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乙型肝炎肝硬化患者肠道菌群失衡度与肝病严重程度的相关性
作者:王艺璇 1   张珊 2   程丹颖 2   刘顺爱 3   孙静 2   成军 1.2   邢卉春 1 2 
单位:1.北京大学地坛医院教学医院 肝病三科 北京100015 2.首都医科大学附属北京地坛医院 肝病三科 北京 100015 3.首都医科大学附属北京地坛医院新发突发传染病北京市重点实验室 北京 100015 
关键词:菌群失衡 肝炎 乙型 肝硬化 代偿期 肝硬化 失代偿期 
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出版年,卷(期):页码:2019,11(3):8-13
摘要:
摘要:目的 建立乙型肝炎肝硬化患者肠道菌群失衡度参数,评价其与乙型肝炎肝硬化严重程度的相关 性。方法 收集2017年11月至2019年1月首都医科大学附属北京地坛医院招募的健康志愿者、代偿期乙 型肝炎肝硬化与失代偿期乙型肝炎肝硬化患者(各40例)的血液和粪便标本进行检验。根据细菌16S rDNA高通量测序及相关生物信息学技术获得目标菌群相对丰度及差异,选用MetaStat分析有统计学差 异的肠球菌属、链球菌属及乳杆菌属作为分子,参考肠型代表菌属,选择拟杆菌属、普氏菌属及瘤胃 球菌属作为分母,建立乙型肝炎肝硬化肠道菌群失衡度比值(hepatits B cirrhosis dysbiosis indicator, HBCDI)。使用Spearman相关性分析HBCDI与MELD评分、INR的相关性,评价其与肝病严重程度的 相关性。结果 以(肠球菌属 + 链球菌属 + 乳杆菌属)相对丰度/(瘤胃球菌属 + 普氏菌属 + 拟杆菌属) 相对丰度为HBCDI,健康对照组、代偿组和失代偿组HBCDI分别为0.017、0.033及0.357,差异有统计 学意义(H = 3.95,P < 0.001)。HBCDI诊断失代偿期乙型肝炎肝硬化的AUC为0.75,与MELD评分、 INR、TBil的相关系数分别为0.32(P = 0.05)、0.38(P = 0.017)和0.19(P = 0.048)。结论 HBCDI可 反映乙型肝炎肝硬化患者肠道菌群失衡程度,HBCDI越大,肝病越严重。
Abstract: Objective To build the hepatits B cirrhosis dysbiosis indicator (HBCDI) and assess its correlation with the severity of hepatitis B cirrhosis. Methods Blood and feacel samples of healthy controls, patients with compensated cirrhotics, and patients with decompensated cirrhotics (40 cases per group) in Beijing Ditan Hospital, Capital Medical University form November 2017 to January 2019 were collected. 16S rDNA IonS5TMXL sequencing and other bioinformatics were used to get relative abundance of target genuses in order to identify if there was any difference. Enterococcus, Streptococcus and Lactobacillus were selected as numerator which showed significant differences in MetaStat analysis, and Enterotypes Bacteroides, Prevotella, and Ruminococcus were selected as denominator. Spearman analysis was used to analyze the correlation between HBCDI and MELD score, INR, and TBil to evaluat its correlation with the severity of liver cirrhosis. Results The computational formula of HBCDI was the ratio of the relative abundance of (Enterococcus + Streptococcus + Lactobacillus) and the relative abundance of (Ruminococcus + Prevotella +Bacteroides). The HBCDI of objects in healthy group, compensated group and decompensated group were 0.017, 0.033 and 0.357, respectively, the difference was statistically significant (H = 3.95, P < 0.001). The AUC of HBCDI to diagnose hepatitis B decompensated cirrhosis was 0.75 and its correlation coefficients with MELD score, INR, and total bilirubin were 0.32 (P = 0.05), 0.38 (P = 0.017) and 0.19 (P = 0.048), respectively. Conclusion HBCDI is an important index reflecting the gut dysbiosis of hepatitis B cirrhosis. The bigger the HBCDI, the more serious the liver disease.
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