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Existing literature offers conflicting conclusions about whether early acute cellular rejection influences long-term outcomes in liver transplantation. We retrospectively collected donor and recipient data on all adult, first-time liver transplants performed at a single center between 2008 and 2020. We divided this population into two cohorts based on the presence of early biopsy-proven acute cellular rejection (EBPR) within the first 90 days post-transplant and compared outcomes between the groups. There were 896 liver transplants that met inclusion criteria with 112 cases (12.5%) of EBPR. Recipients who developed EBPR had higher biochemical Model for End-Stage Liver Disease scores (28 vs. 24, p < .01), but other donor and recipient characteristics were similar. Recipients with EBPR had similar overall survival compared to patients without EBPR (p = .09) but had decreased graft survival (p < .05). EBPR was also associated with decreased time to first episode of late (> 90 days post-transplant) rejection (p < .0001) and increased vulnerability to bacterial and viral infection (p < .05). In subgroup analysis of recipients with autoimmune indications for liver transplantation, EBPR had a more pronounced association with patient death (hazard ratio [HR] 3.9, p < .05) and graft loss (HR 4.0, p < .01). EBPR after liver transplant is associated with inferior graft survival, increased susceptibility to late rejections, and increased vulnerability to infection., (© 2023 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Histone/protein deacetylases (HDAC) 1 and 2 are typically viewed as structurally and functionally similar enzymes present within various co-regulatory complexes. We tested differential effects of these isoforms in renal ischemia reperfusion injury (IRI) using inducible knockout mice and found no significant change in ischemic tolerance with HDAC1 deletion, but mitigation of ischemic injury with HDAC2 deletion. Restriction of HDAC2 deletion to the kidney via transplantation or PAX8-controlled proximal renal tubule-specific Cre resulted in renal IRI protection. Pharmacologic inhibition of HDAC2 increased histone acetylation in the kidney but did not extend renal protection. Protein analysis demonstrated increased HDAC1-associated CoREST protein in HDAC2-/- versus WT cells, suggesting that in the absence of HDAC2, increased CoREST complex occupancy of HDAC1 can stabilize this complex. In vivo administration of a CoREST inhibitor exacerbated renal injury in WT mice and eliminated the benefit of HDAC2 deletion. Gene expression analysis of endothelin showed decreased endothelin levels in HDAC2 deletion. These data demonstrate that contrasting effects of HDAC1 and 2 on CoREST complex stability within renal tubules can affect outcomes of renal IRI and implicate endothelin as a potential downstream mediator.

Machine perfusion (MP) has emerged as a promising preservation technique to reduce the risks associated with transplant of high risk (steatotic, elderly, and donation after circulatory death) hepatic allografts. Multiple strategies for MP are under investigation. MP facilitates assessment of organ viability and enables liver-directed therapy before transplant. Clinical trials suggest MP may improve the use of hepatic allografts, mitigate ischemia-reperfusion injury, and reduce the incidences of early allograft dysfunction, biliary complications, and ischemic cholangiopathy. As MP sees more widespread use outside of trial settings, more investigation will be needed to establish optimal application of this technology., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The new kidney allocation system (KAS) prioritizes patients based on date of dialysis initiation or waitlisting, whichever is earlier. We hypothesized that this change would increase transplant rates for patients with prolonged pretransplant dialysis times (DT) and aimed to assess the impact of prolonged DT on post-transplant outcomes., Methods: We used United Network for Organ Sharing registry data to assess outcomes for patients added to the renal transplant waitlist from January 1, 1998 to December 31, 2010 and patients transplanted from January 1, 1998 to December 3, 2012., Results: Compared with patients transplanted pre-emptively, patients with <5 years, 5-9 years, and ≥10 years DT had progressively decreased graft and patient survival (P < .001). The rates of short-term complications including delayed graft function, graft loss within 30 days, and patient death within 30 days were significantly higher in cohorts with ≥10 years DT than in cohorts with less DT (P < .001)., Conclusions: Patients with pretransplant DT of ≥10 years had worse outcomes than patients pre-emptively transplanted or transplanted with shorter DT. Durations of dialysis dependence beyond 10 years were associated with further deterioration in short-term but not long-term post-transplant outcomes., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: This study aimed to compare the incidence of radiologically unrecognized (occult) hepatocellular carcinoma (HCC) lesions in explant hepatectomy specimens from orthotopic liver transplants (OLTs) performed for HCC with rates of HCC intrahepatic recurrence after resection., Summary of Background Data: Resection of HCC is associated with high rates of intrahepatic HCC recurrence. However, it is unclear whether these recurrences represent incomplete resection of unrecognized metastatic lesions from the primary tumor or subsequent de novo tumor formation due to inherent biological proclivity for HCC formation., Methods: We collected patient, tumor, and pathology data on HCC patients treated surgically from 3696 OLTs in the Organ Procurement and Transplantation (OPTN) national database, 299 OLTs at a single transplant center, and 232 partial hepatectomies from a hepatobiliary cancer center., Results: In the OPTN and high-volume transplant center cohorts, 37% and 42% of patients had occult HCC lesions on explant pathology, respectively. Among cancer center patients, the 2-year recurrence rate was 46%, and 74% of patients who recurred presented with liver only recurrence., Conclusion: Although the transplant and resection populations differ, occult multifocality is common in transplant explants and similar to the 46% early recurrence rate following partial hepatectomy. These data suggest that noncurative resection often results from occult intrahepatic multifocality present at the time of resection rather than a malignant predisposition of the remnant liver with de novo tumorigenesis.

Early studies of national data suggest that the Share 35 allocation policy increased liver transplants without compromising posttransplant outcomes. Changes in center-specific volumes and practice patterns in response to the national policy change are not well characterized. Understanding center-level responses to Share 35 is crucial for optimizing the policy and constructing effective future policy revisions. Data from the United Network for Organ Sharing were analyzed to compare center-level volumes of allocation-Model for End-Stage Liver Disease (aMELD) ≥ 35 transplants before and after policy implementation. There was significant center-level variation in the number and proportion of aMELD ≥ 35 transplants performed from the pre- to post-Share 35 period; 8 centers accounted for 33.7% of the total national increase in aMELD ≥ 35 transplants performed in the 2.5-year post-Share 35 period, whereas 25 centers accounted for 65.0% of the national increase. This trend correlated with increased listing at these centers of patients with Model for End-Stage Liver Disease (MELD) ≥ 35 at the time of initial listing. These centers did not overrepresent the total national volume of liver transplants. Comparison of post-Share 35 aMELD to calculated time-of-transplant (TOT) laboratory MELD scores showed that only 69.6% of patients transplanted with aMELD ≥ 35 maintained a calculated laboratory MELD ≥ 35 at the TOT. In conclusion, Share 35 increased transplantation of aMELD ≥ 35 recipients on a national level, but the policy asymmetrically impacted practice patterns and volumes of a subset of centers. Longer-term data are necessary to assess outcomes at centers with markedly increased volumes of high-MELD transplants after Share 35. Liver Transplantation 23 741-750 2017 AASLD., (© 2017 by the American Association for the Study of Liver Diseases.)

Experimentally, females show an improved ability to recover from ischemia-reperfusion injury (IRI) compared with males; however, this sex-dependent response is less established in humans. Here, we developed a series of murine renal ischemia and transplant models to investigate sex-specific effects on recovery after IRI. We found that IRI tolerance is profoundly increased in female mice compared with that observed in male mice and discovered an intermediate phenotype after neutering of either sex. Transplantation of adult kidneys from either sex into a recipient of the opposite sex followed by ischemia at a remote time resulted in ischemia recovery that reflected the sex of the recipient, not the donor, revealing that the host sex determines recovery. Likewise, renal IRI was exacerbated in female estrogen receptor α-KO mice, while female mice receiving supplemental estrogen before ischemia were protected. We examined data from the United Network for Organ Sharing (UNOS) to determine whether there is an association between sex and delayed graft function (DGF) in patients who received deceased donor renal transplants. A multivariable logistic regression analysis determined that there was a greater association with DGF in male recipients than in female recipients. Together, our results demonstrate that sex affects renal IRI tolerance in mice and humans and indicate that estrogen administration has potential as a therapeutic intervention to clinically improve ischemia tolerance.

Cardiac arrest associated with reperfusion of the liver allograft in a euvolemic patient is a rare but potentially devastating event. There are few case series describing experience with this complication and no published management protocols guiding treatment. This article is a retrospective case series of patients experiencing post-reperfusion intraoperative cardiac arrest between 1997 and 2011. Among 1581 liver transplants, 16 (1%) patients experienced post-reperfusion cardiac arrest. Among patients with intraoperative arrests, 14 (88%) patients required open cardiac massage. Seven (44%) were placed on cardiopulmonary bypass (CPB) when cardiac activity failed to adequately recover. Placement on CPB reversed cardiac pump failure and established a perfusing rhythm in six of seven (86%) recipients, leading to one of seven (14%) intraoperative mortality. Recovery of myocardial function was associated with low early survival with only 3/7 (43%) patients who underwent CPB surviving until discharge. Among all patients who survived the perioperative period, one-yr survival was 70% (N = 7), and five-yr survival was 50% (N = 5). Cardiac arrest during liver transplantation is associated with a poor prognosis during the perioperative period. In patients who do not recover cardiac activity after standard resuscitative measures, progression to physiologic support with systemic anticoagulation and CPB may allow correction of electrolyte derangements, maintenance of cerebral perfusion, and myocardial recovery., (© 2012 John Wiley & Sons A/S.)

Background: Surgical debridement and antibiotics are the mainstays of therapy for patients with necrotizing soft tissue infections (NSTIs), but hyperbaric oxygen therapy (HBO) is often used as an adjunctive measure. Despite this, the efficacy of HBO remains unclear. We hypothesized that HBO would have no effect on mortality or amputation rates., Methods: We performed a retrospective analysis of our institutional experience from 2005 to 2009. Inclusion criteria were age > 18 y and discharge diagnosis of NSTI. We abstracted baseline demographics, physiology, laboratory values, and operative course from the medical record. The primary endpoint was in-hospital mortality; the secondary endpoint was extremity amputation rate. We compared baseline variables using Mann-Whitney, chi-square, and Fisher's exact test, as appropriate. Significance was set at P < 0.05., Results: We identified 80 cases over the study period. The cohort was 54% male (n = 43) and 53% white (n = 43), and had a mean age of 55 ± 16 y. There were no significant differences in demographics, physiology, or comorbidities between groups. In-hospital mortality was not different between groups (16% in the HBO group versus 19% in the non-HBO group; P = 0.77). In patients with extremity NSTI, the amputation rate did not differ significantly between patients who did not receive HBO and those who did (17% versus 25%; P = 0.46)., Conclusions: Hyperbaric oxygen therapy does not appear to decrease in-hospital mortality or amputation rate after in patients with NSTI. There may be a role for HBO in treatment of NSTI; nevertheless, consideration of HBO should never delay operative therapy. Further evidence of efficacy is necessary before HBO can be considered the standard of care in NSTI., (Copyright © 2012 Elsevier Inc. All rights reserved.)