乙肝肝硬化肠道菌群变化与肝功能Child-Pugh分级、LPS及血氨的相关性

Correlation between intestinal microflora changes in hepatitis B cirrhosis and liver function Child-Pugh classification,LPS,and blood ammonia

目的探讨乙肝肝硬化患者肠道菌群变化与肝功能Child-Pugh分级、内毒素(lipopolysaccharide,LPS)及血氨的相关性。方法选取2019年1月至2020年1月间,蚌埠医学院第一附属医院感染科收治的80例乙肝肝硬化患者(肝硬化组)、80例单纯乙肝患者(乙肝组)及体检中心80例健康人群(对照组)为研究对象。比较三组肠道菌群变化、肠道菌群丰度和多样性、LPS和血氨的水平,采用Pearson/Spearman相关分析肠道菌群丰度和多样性与肝功能Child-Pugh分级、LPS及血氨之间的相关性,采用受试者工作特征曲线(Receiver operating characteristic,ROC)下面积(Area under the curve,AUC)分析肠道菌群丰度和多样性、LPS、血氨诊断肝性脑病(Hepatic encephalopathy,HE)的效能。结果乙肝组、对照组拟杆菌门、厚壁菌门是肠道菌群的绝对优势菌,在肠道菌群中占比之和>80%,肝硬化组拟杆菌门、厚壁菌门占比低于乙肝组和对照组(P<0.05);变形菌门、梭杆菌门占比:肝硬化组>乙肝组>对照组(P<0.05);Chao指数、LPS:肝硬化组<乙肝组<对照组,Shannon指数、血氨:肝硬化组<乙肝组、对照组(P<0.05);Chao指数、Shannon指数与Child-Pugh分级、LPS、血氨呈负相关(P<0.05);HE患者Chao指数、Shannon指数低于无HE患者,LPS、血氨高于无HE患者(P<0.05);诊断HE的AUC:各指标联合为0.891,血氨为0.825,LPS为0.801,Shannon指数为0.794,Chao指数为0.739(P<0.05)。结论乙肝肝硬化肠道菌群异常与肝功能Child-Pugh分级、LPS和血氨有关,肠道菌群可能参与了肝功能恶化、内毒素血症以及HE并发症的发生与病情进展,肠道菌群Chao指数、Shannon指数有助于HE的诊断,调节肠道菌群有望成为乙肝肝硬化患者治疗方案中的一部分。

Objective To explore the relationship between the changes of intestinal microflora in hepatitis B cirrhosis and liver function Child-Pugh classification,endotoxin(LPS)and blood ammonia.Methods From January 2019 to January 2020,80 patients with hepatitis B cirrhosis(cirrhosis group),80 patients with simple hepatitis B(hepatitis B group)and 80 healthy people(control group)were selected from the Department of Infectious Diseases and Medical Examination Center of the First Affiliated Hospital of Bengbu Medical College.The changes of intestinal flora,abundance and diversity of intestinal flora,LPS and blood ammonia levels in the three groups were compared.Pearson/Spearman was used to analyze the correlation between the abundance and diversity of intestinal flora and liver function Child-Pugh classification,LPS,blood ammonia,and receiver operating characteristic curve(Receiver operating characteristic,ROC)and area under ROC(Area under the curve,AUC)were used to analyze the efficacy of intestinal flora abundance and diversity,LPS,and blood ammonia in the diagnosis of hepatic encephalopathy(Hepatic encephalopathy,HE).Results The Bacteroides phylum and Paecilomyces phylum of the hepatitis B group and the control group were the absolute dominant bacteria of the intestinal flora,and their proportion in the intestinal flora was>80%.The proportion of Bacteroides phylum and Pachythrobacter phylum in the liver cirrhosis group was lower than that in the hepatitis B group and the control group(P<0.05).The proportion of Proteobacteria and Clostridium was shown as follows:cirrhosis group>hepatitis B group>control group(P<0.05).Chao index,LPS:cirrhosis group<hepatitis B group<control group,Shannon index,blood ammonia:cirrhosis group<hepatitis B group and control group(P<0.05).Chao index and Shannon index were negatively correlated with Child-Pugh classification,LPS and blood ammonia(P<0.05).The Chao index and Shannon index of HE patients were lower than those without HE,and LPS and blood ammonia were higher than those without HE(P<0.05).AUC for the diagnosis of HE:the combination of various indicators was 0.891,blood ammonia was 0.825,LPS was 0.801,Shannon index was 0.794,and Chao index was 0.739(P<0.05).Conclusion Abnormal intestinal microflora in hepatitis B cirrhosis is related to liver function Child-Pugh classification,LPS,blood ammonia,and may be involved in the occurrence of liver function deterioration,endotoxemia,HE and other related complications and disease progression.The Chao index and Shannon index of intestinal flora are helpful for the diagnosis of HE,and the regulation of intestinal flora is expected to be a part of the treatment for patients with hepatitis B cirrhosis.