桃红化浊汤联合恩替卡韦治疗慢性乙型肝炎肝硬化(湿热蕴结证)临床疗效及安全性

Clinical efficacy and safety of Taohong Huazhuo Decoction combined with entecavir on chronic hepatitis B cirrhosis(damp-heat accumulation syndrome)

目的探讨桃红化浊汤联合恩替卡韦治疗慢性乙型肝炎(chronic hepatitis B,CHB)肝硬化(湿热蕴结证)的临床疗效及安全性。方法前瞻性收集2016年6月至2019年9月西安市中医医院收治的120例CHB肝硬化患者为研究对象,采用随机数字表法将患者分为观察组(60例)和对照组(60例)。对照组采用恩替卡韦治疗,观察组采用桃红化浊汤联合恩替卡韦治疗,比较两组患者治疗前和治疗6个月后单项症状积分、肝功能[包括丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)和总胆红素(total bilirubin,TBil)]、肝纤维化指标[包括透明质酸(hyaluronic acid,HA)、Ⅲ型前胶原氨基末端肽(procollagen typeⅢ,PCⅢ)、层粘连蛋白(laminin,LN)、Ⅳ型胶原(Ⅳcollagen,Ⅳ-C)、肝脏硬度值(liver stiffness measurement,LSM)和FIB-4指数]及HBV DNA载量。比较两组患者的治疗总有效率和不良反应发生率。结果治疗后,两组患者的症状积分均显著低于治疗前,包括双目或皮肤发黄[观察组:(2.22±0.41)分vs(5.22±2.36)分;对照组:(3.41±1.24)分vs(5.17±2.37)分]、恶心呕吐[观察组:(3.47±0.99)分vs(5.63±2.00)分;对照组:(4.48±1.47)分vs(6.30±2.04)分]、食欲不振[观察组:(2.63±0.76)分vs(6.80±1.54)分;对照组:(3.85±1.15)分vs(6.90±1.54)分]、脘腹撑急[观察组:(2.25±0.60)分vs(4.87±1.92)分;对照组:(3.60±1.01)分vs(4.98±1.40)分]及腹胀[观察组:(2.18±0.83)分vs(5.30±1.06)分;对照组:(3.45±1.06)分vs(5.17±1.56)分],且观察组上述症状积分均显著低于对照组,差异均有统计学意义(P均<0.001)。治疗后,两组患者肝功能指标水平均显著低于治疗前,包括血清ALT[观察组:(23.44±4.03)U/L vs(59.07±8.82)U/L;对照组:(39.42±5.09)U/L vs(56.92±7.77)U/L]、AST[观察组:(22.07±4.23)U/L vs(46.18±6.53)U/L;对照组:(35.97±4.03)U/L vs(47.58±7.52)U/L]和TBil[观察组:(9.20±2.27)μmol/L vs(23.98±3.91)μmol/L;对照组:(14.32±4.11)μmol/L vs(24.66±3.55)μmol/L],且观察组治疗后上述指标显著低于对照组,差异均有统计学意义(P均<0.001)。治疗后,两组患者肝纤维化指标水平均显著低于治疗前,包括血清PCⅢ[观察组:(123.35±26.10)μg/L vs(172.83±44.03)μg/L;对照组:(143.90±36.34)μg/L vs(177.71±33.50)μg/L]、Ⅳ-C[观察组:(120.54±35.12)μg/L vs(215.60±56.18)μg/L;对照组:(144.20±42.76)μg/L vs(200.52±67.23)μg/L]、HA[观察组:(122.82±30.89)μg/L vs(259.41±64.13)μg/L;对照组:(135.42±27.15)μg/L vs(257.83±54.35)μg/L]、LN[观察组:(142.97±31.44)μg/L vs(223.37±46.05)μg/L;对照组:(168.92±32.95)μg/L vs(209.53±45.07)μg/L]、LSM[观察组:(16.28±2.55)kPa vs(21.16±2.89)kPa;对照组:(18.61±2.04)kPa vs(21.15±4.31)kPa]及FIB-4指数(观察组:1.29±0.38 vs 2.23±0.55;对照组:1.57±0.36 vs 2.36±0.29),且观察组患者上述指标均显著低于对照组,差异均有统计学意义(P均<0.05)。治疗后,两组患者HBV DNA载量均显著低于治疗前[观察组:(3.07±1.48)lg IU/ml vs(7.16±1.36)lg IU/ml;对照组:(3.11±1.56)lg IU/ml vs(7.30±1.28)lg IU/ml;t=24.001、22.856,P均<0.001],观察组和对照组间差异无统计学意义(t=0.134,P=0.894);观察组和对照组HBV DNA低于检测下限率分别为88.33%(53/60)、86.67%(52/60),差异无统计学意义(χ^(2)=0.076,P=0.783)。治疗后,观察组患者总有效率为91.67%(55/60),显著高于对照组的76.67%(46/60),差异有统计学意义(χ^(2)=5.065,P=0.024)。治疗期间观察组和对照组不良反应发生率分别为6.67%(4/60)、10.00%(6/60),差异无统计学意义(χ^(2)=0.436,P=0.509)。结论桃红化浊汤联合恩替卡韦治疗CHB肝硬化(湿热蕴结证)可提高临床疗效,改善患者临床症状和肝功能,抑制肝纤维化,安全可靠。

Objective To investigate the clinical efficacy and safety of Taohong Huazhuo Decoction combined with entecavir on chronic hepatitis B(CHB)cirrhosis(damp-heat accumulation syndrome).Methods A total of 120 patients with CHB cirrhosis who were admitted to Xi’an Hospital of Traditional Chinese Medicine from June 2016 to September 2019 were collected prospectively as the research subjects.The patients were divided into observation group(60 cases)and control group(60 cases)according to random number table method.Patients in control group were treated with entecavir,while patients in observation group were treated with Taohong Huazhuo Decoction combined with entecavir.The scores of single symptoms,liver function indexes[including alanine aminotransferase(ALT),aspartate aminotransferase(AST)and total bilirubin(TBil)],liver fibrosis indexes[including hyaluronic acid(HA),procollagen typeⅢ(PCⅢ),laminin(LN),Ⅳcollagen(Ⅳ-C),liver stiffness measurement(LSM)and FIB-4 index]and HBV DNA load of patients in both groups before treatment and 6 months after treatment were compared.The total response rate and incidence of adverse reactions were also compared.Results After treatment,the scores of single symptoms of patients in both groups were significantly lower than those before treatment,including binocular or skin yellowing[observation group:(2.22±0.41)points vs(5.22±2.36)points;control group:(3.41±1.24)points vs(5.17±2.37)points],nausea and vomiting[observation group:(3.47±0.99)points vs(5.63±2.00)points;control group:(4.48±1.47)points vs(6.30±2.04)points],inappetence[observation group:(2.63±0.76)points vs(6.80±1.54)points;control group:(3.85±1.15)points vs(6.90±1.54)points],stomach distension[observation group:(2.25±0.60)points vs(4.87±1.92)points;control group:(3.60±1.01)points vs(4.98±1.4)points]and abdominal distension[observation group:(2.18±0.83)points vs(5.30±1.06)points;control group:(3.45±1.06)points vs(5.17±1.56)points],and the above symptom scores of patients in observation group were significantly lower than those of control group,the differences were statistically significant(all P<0.001).After treatment,the serum levels of liver function indexes of patients in both groups were significantly lower than those before treatment,including ALT[observation group:(23.44±4.03)U/L vs(59.07±8.82)U/L;control group:(39.42±5.09)U/L vs(56.92±7.77)U/L],AST[observation group:(22.07±4.23)U/L vs(46.18±6.53)U/L;control group:(35.97±4.03)U/L vs(47.58±7.52)U/L]and TBil[observation group:(9.20±2.27)μmol/L vs(23.98±3.91)μmol/L;control group:(14.32±4.11)μmol/L vs(24.66±3.55)μmol/L],and the above indexes of patients in observation group were significantly lower than those of control group,the differences were statistically significant(all P<0.001).After treatment,the serum levels of liver fibrosis indexes of patients in both groups were significantly lower than those before treatment,including PCⅢ[observation group:(123.35±26.10)μg/L vs(172.83±44.03)μg/L;control group:(143.90±36.34)μg/L vs(177.71±33.50)μg/L],Ⅳ-C[observation group:(120.54±35.12)μg/L vs(215.60±56.18)μg/L;control group:(144.20±42.76)μg/L vs(200.52±67.23)μg/L],HA[observation group:(122.82±30.89)μg/L vs(259.41±64.13)μg/L;control group:(135.42±27.15)μg/L vs(257.83±54.35)μg/L],LN[observation group:(142.97±31.44)μg/L vs(223.37±46.05)μg/L;control group:(168.92±32.95)μg/L vs(209.53±45.07)μg/L],LSM[observation group:(16.28±2.55)kPa vs(21.16±2.89)kPa;control group:(18.61±2.049)kPa vs(21.15±4.31)kPa]and FIB-4 index(observation group:1.29±0.38 vs 2.23±0.55;control group:1.57±0.36 vs 2.36±0.29),and the above indexes of patients in observation group were significantly lower than those of control group,the differences were statistically significant(all P<0.05).After treatment,the HBV DNA load[observation group:(3.07±1.48)lg IU/ml vs(7.16±1.36)lg IU/ml;control group:(3.11±1.56)lg IU/ml vs(7.30±1.28)lg IU/ml]of patients in both groups were significantly lower than those before treatment(t=24.001,22.856;all P<0.001)and there was no significant difference between observation group and control group(t=0.134,P=0.894).After treatment,the rates of HBV DNA load lower than the low detection limit of patients in observation group and control group were 88.33%(53/60)and 86.67%(52/60),respectively,the difference was not statistically significant(χ^(2)=0.076,P=0.783).The total response rate of patients in observation group was 91.67%(55/60),which was significantly higher than that of control group[76.67%(46/60)],the difference was statistically significant(χ^(2)=5.065,P=0.024).The incidence of adverse reactions of patients in observation group and control group were 6.67%(4/60)and 10.00%(6/60),respectively,the difference was not statistically significant(χ^(2)=0.436,P=0.509).Conclusions Taohong Huazhuo Decoction combined with entecavir can improve the clinical efficacy,clinical symptoms and the liver function of CHB cirrhosis,and can also inhibit liver fibrosis,which is safe and reliable.