中医辨证施治乙型肝炎病毒-慢加急性肝衰竭的思考

Consideration of treatment of hepatitis B virus-acute chronic liver failure with syndrome differentiation in traditional Chinese medicine

目的分析乙型肝炎病毒-慢加急性肝衰竭(HBV-ACLF)的中医证候规律,探讨中医证候实质和中西医结合治疗HBV-ACLF的方案.方法回顾性分析天津市第二人民医院收治的64例HBV-ACLF患者的病例资料,收集入院时患者的中医证候信息,包括症状评分和舌脉积分,采用聚类分析归纳疾病证候特点,评价不同证型的疗效,比较各证型间丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBIL)、白蛋白(ALB)、胆碱酯酶(ChE)、凝血酶原时间(PT)、总胆汁酸(TBA)、凝血酶原活动度(PTA)、纤维蛋白原(FIB)、甲胎蛋白(AFP)等反映肝脏损伤、合成及再生能力指标的差异,分析HBV-ACLF各中医证型的实质.结果64例HBV-ACLF患者的证候、舌质、舌苔、脉象等47项指标信息主要聚类为热毒炽盛证、肝脾血瘀证、肝肾阴虚证、肝郁脾虚证、湿热蕴结证5个证型,所占比例分别为10.94%、10.94%、12.50%、23.43%、42.19%.HBV-ACLF早期患者多为肝郁脾虚证(10例)和湿热蕴结证(12例);HBV-ACLF中期患者中,热毒炽盛证(5例比0例)和肝肾阴虚证(3例比1例)患者较早期患者增多;HBV-ACLF晚期患者中,肝肾阴虚证(4例比3例、1例)和肝脾血瘀证(5例比1例、1例)患者较早期和中期患者增多;各期之间比较差异均有统计学意义(均P<0.05);肝郁脾虚证、湿热蕴结证患者近期疗效明显优于肝脾血瘀证、肝肾阴虚证和热毒炽盛证(治愈为6例、4例比0例、0例、1例,显效为3例、8例比1例、1例、0例,有效为2例、5例比2例、2例、0例,均P<0.05).TBIL、TBA在热毒炽盛证患者中表达最高〔TBIL:(295.09±75.30)μmol/L,TBA:(253.66±44.70)U/L,均P>0.05〕,其次依次为肝郁脾虚证、湿热蕴结证、肝肾阴虚证、肝脾血瘀证,但各证型之间比较差异均无统计学意义;ALT、AST在热毒炽盛证患者中表达最高,在肝脾血瘀证患者中的表达最低;2个证型间的AST比较差异有统计学意义〔U/L:301.20(105.80,638.60)比73.7(65.90,123.30),P<0.05〕.肝脏合成能力方面,肝肾阴虚证患者的凝血相关指标最差,湿热蕴结证最佳,且湿热蕴结证、热毒炽盛证、肝郁脾虚证、肝脾血瘀证、肝肾阴虚证患者的FIB表达比较差异均有统计学意义〔分别为(1.37±0.48)、(1.23±0.51)、(1.28±0.49)、(1.21±0.36)、(0.70±0.42)g/L,均P<0.05〕;肝郁脾虚证和湿热蕴结证患者的ALB、ChE均较高,而肝脾血瘀证和肝肾阴虚证患者的ALB均明显低于湿热蕴结证患者(g/L:25.71±3.52、27.55±3.08比30.88±4.73,均P<0.05).肝脏再生能力方面,湿热蕴结证患者的AFP最高,其次为肝郁脾虚证,肝脾血瘀证最低〔分别为65.64(28.81,171.10)、39.76(10.10,341.00)、4.65(2.27,10.65)ng/L,均P<0.05〕.结论肝郁脾虚证、湿热蕴结证、热毒炽盛证、肝肾阴虚证、肝脾血瘀证为HBV-ACLF的主要证型,能够反映疾病不同阶段肝脏损伤、合成能力及再生能力方面情况.肝郁脾虚证、湿热蕴结证多处于疾病早期,此阶段时可能中西医结合治疗能取得好的疗效;热毒炽盛证最易发生并发症,需联合生物人工肝治疗控制病情;肝脾血瘀证、肝肾阴虚证多处于疾病晚期,建议尽早考虑肝移植.

Objective To analyze the traditional Chinese medicine(TCM)syndromes regulation of hepatitis B virus-acute chronic liver failure(HBV-ACLF),and explore the essence of TCM syndromes and scheme of treating HBV-ACLF with integrated traditional Chinese and Western medicine.Methods The data of 64 cases of HBV-ACLF admitted to Tianjin Second People's Hospital were analyzed retrospectively.The TCM syndrome information of patients at admission was collected,including symptom and tongue pulse scores,cluster analysis was used to summarize the characteristics of syndrome,and the curative effects were evaluated.The indexes of liver injury,synthesis and regeneration among different syndrome types,including alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),albumin(ALB),cholinesterase(ChE),prothrombin time(PT),total bile acid(TBA),prothrombin activity(PTA),fibrinogen(FIB),alpha fetoprotein(AFP),etc were compared and the essence of HBV-ACLF syndromes was analyzed.Results The 47 index information of 64 patients with HVB-ACLF,such as clinical symptoms,tongue texture,tongue coating and pulse signs,etc.were clustered into five main groups,which were heat and toxin excessive syndrome,liver-spleen blood stasis syndrome,liver and kidney Yin deficiency syndrome,liver-stagnation and spleen deficiency syndrome and damp-heat stagnation syndrome,and the proportion was 10.94%,10.94%,12.50%,23.44%and 42.19%,respectively.In the early stage,the liver-stagnation and spleen deficiency syndrome(10 cases)and damp-heat stagnation syndrome(12 cases)were the most common;in the mid-term,the heat and toxin excessive syndrome(case:5 vs.0)and liver and kidney Yin deficiency syndrome(case:3 vs.1)gradually increased compared with those in early stage.In the late stage,the manifestations of liver and kidney Yin deficiency syndrome(case:4 vs.3,1)and liver-spleen blood stasis syndrome(case:5 vs.1,1)were more than those in early stage and mid-term.The difference was statistically significant(P<0.05).The short-term efficacies of patients with liver-stagnation and spleen deficiency syndrome and damp-heat stagnation syndrome were better than those with liver-spleen blood stasis syndrome,liver-kidney Yin deficiency syndrome and heat and toxinexcessive syndrome[cure(case):6,4 vs.0,0,1,markedly effective(case):3,8 vs.1,1,0,effective(case):2,5 vs.2,2,0,all P<0.05].The expression levels of TBIL and TBA were the highest in heat and toxin excessive syndrome[TBIL:(295.09±75.30)μmol/L,TBA:(253.66±44.70)U/L,P>0.05],followed by liver-stagnation and spleen deficiency syndrome,damp-heat stagnation syndrome,liver and kidney Yin deficiency syndrome and liver-spleen blood stasis syndrome.But there was no significant difference among different syndromes.The expression levels of ALT and AST were the highest in heat and toxin excessive syndrome,and the lowest in liver-spleen blood stasis syndrome,with statistically significant difference in AST[U/L:301.20(105.80,638.60)vs.73.70(65.90,123.30),P<0.05].In terms of liver synthesis,the patients with liver and kidney Yin deficiency syndrome had the worst coagulation related indexes,which was the best in the patients with damp-heat stagnation syndrome.There were significant differences in FIB expression among the patients with damp-heat stagnation syndrome,heat and toxin excessive syndrome,liver-stagnation and spleen deficiency syndrome,liver-spleen blood stasis syndrome,and liver and kidney Yin deficiency syndrome[(1.37±0.48),(1.23±0.51),(1.28±0.49),(1.21±0.36)and(0.70±0.42)g/L,all P<0.05].The expression of ALB and ChE in liver-stagnation and spleen deficiency syndrome and damp-heat stagnation syndrome were higher,while the ALB of liver-spleen blood stasis syndrome and liver and kidney Yin deficiency syndrome were significantly lower than that of damp-heat stagnation syndrome(g/L:25.71±3.52,27.55±3.08 vs.30.88±4.73,P<0.05).In the aspect of liver regeneration,the AFP of patients with damp-heat stagnation syndrome was the highest,followed by liver-stagnation and spleen deficiency syndrome,and liver-spleen blood stasis syndrome was the lowest[65.64(28.81,171.10),39.76(10.10,341.00)and 4.65(2.27,10.65)ng/L,all P<0.05].Conclusions Liverstagnation and spleen deficiency syndrome,damp-heat stagnation syndrome,heat and toxin excessive syndrome,liver and kidney Yin deficiency syndrome and liver-spleen blood stasis syndrome are the main syndromes of HBV-ACLF,which can reflect the liver injury,synthesis and regeneration in different stages.Liver-stagnation and spleen deficiency syndrome and damp-heat stagnation syndrome are mostly in the early stage.At this stage,the integrated traditional Chinese and Western medicine may achieve good effect.The heat and toxin excessive syndrome is the most likely to have complications,which needs to be controlled by biological artificial liver therapy;the liver-spleen blood stasis syndrome and liver and kidney Yin deficiency syndrome are mostly in the late stage.It is suggested that liver transplantation be considered as soon as possible.