Banff 2022 Liver Group Meeting report: Monitoring long-term allograft health.

The Banff Working Group on Liver Allograft Pathology met in September 2022. Participants included hepatologists, surgeons, pathologists, immunologists, and histocompatibility specialists. Presentations and discussions focused on the evaluation of long-term allograft health, including noninvasive and tissue monitoring, immunosuppression optimization, and long-term structural changes. Potential revision of the rejection classification scheme to better accommodate and communicate late T cell-mediated rejection patterns and related structural changes, such as nodular regenerative hyperplasia, were discussed. Improved stratification of long-term maintenance immunosuppression to match the heterogeneity of patient settings will be central to improving long-term patient survival. Such personalized therapeutics are in turn contingent on a better understanding and monitoring of allograft status within a rational decision-making approach, likely to be facilitated in implementation with emerging decision-support tools. Proposed revisions to rejection classification emerging from the meeting include the incorporation of interface hepatitis and fibrosis staging. These will be opened to online testing, modified accordingly, and subject to consensus discussion leading up to the next Banff conference.

The demise of islet allotransplantation in the United States: A call for an urgent regulatory update.

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and "more than minimally manipulated" human cell and tissue products (HCT/Ps). In contrast, across the world, human islets are appropriately defined as "minimally manipulated tissue" and not regulated as a drug, which has led to islet allotransplantation (allo-ITx) becoming a standard-of-care procedure for selected patients with type 1 diabetes mellitus. This regulatory distinction impedes patient access to islets for transplantation in the US. As a result only 11 patients underwent allo-ITx in the US between 2016 and 2019, and all as investigational procedures in the settings of a clinical trials. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States.

Assessment of simple indices based on a single fasting blood sample as a tool to estimate beta-cell function after total pancreatectomy with islet autotransplantation - a prospective study.

We investigated six indices based on a single fasting blood sample for evaluation of the beta-cell function after total pancreatectomy with islet autotransplantation (TP-IAT). The Secretory Unit of Islet Transplant Objects (SUITO), transplant estimated function (TEF), homeostasis model assessment (HOMA-2B%), C-peptide/glucose ratio (CP/G), C-peptide/glucose creatinine ratio (CP/GCr) and BETA-2 score were compared against a 90-min serum glucose level, weighted mean C-peptide in mixed meal tolerance test (MMTT), beta score and the Igls score adjusted for islet function in the setting of IAT. We analyzed values from 32 MMTTs in 15 patients after TP-IAT with a follow-up of up to 3 years. Four (27%) individuals had discontinued insulin completely prior to day 75, while 6 out of 12 patients (50%) did not require insulin support at 1-year follow-up with HbA1c 6.0% (5.5-6.8). BETA-2 was the most consistent among indices strongly correlating with all reference measures of beta-cell function (r = 0.62-0.68). In addition, it identified insulin independence (cut-off = 16.2) and optimal/good versus marginal islet function in the Igls score well, with AUROC of 0.85 and 0.96, respectively. Based on a single fasting blood sample, BETA-2 score has the most reliable discriminant value for the assessment of graft function in patients undergoing TP-IAT.

A Comparison of the Initial Cost Associated With Resection Versus Laparoscopic Radiofrequency Ablation of Small Solitary Colorectal Liver Metastasis.

INTRODUCTION: The aim of this report was to perform a cost-comparison between liver resection (LR) and radiofrequency ablation (RFA). METHOD: Patients with colorectal liver metastasis (CRLM)≤3 cm, who underwent LR or laparoscopic RFA between 2006 and 2015 were included in the study. Using a prospectively maintained CRLM database, clinical, oncologic, and financial parameters were compared. RESULTS: Sixty-three patients underwent open or laparoscopic LR, and 25 patients underwent laparoscopic RFA. No significant difference was noted in postoperative complications, readmission rate, and local recurrence rate. With a median follow-up of 40 months for RFA, and 36 months for LR (P=0.61), mean cancer-specific overall survival was 51 months for RFA and 63 months for LR (P=0.64). The median disease-free survival was 14 months for RFA, and 21 months for LR (P=0.59). The mean operating room and hospital costs were 51% and 55% higher in the LR (P<0.001, each). CONCLUSIONS: The results of the study suggest that in selected patients with small solitary CRLM, laparoscopic tumor ablation might offer opportunities for cost-savings compared with resection as the primary treatment. This model may suggest possible equivalent oncologic outcomes between the 2 modalities.

Lipid metabolism and functional assessment of discarded human livers with steatosis undergoing 24 hours of normothermic machine perfusion.

Normothermic machine perfusion (NMP) is an emerging technology to preserve liver allografts more effectively than cold storage (CS). However, little is known about the effect of NMP on steatosis and the markers indicative of hepatic quality during NMP. To address these points, we perfused 10 discarded human livers with oxygenated NMP for 24 hours after 4-6 hours of CS. All livers had a variable degree of steatosis at baseline. The perfusate consisted of packed red blood cells and fresh frozen plasma. Perfusate analysis showed an increase in triglyceride levels from the 1st hour (median, 127 mg/dL; interquartile range [IQR], 95-149 mg/dL) to 24th hour of perfusion (median, 203 mg/dL; IQR, 171-304 mg/dL; P = 0.004), but tissue steatosis did not decrease. Five livers produced a significant amount of bile (≥5 mL/hour) consistently throughout 24 hours of NMP. Lactate in the perfusate cleared to <3 mmol/L in most livers within 4-8 hours of NMP, which was independent of bile production rate. This is the first study to characterize the lipid profile and functional assessment of discarded human livers at 24 hours of NMP. Liver Transplantation 24 233-245 2018 AASLD.

Effect of Early Everolimus-Facilitated Reduction of Tacrolimus on Efficacy and Renal Function in De Novo Liver Transplant Recipients: 24-Month Results for the North American Subpopulation.

BACKGROUND: A recent randomized phase III study of 719 de novo liver transplant recipients showed that early everolimus plus reduced-dose tacrolimus (EVR + rTAC) led to significantly better kidney function than standard TAC (TAC-C), without compromising efficacy. In that study, patients from North America (n = 211) had increased risk factors for posttransplant renal insufficiency at study start, relative to patients from Europe and rest of world (eg, worse renal function, more diabetes, older age). METHODS: A post hoc analysis was performed to assess whether these regional disparities affected study outcomes in North American patients. RESULTS: In this subpopulation, estimated glomerular filtration rates at randomization were higher in TAC-C over EVR + rTAC (76.4 vs 69.3 mL/min per 1.73 m). Mean changes in estimated glomerular filtration rate values (mL/min per 1.73 m) favored EVR + rTAC over TAC-C at months 12 (+3.7 vs -4.5; P = 0.032), 24 (+2.7 vs -6.6; P = 0.042), and 36 (+4.3 vs -8.1; P = 0.059). The composite efficacy endpoint of treated biopsy-proven acute rejection, graft loss, or death was 10.9%, 14.1%, and 14.1% for EVR + rTAC and 13.1%, 17.2%, and 19.3% for TAC-C at months 12, 24, and 36, respectively. CONCLUSIONS: Although the North American cohort had more comorbidities, results were consistent with the overall population for efficacy and renal function.

The Cleveland Clinic FACES Score: a preliminary assessment tool for identifying the optimal face transplant candidate.

In lieu of limited resources, our multidisciplinary face transplant team requires a preliminary, supplemental objective grading scheme for identifying the optimal face transplant candidate. Therefore, our objective was to develop an effective method for evaluating "facial deficit," which could also be used in the future for the allocation of limited facial organs, analogous to liver transplantation.Each candidate is screened using our institutional review board-approved protocol's current inclusion/exclusion criteria. Five categories were conceptualized to be of significance in evaluating patients in pursuit of facial allotransplantation as per our recent experience, as determined by the face transplant team. All patients with unfavorable characteristics such as evidence of poor medical compliance, an unsatisfactory psychosocial evaluation by our team's transplant psychiatrist, and/or end-stage organ disease suggestive of significant comorbidity were excluded.This study resulted in a reproducible scoring system allowing our team the unprecedented ability to stratify facial deficit in a standardized fashion. The FACES scores ranged from 10 (minimum) to 60 (maximum). Besides being used as a supplemental prescreening and/or postscreening tool, the FACES score has also provided an unprecedented framework for establishing a face transplant candidate registry within our institution, with the optimal recipients receiving the highest of scores.This FACES score objectively stratifies face transplant candidates for their facial deficit during multiple steps throughout the screening process and affords our institution the means of creating a registry. If substantiated, this supplemental score may ultimately predict successful outcomes, determine optimal utility, and provide insight toward prognosis with respect to facial composite tissue allotransplantation.