Impact of Rifaximin Therapy on Ischemia/Reperfusion Injury in Liver Transplantation: A Propensity Score-Matched Analysis.

Abstract

Intestinal microbiota is thought to play an important role in hepatic ischemia/reperfusion injury (IRI) after liver transplantation (LT). Rifaximin, a nonabsorbable antibiotic used to treat encephalopathy, exhibits antibacterial activity within the gut. We report the first study examining the impact of pre-LT rifaximin use on reducing hepatic IRI and inflammatory cell infiltration after LT. This retrospective single-center study included adult LT recipients from January 2013 through June 2016. Patients were divided into 2 groups based on duration of rifaximin use before LT: rifaximin group (≥28 days) and control group (none or <28 days). Patients receiving other antibiotics within 28 days of LT and re-LTs were excluded. Outcomes and messenger RNA (mRNA) expression in the graft were compared by 1:1 propensity score-matching and multivariate analyses. On 1:1 matching (n = 39/group), rifaximin patients had lower postoperative serum transaminase levels and lower early allograft dysfunction (EAD; 10.3% versus 33.3%; P = 0.014). Of the matched patients, 8 patients (n = 4/group) had postreperfusion liver biopsies (approximately 2 hours after reperfusion) available for mRNA analysis. Hepatic expression of CD86 (macrophage marker) and cathepsin G (neutrophil marker) was significantly lower in rifaximin patients than controls (P < 0.05). The multivariate analysis included 458 patients. Rifaximin treatment <28 days was identified as an independent risk factor EAD in all patients and those with high Model for End-Stage Liver Disease (MELD) score (MELD ≥35; n = 230). In conclusion, the propensity score-matched and multivariate analyses suggest a therapeutic role of rifaximin in reducing EAD. Pre-LT rifaximin administration exerted a protective function against early liver injury, potentially by suppressing inflammatory cell activation in the graft.

• Authors: Takahiro Ito, Kojiro Nakamura, Shoichi Kageyama, Islam M Korayem, Hirofumi Hirao, Kentaro Kadono, Justine Aziz, Stephanie Younan, Joseph DiNorcia 3rd, Vatche G Agopian, Hasan Yersiz, Douglas G Farmer, Ronald W Busuttil, Jerzy W Kupiec-Weglinski, Fady M Kaldas
• Journal: Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society (Liver Transpl) Vol. 25 Issue 12 Pg. 1778-1789 (12 2019) ISSN: 1527-6473 [Electronic] United States
• PMID: 31509643 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2019 by the American Association for the Study of Liver Diseases.

Chemical References

• Biomarkers
• Rifaximin

Topics

• Adult
• Aged
• Allografts (blood supply, pathology)
• Antibiotic Prophylaxis (methods, statistics & numerical data)
• Biomarkers (analysis)
• Biopsy
• Drug Administration Schedule
• Female
• Gastrointestinal Microbiome (drug effects)
• Graft Rejection (diagnosis, epidemiology, etiology, prevention & control)
• Graft Survival
• Humans
• Liver (blood supply, pathology)
• Liver Function Tests
• Liver Transplantation (adverse effects)
• Male
• Middle Aged
• Postoperative Complications (diagnosis, epidemiology, etiology, prevention & control)
• Preoperative Care (methods, statistics & numerical data)
• Propensity Score
• Reperfusion (adverse effects)
• Reperfusion Injury (diagnosis, epidemiology, etiology, prevention & control)
• Retrospective Studies
• Rifaximin (administration & dosage)
• Risk Factors
• Survival Rate
• Time Factors
• Young Adult