扶正化瘀片联合抗病毒药物治疗乙肝肝硬化失代偿期患者的临床疗效及对其肝脏硬度、肝纤维化的影响

Fuzheng Huayu Tablets Combined with Antiviral Drugs in the Treatment of Decompensated Hepatitis B Cirrhosis:Clinical Efficacy and Influences on Liver Stiffness and Liver Fibrosis

目的观察扶正化瘀片联合抗病毒药物治疗乙肝肝硬化(Liver cirrhosisi,LC)失代偿期患者的临床疗效及对其肝脏硬度、肝纤维化的影响。方法选取2020年5月—2022年5月期间淮安市第四人民医院收治的乙肝LC失代偿期患者共260例,按随机数字表法分为对照组和观察组,每组各130例。对照组给予恩替卡韦分散片治疗,观察组在对照组基础上加服扶正化瘀片,均治疗24周。观察比较两组患者治疗前后中医证候积分[胁痛、胁下痞块、面色晦暗、口干不欲饮、乏力]、肝功能[总胆红素(Total bilirubin,TBil)、谷草转氨酶(Alanine aminotransferase,AST)、谷丙转氨酶(Aspartate aminotransferase,ALT)、白蛋白(Albumin,ALB)]、血清肝纤四项[层黏连蛋白(Laminin,LN)、Ⅲ型前胶原(Procollagen typeⅢ,PCⅢ)、IV型胶原(IV collegen,CIV)、透明质酸(Hyaluronic acid,HA)]、肝脾影像学[脾静脉内径、门静脉内径、脾脏厚度、肝脏瞬时弹性硬度(Liver stiff-ness measurement,LSM)]及Th1/Th2型细胞因子[白细胞介素-4(Interleukin-4,IL-4)、白细胞介素-6(Interleukin-6,IL-6)、白细胞介素-18(Interleukin-18,IL-18)、干扰素-γ(Inferferon-γ,IFN-γ)]指标变化情况,评估抗病毒效果[乙肝病毒脱氧核糖核酸(Hepatitis B virus-deoxyribonucleic acid,HBV-DNA)载量及转阴率、乙肝e抗原(Hepatitis B e antigens,HBeAg)转阴率]及临床疗效。结果治疗后两组患者胁痛、胁下痞块、面色晦暗、口干不欲饮和乏力证候积分均较治疗前降低,差异有统计学意义(P<0.05);且观察组胁痛、胁下痞块、面色晦暗、口干不欲饮和乏力证候积分均明显低于对照组,统计学有显著性差异(P<0.05)。治疗后两组患者肝功能TBil、AST、ALT水平均较治疗前降低,ALB水平均较治疗前升高,差异有统计学意义(P<0.05);且观察组TBil、AST、ALT水平均明显低于对照组,ALB水平明显高于对照组,差异有统计学意义(P<0.05)。治疗后两组患者肝纤四项LN、PCШ、CIV和HA指标水平均较治疗前降低,差异有统计学意义(P<0.05);且观察组患者肝纤四项LN、PCШ、CIV和HA指标水平均明显低于对照组,差异有统计学意义(P<0.05)。治疗后两组患者脾静脉内径、门静脉内径、脾脏厚度和LSM指标均较治疗前降低,差异有统计学意义(P<0.05);且观察组脾静脉内径、门静脉内径、脾脏厚度和LSM指标均明显低于对照组,差异有统计学意义(P<0.05)。治疗后观察组患者IL-4、IL-6水平较治疗前降低,IL-18、IFN-γ水平较治疗前升高,差异有统计学意义(P<0.05);对照组Th1/Th2型细胞因子水平与治疗前比较,差异无统计学意义(P>0.05);且观察组IL-4、IL-6水平明显低于对照组,IL-18、IFN-γ水平明显高于对照组,差异有统计学意义(P<0.05)。治疗后观察组HBV-DNA载量低于对照组。观察组HBV-DNA转阴率59.23%(77/130)和HBeAg转阴率56.15%(73/130)明显高于对照组41.54%(54/130)、38.46%(50/130),差异有统计学意义(P<0.05)。治疗后观察组总有效率93.85%(122/130)明显高于对照组81.54(106/130),差异有统计学意义(P<0.05)。结论扶正化瘀片与抗病毒药物联合治疗能够改善乙肝LC失代偿期患者症状和肝功能,降低肝脏硬度和肝纤维化程度,维持Th1/Th2型细胞因子平衡。

Objective To observe the clinical efficacy of Fuzheng Huayu Tablets combined with antiviral drugs in the treatment of decompensated hepatitis B cirrhosis and analyze the influences of this regimen on liver stiffness and liver fibrosis.Methods A total of 260 cases with decompensated hepatitis B liver cirrhosis treated in the Huai′an No.4 People′s Hospital from May 2020 to May 2022 were selected and assigned into a control group and an observation group according to the random number table method,with 130 cases in each group.The control group was treated with Entecavir dispersible tablets,and the observation group with Fuzheng Huayu Tablets on the basis of the therapy in the control group.The treatment in both groups lasted for 24 weeks.The scores of traditional Chinese medicine(TCM)symptoms(hypochondriac pain,hypochondriac mass,dark complexion,dry mouth with no desire to drink,and fatigue),liver function indicators[total bilirubin(TBil),alanine aminotransferase(ALT),aspartate aminotransferase(AST),and albumin(ALB)],serum levels of laminin(LN),procollagen typeⅢ,(PCⅢ),collagen type IV(CIV),and hyaluronic acid(HA),liver and spleen imaging parameters[splenic vein diameter,portal vein diameter,spleen thickness,and liver stiffness measurement(LSM)],and Th1/Th2 cytokines[interleukin-4(IL-4),interleukin-6(IL-6),interleukin-18(IL-18),and interferon-γ(IFN-γ)]were measured before and after treatment in both groups.The antiviral effect[load and positive-to-negative conversion rate of hepatitis B virus-deoxyribonucleic acid(HBV-DNA)and positive-to-negative conversion rate of hepatitis B e antigen(HBeAg)]and clinical efficacy were evaluated.Results After treatment,the TCM symptom scores of hypochondriac pain,hypochondriac mass,dark complexion,dry mouth with no desire to drink,and fatigue declined compared with those before treatment(P<0.05),and the observation group had lower TCM symptom scores than the control group(P<0.05).The treatment in both groups lowered the levels of TBil,AST,and ALT and elevated the level of ALB(P<0.05),and the changes in the observation group were higher than those in the control group(P<0.05).After treatment,the serum levels of LN,PCⅢ,CIV,and HA,together with splenic vein diameter,portal vein diameter,spleen thickness,and LSM in both groups decreased compared with those before treatment(P<0.05),and the decreases in the observation group were more obvious than those in the control group(P<0.05).The treatment in the observation group lowered the levels of IL-4 and IL-6 and elevated the levels of IL-18 and IFN-γ(P<0.05),while that in the control group did not cause significant changes in the levels of IL-4,IL-6,IL-18,and IFN-γ(P>0.05).Moreover,the observation group had lower IL-4 and IL-6 levels and higher IL-18 and IFN-γlevels than the control group after treatment(P<0.05).After treatment,the HBV-DNA load in the observation group was lower than that in the control group(P<0.05).The positive-to-negative conversion rates of HBV-DNA(59.23%,77/130)and HBeAg(56.15%,73/130)in the observation group were higher than those[41.54%(54/130)and 38.46%(50/130)]in the control group(P<0.05).The total response rate in the observation group was 93.85%(122/130),which was higher than that(81.54%,106/130)in the control group(P<0.05).Conclusion Fuzheng Huayu Tablets combined with antiviral drugs can alleviate the symptoms,improve the liver function,reduce liver stiffness and liver fibrosis,and maintain the balance of Th1/Th2 cytokines in the patients with decompensated hepatitis B cirrhosis,demonstrating definite efficacy.