Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA. Microbiology, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA. Microbiome Analysis Center, George Mason University, Manassas, VA, USA.
Am J Gastroenterol. 2018 Aug;113(8):1177-1186. doi: 10.1038/s41395-018-0085-9. Epub 2018 Jun 6.
Cirrhosis is associated with gut microbial dysbiosis, high readmissions and proton pump inhibitor (PPI) overuse, which could be inter-linked. Our aim was to determine the effect of PPI use, initiation and withdrawl on gut microbiota and readmissions in cirrhosis.
Four cohorts were enrolled. Readmissions study: Cirrhotic inpatients were followed throughout the hospitalization and 30/90-days post-discharge. PPI initiation, withdrawal/continuation patterns were analyzed between those with/without readmissions. Cross-sectional microbiota study: Cirrhotic outpatients and controls underwent stool microbiota analysis. Beneficial autochthonous and oral-origin taxa analysis vis-à-vis PPI use was performed. Longitudinal studies: Two cohorts of decompensated cirrhotic outpatients were enrolled. Patients on chronic unindicated PPI use were withdrawn for 14 days. Patients not on PPI were started on omeprazole for 14 days. Microbial analysis for oral-origin taxa was performed pre/post-intervention.
Readmissions study: 343 inpatients (151 on admission PPI) were enrolled. 21 were withdrawn and 45 were initiated on PPI resulting in a PPI use increase of 21%. PPIs were associated with higher 30 (p = 0.002) and 90-day readmissions (p = 0.008) independent of comorbidities, medications, MELD and age. Cross-sectional microbiota: 137 cirrhotics (59 on PPI) and 45 controls (17 on PPI) were included. PPI users regardless of cirrhosis had higher oral-origin microbiota while cirrhotics on PPI had lower autochthonous taxa compared to the rest. Longitudinal studies: Fifteen decompensated cirrhotics tolerated omeprazole initiation with an increase in oral-origin microbial taxa compared to baseline. PPIs were withdrawn from an additional 15 outpatients, which resulted in a significant reduction of oral-origin taxa compared to baseline.
PPIs modulate readmission risk and microbiota composition in cirrhosis, which responds to withdrawal. The systematic withdrawal and judicious use of PPIs is needed from a clinical and microbiological perspective in decompensated cirrhosis.
肝硬化与肠道微生物失调、高再入院率和质子泵抑制剂（PPI）过度使用有关，这些因素可能相互关联。我们的目的是确定 PPI 的使用、启动和停用对肝硬化患者肠道微生物群和再入院的影响。
共纳入了 4 个队列。再入院研究：对肝硬化住院患者进行了全程住院和出院后 30/90 天的随访。分析了再入院患者和未再入院患者之间的 PPI 使用、启动和停用模式。横断面微生物组学研究：对肝硬化门诊患者和对照者进行了粪便微生物组分析。分析了有益的本土和口腔来源分类群与 PPI 使用的关系。纵向研究：纳入了两批失代偿期肝硬化门诊患者。对长期未使用 PPI 的患者进行了 14 天的停药。对未使用 PPI 的患者进行了 14 天的奥美拉唑治疗。在干预前后进行了口腔来源分类群的微生物分析。
再入院研究：共纳入 343 例住院患者（151 例入院时使用 PPI）。21 例患者停用 PPI，45 例患者开始使用 PPI，PPI 使用增加了 21%。PPI 与较高的 30 天（p=0.002）和 90 天再入院率（p=0.008）相关，与合并症、药物、MELD 和年龄无关。横断面微生物组学研究：共纳入 137 例肝硬化患者（59 例使用 PPI）和 45 例对照者（17 例使用 PPI）。无论是否患有肝硬化，使用 PPI 的患者口腔来源的微生物群更多，而使用 PPI 的肝硬化患者本土分类群较少。纵向研究：15 例失代偿期肝硬化患者耐受了奥美拉唑的起始治疗，与基线相比，口腔来源的微生物群增加。另外 15 例门诊患者停用了 PPI，与基线相比，口腔来源的微生物群显著减少。
PPI 可调节肝硬化患者的再入院风险和微生物群组成，且停药后可恢复。从临床和微生物学的角度来看，在失代偿期肝硬化患者中需要系统地停用和谨慎使用 PPI。
