【摘要】 目的研究HBe Ag阳性慢性乙型肝炎(CHB)患者应用恩替卡韦(ETV)联合胸腺肽治疗的临床疗效。方法纳入2012年3月-2015年3月于上海市第八人民医院传染病科就诊的HBe Ag阳性CHB患者108例,根据平行、单盲、随机对照原则分为对照组(54例)和观察组(54例)。两组均接受内科综合治疗,对照组单用ETV治疗,观察组应用ETV联合胸腺肽治疗。对比两组肝功能指标、病毒学指标、免疫指标及肝纤维化指标变化。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验。结果治疗48周后,观察组的肝功能指标(Alb/Glo、ALT、AST、TBil)与对照组比较差异均有统计学意义[(1.73±0.57)vs(1.50±0.51)、(42.58±14.32)U/L vs(54.26±18.78)U/L、(35.79±10.33)U/L vs(49.97±17.84)U/L、(18.89±6.02)μmol/L vs(25.24±9.06)μmol/L,t值分别为2.210、3.634、5.055、4.290,P值均<0.05];治疗48周后,观察组的肝纤维化指标(层黏连蛋白、透明质酸、Ⅳ型胶原片段、Ⅲ型前胶原)与对照组比较差异均有统计学意义[(65.34±11.02)ng/ml vs(102.57±16.41)ng/ml、(91.68±11.53)ng/ml vs(151.23±16.71)ng/ml、(81.02±12.64)μg/ml vs(118.47±18.01)μg/ml、(70.44±13.06)μg/ml vs(91.57±17.16)μg/ml,t值分别为13.840、21.555、12.507、7.200,P值均<0.001];治疗12、24及48周时,观察组HBe Ag阴转率分别为29.63%、46.30%、57.41%,显著高于对照组的12.96%、22.22%、25.93%(χ2值分别为4.475、6.948、11.009,P值均<0.05);治疗48周后观察组的血清IL-4为(2.69±1.23)pg/ml,显著低于对照组的(4.38±1.44)pg/ml(t=6.558,P<0.001),IFNγ水平为(1.82±0.89)pg/ml,显著高于对照组的(1.12±0.56)pg/ml(t=4.812,P<0.001);观察组的不良反应率为3.70%,与对照组的1.85%比较,差异无统计学意义(χ2=0.343,P=0.558)。结论 HBe Ag阳性CHB患者应用恩替卡韦联合胸腺肽治疗能够促进肝功能康复,调节免疫功能,提高HBe Ag阴转率并抑制肝纤维化进程。更多还原

【Abstract】 Objective To investigate the clinical effect of entecavir( ETV) combined with thymosin in the treatment of HBe Ag- positive chronic hepatitis B( CHB) patients. Methods A total of 108 HBe Ag- positive CHB patients who were treated in Department of Infectious Diseases in our hospital from March 2012 to March 2015 were enrolled,and according to the parallel,single- blind,randomized controlled principles,the patients were divided into control group( 54 patients) and observation group( 54 patients). The patients in both groups were given comprehensive medical treatment; the patients in the control group were treated with ETV alone,and those in the observation group were treated with ETV combined with thymosin. The changes in liver function parameters,virological parameters,immune indices,and liver fibrosis indicators were compared between the two group. The t- test was used for comparison of continuous data between groups,and the chi- square test was used for comparison of categorical data between groups. Results After 48 weeks of treatment,there were significant differences between the observation group and the control group in the liver function parameters albumin / globulin ratio( 1. 73 ± 0. 57 vs 1. 50 ± 0. 51,t =2. 210,P < 0. 05),alanine aminotransferase( 42. 58 ± 14. 32 U / L vs 54. 26 ± 18. 78 U / L,t = 3. 634,P < 0. 05),aspartate aminotransferase( 35. 79 ± 10. 33 U / L vs 49. 97 ± 17. 84 U / L,t = 5. 055,P < 0. 05),and total bilirubin( 18. 89 ± 6. 02 μmol / L vs 25. 24 ± 9. 06μmol /L,t = 4. 290,P < 0. 05). After 48 weeks of treatment,there were significant differences between the observation group and the control group in the liver fibrosis indicators laminin( 65. 34 ± 11. 02 ng / ml vs 102. 57 ± 16. 41 ng / ml,t = 13. 840,P < 0. 001),hyaluronic acid( 91. 68 ± 11. 53 ng / ml vs 151. 23 ± 16. 71 ng / ml,t = 21. 555,P < 0. 001),type IV collagen( 81. 02 ± 12. 64 μg / ml vs 118. 47 ±18. 01 μg / ml,t = 12. 507,P < 0. 001),and procollagen III( 70. 44 ± 13. 06 μg / ml vs 91. 57 ± 17. 16 μg / ml,t = 7. 200,P < 0. 001). At weeks 12,24,and 48 of treatment,the observation group had significantly higher HBe Ag clearance rates than the control group( 29. 63% /46. 30% /57. 41% vs 12. 96% /22. 22% /25. 93%,χ2= 4. 475,6. 948,and 11. 009,all P < 0. 05). After 48 weeks of treatment,compared with the control group,the observation group had a significantly lower serum level of interleukin- 4( 2. 69 ± 1. 23 pg / ml vs 4. 38 ±1. 44 pg / ml,t = 6. 558,P < 0. 001) and a significantly higher level of interferonγ( 1. 82 ± 0. 89 pg / ml vs 1. 12 ± 0. 56 pg / ml,t = 4. 812,P < 0. 001). There was no significant difference in the incidence rate of adverse events between the observation group and the control group( 3. 70% vs 1. 85%,χ2= 0. 343,P = 0. 558). Conclusion In HBeA g- positive CHB patients,ETV combined with thymosin can promote the recovery of liver function,regulate immune function,improve HBeA g clearance rate,and inhibit the process of liver fibrosis.更多还原