Restoration of the gut microbiota is associated with a decreased risk of hepatic encephalopathy after TIPS

Menghao Li; Kai Li; Shihao Tang; Yong Lv; Qiuhe Wang; Zhengyu Wang; Bohan Luo; Jing Niu; Ying Zhu; Wengang Guo; Wei Bai; Enxin Wang; Dongdong Xia; Zhexuan Wang; Xiaomei Li; Jie Yuan; Zhanxin Yin; Jonel Trebicka; Guohong Han

doi:10.1016/j.jhepr.2022.100448

Restoration of the gut microbiota is associated with a decreased risk of hepatic encephalopathy after TIPS

JHEP Rep. 2022 Feb 15;4(5):100448. doi: 10.1016/j.jhepr.2022.100448. eCollection 2022 May.

Authors

Menghao Li¹, Kai Li¹, Shihao Tang¹, Yong Lv¹, Qiuhe Wang¹, Zhengyu Wang^{1

2}, Bohan Luo^{1

2}, Jing Niu¹, Ying Zhu^{1

2}, Wengang Guo^{1

2}, Wei Bai^{1

2}, Enxin Wang¹, Dongdong Xia^{1

2}, Zhexuan Wang¹, Xiaomei Li^{1

2}, Jie Yuan¹, Zhanxin Yin^{1

2}, Jonel Trebicka^{3

4}, Guohong Han^{1

2}

Affiliations

¹ Department of Liver Diseases and Digestive Interventional Radiology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
² Department of Liver Diseases and Interventional Radiology, Digestive Diseases Hospital, Xi'an International Medical Center Hospital, Northwest University, Xi'an, China.
³ University Hospital Frankfurt, Department of Internal Medicine I, Goethe University, Frankfurt, Germany.
⁴ European Foundation for the Study of Chronic Liver Failure (EFCLIF), Barcelona, Spain.

Abstract

Background & aims: Hepatic encephalopathy (HE) is a major complication after transjugular intrahepatic portosystemic shunt (TIPS) and is primarily influenced by the gut microbiota. We aimed to evaluate alterations in the microbiota after TIPS and the association between such alterations and HE.

Methods: We conducted a prospective longitudinal study of 106 patients with cirrhosis receiving TIPS. Faecal samples were collected before and after TIPS, and the gut microbiota was analysed by 16S ribosomal RNA sequencing.

Results: Among all patients, 33 developed HE (HE+ group) within 6 months after TIPS and 73 did not (HE- group), and 18 died during follow-up. After TIPS, the autochthonous taxa increased, whereas the potential pathogenic taxa decreased in the HE- group, and the autochthonous taxon Lachnospiraceae decreased in the HE+ group. Furthermore, synergism among harmful bacteria was observed in all patients, which was weakened in the HE- group (p <0.001) but enhanced in the HE+ group (p <0.01) after TIPS. Variations of 5 autochthonous taxa, namely, Coprococcus, Ruminococcus, Blautia, Ruminococcaceae_uncultured, and Roseburia, were negatively correlated with the severity of HE. Notably, increased abundances of Coprococcus and Ruminococcus were protective factors against HE, and the incidences of HE in patients with improved, stable, and deteriorated microbiota after TIPS were 13.3, 25.9, and 68.2%, respectively. Higher total bilirubin level, Child-Pugh score, model for end-stage liver disease score, Granulicatella, and Alistipes and lower Subdoligranulum before TIPS were the independent risk factors for death.

Conclusions: Alterations in gut dysbiosis were negatively related to the occurrence and severity of post-TIPS HE, and the pre-TIPS microbiota were associated with death, suggesting the gut microbiota could be a promising potential biological target for screening suitable patients receiving TIPS and prevention and treatment of post-TIPS HE.

Lay summary: Alterations in the gut microbiota after transjugular intrahepatic portosystemic shunt (TIPS) and the relationship between such alterations and post-TIPS hepatic encephalopathy (HE) remain unclear. We therefore performed this study and found that after TIPS, restoration of the gut microbiota, mainly characterised by expansion of autochthonous taxa, depletion of harmful taxa, and weakening of synergism among harmful bacteria, was inversely related to the occurrence and severity of post-TIPS HE.

Keywords: ACLF, acute-on-chronic liver failure; ALP, alkaline phosphatase; ALT, alanine aminotransferase; ANOSIM, analysis of similarities; AST, aspartate aminotransferase; BUN, blood urea nitrogen; ChiCTR, Chinese Clinical Trial Registry; Cirrhosis; Cr, creatinine; FDR, false discovery rate; FMT, faecal microbiota transplantation; GGT, gamma-glutamyl transpeptidase; Gut microbiota; HE, hepatic encephalopathy; HGB, haemoglobin; Hepatic encephalopathy; KEGG, Kyoto Encyclopedia of Genes and Genomes; LDA, linear discriminant analysis; LEfSe, linear discriminant analysis effect size; MELD, model for end-stage liver disease; NMDC, China National Microbiology Data Center; OLT, orthotopic liver transplantation; OR, odds ratio; OTU, operational taxonomic unit; PCoA, principal coordinate analysis; PICRUSt, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States; PPG, portosystemic pressure gradient; PPI, proton pump inhibitor; PSM, propensity score matching; Portal hypertension; RDA, redundancy analysis; RDP, Ribosomal Database Project; SCFA, short-chain fatty acid; TB, total bilirubin; TIPS, transjugular intrahepatic portosystemic shunt; Transjugular intrahepatic portosystemic shunt; rRNA, ribosomal RNA.