The Dumont-UCLA Transplantation Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
Department of Surgery, Kyoto University, Kyoto, Japan.
Liver Transpl. 2019 Dec;25(12):1778-1789. doi: 10.1002/lt.25633. Epub 2019 Nov 4.
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.
肠道微生物群被认为在肝移植（LT）后肝脏缺血/再灌注损伤（IRI）中发挥重要作用。利福昔明是一种用于治疗肝性脑病的不可吸收抗生素，在肠道内具有抗菌活性。我们报告了第一项研究，该研究检查了 LT 前使用利福昔明对减轻 LT 后肝脏 IRI 和炎症细胞浸润的影响。这项回顾性单中心研究纳入了 2013 年 1 月至 2016 年 6 月期间接受 LT 的成年患者。根据 LT 前利福昔明使用的持续时间，患者分为两组：利福昔明组（≥28 天）和对照组（无或<28 天）。排除了在 LT 后 28 天内接受其他抗生素和再次 LT 的患者。通过 1:1 倾向评分匹配和多变量分析比较了两组的转归和移植物中的信使 RNA（mRNA）表达。在 1:1 匹配（n=39/组）中，利福昔明组患者术后血清转氨酶水平较低，早期移植物功能障碍（EAD；10.3%对 33.3%；P=0.014）较低。在匹配的患者中，有 8 名患者（n=4/组）在再灌注后（再灌注后约 2 小时）进行了肝活检，用于 mRNA 分析。利福昔明组患者肝组织中 CD86（巨噬细胞标志物）和组织蛋白酶 G（中性粒细胞标志物）的表达明显低于对照组（P<0.05）。多变量分析纳入了 458 名患者。在所有患者和高终末期肝病模型（MELD）评分（MELD≥35；n=230）患者中，LT 前 28 天内接受利福昔明治疗被确定为 EAD 的独立危险因素。总之，倾向评分匹配和多变量分析表明利福昔明在降低 EAD 方面具有治疗作用。LT 前利福昔明给药对早期肝损伤具有保护作用，可能通过抑制移植物中炎症细胞的激活来实现。
