恩替卡韦联合中药治疗乙型肝炎早期肝硬化的疗效分析

Effect of Entecavir combined with Traditional Chinese Medicine therapy based on syndrome differentiation on early hepatitis B cirrhosisbyWnt/β-catenin pathway

目的:探讨恩替卡韦联合中药方剂辨证治疗乙型肝炎早期肝硬化的临床疗效以及对Wnt/β-catenin通路相关因子的影响。方法:选择2018年6月至2020年10月治疗的慢性乙型肝炎早期肝硬化患者160例,随机分为2组,对照组80例患者接受恩替卡韦抗病毒治疗,治疗组80例患者在对照组的基础上加用中药方剂辨证施治,疗程均为6个月。比较2组患者中医证候积分、西医临床疗效、乙型肝炎病毒学指标[HBV DNA定量、乙型肝炎表面抗原(HBsAg)和乙型肝炎病毒e抗原(HBeAg)]、肝功能指标[丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、血清白蛋白(Alb)、总胆红素(TBil)]、肝纤维化指标[透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原(PC-Ⅲ)、Ⅳ型胶原(Ⅳ-C)]、Wnt/β-catenin通路相关因子[Wnt-1诱导分泌蛋白1(WISP1)、WISP3、β-catenin]和不良反应的发生率。结果:治疗后,治疗组患者中医证候临床疗效和西医临床疗效均优于对照组,总有效率高于对照组(P<0.05)。根据中医证候积分,治疗组患者胁肋不适、恶心呕吐、脘闷、纳呆评分以及中医证候总评分低于对照组(P<0.05)。治疗组患者HBV DNA水平、血清ALT、TBil、HA、LN、PC-Ⅲ、Ⅳ-C以及WISP1、WISP3、β-catenin水平低于对照组,同时Alb水平高于对照组(P<0.05)。2组患者不良反应发生率差异无统计学意义(6.25%vs 7.50%,P>0.05)。结论:中药联合恩替卡韦抗病毒治疗,可有效促进乙型肝炎早期肝硬化患者肝功能恢复,降低肝纤维化指标,疗效确切,且安全性良好,其作用机制可能与抑制Wnt/β-catenin信号通路激活有关。

Objective:To investigate the effect of Entecavir combined with Traditional Chinese Medicine(TCM)therapy based on syndrome differentiationin the treatment of patients withhepatitis B cirrhosisbyWnt/β-catenin pathway.Methods:A total of 160 patients(Child-Pugh A~B grade of liver function)with early cirrhosis of chronic hepatitis B were selected from June 2018 to October 2020 and randomly divided into control group and treatment group.80 patients in the control group were treated with Entecavir anti-HBV therapy,while 80 patients in the treatment group were treated with TCM therapy based on syndrome differentiation combined with Entecavir for 6 months.The therapeutic effect of TCM Syndrome integral,clinical effect of Western medicine,HBV DNA quantity,hepatitis B surface antigen(HBsAg)and hepatitis B virus e antigen(HBeAg),liver function index[Alanine transaminase(ALT),aspartate transaminase(AST),albumin(Alb),total Bilirubin(TBil)],liver fibrosis index[hyaluronic acid(HA),Laminin(LN),type Ⅲ Procollagen(PC-Ⅲ),type Ⅳ Collagen(Ⅳ-C)],Wnt/β-catenin pathway related factors[Wnt induced secreted protein 1(WISP1),WISP3,β-catenin]and incidence of adverse reactions.Results:After treatment,the clinical effects of TCM Syndrome and Western medicine in the treatment group were both better than thatin the control group,and the total effective rates were also both higher than that in the control group(P<0.05).According to the scores of TCM syndromes,the patients in the treatment group were lower than those in the control group(P<0.05).According to laboratory examination,the levels of HBV DNA,ALT,TBil,liver fibrosis(HA,LN,PC-Ⅲ,Ⅳ-C)and Wnt/β-catenin pathway-related factors(WISP1,WISP3,β-catenin)in the treatment group were lower than those in the control group,meanwhile,the level of Alb was higher than that of control group(P<0.05).There was no significant difference in the incidence of drug-related adverse reactions between the two groups(6.25%vs 7.50%)(P<0.05).Conclusion:TCM therapy based on syndrome differentiation combined with anti-virus therapy of Entecavir can effectively promote the recovery of liver function and reduce the index of liver fibrosis in patients with early hepatitis B cirrhosis.The curative effect is definite and the safety is good,the mechanism may be related to the inhibition of activation of Wnt/β-catenin signaling pathway.