Ischemia‐reperfusion injury (IRI) is believed to contribute to graft dysfunction after liver transplantation (LT). However, studies on IRI and the impact of early allograft dysfunction (EAD) in IRI grafts are limited. Histological IRI was graded in 506 grafts from patients who had undergone LT and classified based on IRI severity (no, minimal, mild, moderate, and severe). Of the 506 grafts, 87.4% had IRI (no: 12.6%, minimal: 38.1%, mild: 35.4%, moderate: 13.0%, and severe: 0.8%). IRI severity correlated with the incidence of EAD and graft survival at 6 months. Longer cold/warm ischemia time, recipient/donor hypertension, and having a male donor were identified as independent risk factors for moderate to severe IRI. Among 70 grafts with moderate to severe IRI, 42.9% of grafts developed EAD, and grafts with EAD had significantly inferior survival compared to grafts without EAD. Longer cold ischemia time and large droplet macrovesicular steatosis (≥20%) were identified as independent risk factors for EAD. Our study demonstrated that increased IRI severity was correlated with inferior short‐term graft outcomes. Careful consideration of IRI risk factors during donor‐recipient matching may assist in optimizing graft utilization and LT outcomes. Furthermore, identification of risk factors of IRI‐associated EAD may guide patient management and possible timely graft replacement.
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.
Marijuana is one of the most commonly used illicit drugs worldwide. 1 Currently in the United States, medicinal marijuana use is legal in thirty-three states and recreational use is legal in eleven states. 2 In the past year, 15.9% of Americans aged 12 years or older used marijuana, a rate higher than any previously reported. 3 However, despite such widespread political and social acceptance, marijuana use remains a controversial topic in liver transplant (LT), 4 challenging LT programs to devise equitable substance abuse policies pertaining to candidates with active marijuana use.
Background Although the use of extended criteria donor (ECD) liver allografts has gained momentum as a potential method by which to expand the donor pool, their use largely remains relegated to low acuity liver transplant (LT) recipients. Thus, we sought to examine whether such grafts also have utility in high acuity (Model for End-Stage Liver Disease [MELD] ≥ 35) recipients. Study Design Extended criteria donors were defined as donor age > 60 years, hepatitis C virus positive donor, split livers, livers with cold ischemia time > 12 h, donor after cardiac death livers, or having macrosteatosis > 30%. Outcomes were compared between standard liver (SL) and ECD grafts in recipients with MELD ≥ 35. Results Of 225 patients, 46 (20.4%) received an ECD liver and 179 (79.6%) received a SL. Extended criteria donor graft recipients had significantly higher levels of post-LT maximal transaminases and rate of early allograft dysfunction. Nonetheless, high acuity ECD graft recipients had similar short- and long-term patient survival compared to SL recipients, with 1-,3-, and 5-year survivals of 86.9%, 82.3%, 79.3% and 86.9%, 80.5%, and 75.4%, respectively ( P = .674). There were also no significant differences in graft survival or rejection-free survival between the 2 groups. Conclusion The lack of inferior patient/graft survival among high acuity ECD graft recipients suggests that ECD livers present a viable method by which to expand the donor pool for this group of patients.
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