙型肝炎患者,随机分为A、B、C组,各30例。A组患者给予注射用重组人干扰素α2b(假单胞菌)500万IU皮下注射,qod;B组患者在A组基础上加用薄芝糖肽注射液4 m L加入5%葡萄糖注射液250 m L中,ivgtt,qd;C组患者在A组基础上加用注射用胸腺五肽2 mg加入5%葡萄糖注射液250 m L中,ivgtt,qd。3组患者均治疗24周。比较3组患者治疗4、8、12、24周丙氨酸转氨酶(ALT)复常率、HBeAg阴转率、HBeAg/抗HBeAg血清转换率(以下简称"HBeAg转换率")、HBV-DNA阴转率、乙肝表面抗原(HBsAg)和HBV-DNA下降量,治疗24周时的HBsAg阴转率,并记录不良反应的发生情况。结果:治疗4、8、12周,3组患者ALT复常率、HBeAg阴转率、HBeAg转换率、HBsAg下降量比较,差异均无统计学意义(P>0.05)。治疗4周,B组和C组患者HBV-DNA转阴率显著高于A组,C组患者HBV-DNA下降量显著大于A组和B组,差异有统计学意义(P<0.05)。治疗8、12周,B组和C组患者HBV-DNA阴转率和HBV-DNA下降量显著高于A组,差异有统计学意义(P<0.05),但B组与C组间比较,差异无统计学意义(P>0.05)。治疗24周,3组患者ALT复常率、HBeAg转换率、HBsAg下降量及HBsAg阴转率比较,差异均无统计学意义(P>0.05);B组和C组患者HBeAg阴转率、HBV-DNA阴转率和HBV-DNA下降量显著高于A组,差异有统计学意义(P<0.05),但B组与C组间比较,差异无统计学意义(P>0.05)。3组患者不良反应发生率比较,差异无统计学意义(P>0.05)。结论:薄芝糖肽和胸腺五肽分别联合重组人干扰素α2b对慢性乙型肝炎具有较好的抑制病毒增殖作用,且在ALT复常率、HBeAg转换率、HBsAg下降量及HBsAg阴转率方面效果相当。
文摘OBJECTIVE: To investigate the compositions of Th1/Th2/Th3 cells in chronic hepatitis B virus (HBV)-infected individuals by determining the expression of interleukin-4 (IL-4), inetrferon-gamma (IFN-gamma), and transform growth factor-beta (TGF-beta) in single CD4(+) T cells isolated from peripheral blood mononuclear cells (PBMCs) and the role of polarized Th cell populations in chronic HBV-infection was discussed. METHODS: PBMCs from chronically infected HBV individuals were isolated, stimulated by PMA/Ionomycin/Monensin, and IL-4, IFN-gamma and TGF-beta production by CD4(+) T cells was determined by using fluorescence activated cell sorter (FACS) analysis. RESULTS: The percentage of IFN-gamma-producing T cells, IL-4-producing T cells and TGF-beta-producing T cells ranged from 2.3% - 18.6%, 1.1% - 8.7% and 0.7% - 7.1% respectively in CD4(+) T cells from non-infected individuals. Most of CD4(+) T cells from PBMCs in chronically infected HBV individuals were Th0 cells. The proportion of Th1 cells increased significantly with hepatic inflammatory activity, and in the active period of chronic hepatitis B infection were higher than those in the non-active period (P 0.05), but were higher than that from controls (P
