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

Liver Transpl. 2019 Dec;25(12):1778-1789. doi: 10.1002/lt.25633. Epub 2019 Nov 4.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

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

Substances

  • Biomarkers
  • Rifaximin