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人工肝支持系统对乙型肝炎病毒相关慢加急性肝衰竭患者肠道菌群的影响

Effect of Artificial Liver Support Systems on Gut Microbiota in Patients with HBV-Related Acute-on-Chronic Liver Failure.

作者信息

Song Zhiying, Xie Qiong, Zhou Yao, Song Shufen, Gao Zhen, Lan Yu, Wu Zhiguo, Cai Hongxin, Yu Dongshan, Liu Cuiyun, Liang Junrong, Xie Baogang, Sun Shuilin

机构信息

Department of Infectious Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.

School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311400, China.

出版信息

Pathogens. 2023 Aug 28;12(9):1094. doi: 10.3390/pathogens12091094.

Abstract

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a rare and severe form of end-stage liver disease with high mortality; gut microbes are strongly associated with the development of this severe liver disease but the exact association is unclear. Artificial liver support systems (ALSS) are clinically important in prolonging the waiting time for liver transplantation and in aiding drug therapy to achieve remission. The aim of this study was to investigate the effect of ALSS on the abundance and diversity of microorganisms in the gut of HBV-ACLF patients. In this study, 109 stool samples were collected from patients with hepatitis B virus-associated acute chronic liver failure (HBV-ACLF) for 16S rRNA sequencing. Among them, 44 samples were from patients treated with ALSS therapy as an adjunct to standard medical treatment (SMT) and 65 were from patients receiving SMT only. Analysis of the sequencing results suggested that there were significant differences in the abundance and diversity of gut microbiota between the with-ALSS and without-ALSS groups ( < 0.05). The operational taxonomic units and Shannon indexes indicated that the diversity and abundance of the gut microbiome, while decreasing after the first ALSS treatment, gradually increased after an increase in the number of ALSS therapies. The overall proportion of HBV-ACLF patients with coinfection was 27.59%; the coinfection can reduce the abundance of the phylum in the microbiome significantly whereas were highly enriched. After ALSS therapy, HBV-ACLF patients had a decrease in potentially harmful bacteria, an increase in potentially beneficial bacteria, an increase in the diversity of the intestinal microbiota, and the intestinal microecological disorders were corrected to a certain extent. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) levels, as well as the international normalized ratio (INR), showed a decreasing trend whereas plasminogen activity (PTA) increased and the condition of patients with HBV-ACLF progressed in a favorable direction. In addition, the abundance of and was negatively correlated with TBIL and INR, positively correlated with PTA, and positively correlated with disease recovery. Our study shows that ALSS can alter the composition of the gut microbiota and have an ameliorating effect on the gut microecological imbalance in HBV-ACLF patients. It is worth mentioning that and may have great potential as biomarkers.

摘要

乙型肝炎病毒相关慢加急性肝衰竭(HBV-ACLF)是一种罕见且严重的终末期肝病形式,死亡率很高;肠道微生物与这种严重肝病的发生密切相关,但确切关联尚不清楚。人工肝支持系统(ALSS)在延长肝移植等待时间以及辅助药物治疗以实现缓解方面具有重要临床意义。本研究旨在探讨ALSS对HBV-ACLF患者肠道微生物丰度和多样性的影响。在本研究中,收集了109份乙型肝炎病毒相关慢加急性肝衰竭(HBV-ACLF)患者的粪便样本进行16S rRNA测序。其中,44份样本来自接受ALSS治疗作为标准药物治疗(SMT)辅助治疗的患者,65份来自仅接受SMT治疗的患者。测序结果分析表明,接受ALSS治疗组和未接受ALSS治疗组之间肠道微生物群的丰度和多样性存在显著差异(<0.05)。操作分类单元和香农指数表明,肠道微生物组的多样性和丰度在首次ALSS治疗后降低,但随着ALSS治疗次数增加逐渐升高。HBV-ACLF合并感染患者的总体比例为27.59%;合并感染可显著降低微生物组中某一门的丰度,而另一门类高度富集。经过ALSS治疗后,HBV-ACLF患者潜在有害细菌减少,潜在有益细菌增加,肠道微生物群多样性增加,肠道微生态紊乱得到一定程度纠正。血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和总胆红素(TBIL)水平以及国际标准化比值(INR)呈下降趋势,而纤溶酶原活性(PTA)升高,HBV-ACLF患者病情呈向好方向发展。此外,某两个门类的丰度与TBIL和INR呈负相关,与PTA呈正相关,与疾病恢复呈正相关。我们的研究表明,ALSS可以改变肠道微生物群的组成,并对HBV-ACLF患者的肠道微生态失衡具有改善作用。值得一提的是,某两个门类可能具有作为生物标志物的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c53/10534758/7790865cc1df/pathogens-12-01094-g001.jpg

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