Heimbach, Julie K.

Background. Early allograft dysfunction (EAD) affects outcomes in liver transplantation (LT). Existing risk models developed for deceased-donor LT depend on posttransplant factors and fall short in living-donor LT (LDLT), where pretransplant evaluations are crucial for preventing EAD and justifying the donor’s risks. Methods. This retrospective study analyzed data from 2944 adult patients who underwent LDLT at 17 centers between 2016 and 2020. We developed a logistic regression model to predict EAD based on this development cohort. We used data from 1020 patients at the King Faisal Transplant Center for external validation. Results. In the development cohort, 321 patients (10.9%) experienced EAD. These patients had poorer health status, more liver decompensation, and higher requirements of hospitalization than those without EAD. Multivariable logistic regression identified independent pretransplant predictors of EAD: laboratory Model for End-Stage Liver Disease score (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.06-1.09), the necessity for hospitalization at the time of transplant (OR, 2.58; 95% CI, 2.00-3.30), and graft weight in kilogram (OR, 0.27; 95% CI, 0.17-0.45). Using these predictors, we developed the model for EAD after LDLT, which demonstrated strong discriminative ability in the development cohort with an area under the curve (AUC) of 0.71 (95% CI, 0.68-0.74). The model maintained high discrimination during internal validation (AUC, 0.70; 95% CI, 0.67-0.73) and showed a modest reduction in discriminative power in external validation (AUC, 0.65; 95% CI, 0.61-0.68). Conclusions. EAD post-LDLT is influenced by the recipient’s pretransplant health condition and the graft weight. Integrating the model for EAD after LDLT into the pretransplant process of pairing donors and recipients can enhance the safety and efficacy of LDLT.

There is a paucity of data on the impact of cold ischemia time before the initiation of normothermic machine perfusion (NMP), particularly in more susceptible organs such as livers from donation after circulatory death (DCD) donors. The present analysis aimed to investigate the impact of prolonged time from cross-clamp until NMP start on early allograft dysfunction and other peri–liver transplant (LT) outcomes. All DCD LT performed and placed on NMP at Mayo Clinic Arizona, Florida, and Rochester from January 2022 to March 2024 were included. The decision was made a priori to divide the population into 2 groups based on terciles: typical cross-clamp to on-pump time (lower 2 terciles) versus prolonged cross-clamp to on-pump time (upper tercile; >2 h 45.6 min). Three hundred eighty-four DCD LT undergoing NMP met the inclusion criteria. The rate of early allograft dysfunction was significantly higher in the prolonged cross-clamp to on-pump group (51.2%) compared to the typical cross-clamp to on-pump group (37.6%) (p = 0.01). The prolonged cross-clamp to on-pump group also had higher rates of acute kidney injury and the number of packed red blood cells transfused during LT. No significant difference in ischemic cholangiopathy (2.4% vs. 3.1%; p = 0.68) or graft survival at 12 months was seen between the prolonged cross-clamp to on-pump and typical cross-clamp to on-pump group, respectively. Following cross-clamp, DCD liver grafts should be placed on the NMP pump as quickly as is safely and logistically possible. In cases where delays are unavoidable, such as waiting for biopsy results or liver reallocation with another center, acceptable results can still be achieved, and therefore, livers with prolonged times should still be used.

With longer survival of patients with primary sclerosing cholangitis (PSC) undergoing liver transplantation (LT), the frequency and risk factors associated with vascular and biliary complications in the allograft and the impact on long-term outcomes are poorly understood. To assess frequency and risk factors for long-term outcomes in patients after LT for PSC, all recipients of LT for advanced stage PSC for a non-cholangiocarcinoma indication from 1984 to 2012, with follow-up through March 2022 (>10+ y follow-up), were identified. One-, 5-, and 10-year cumulative risks of complications were estimated using the Aalen-Johansen method, where death was considered a competing risk. Two hundred ninety-three patients (mean age, 47.3 ± 12 y) formed our study cohort. One hundred and thirty-four patients received LT before 1995, and 159 were transplanted after 1995. Over a median (IQR) follow-up of 15.0 (10.3–22.1) years, LT was complicated by hepatic artery thrombosis (N = 30), portal vein stenosis/thrombosis (N = 48), biliary leak (N = 47), biliary strictures (N = 87), recurrent PSC (N=107), and graft failure (N=70). The 1-, 5-, 10-, and 15-year cumulative incidence of recurrent PSC was 1.0%, 8.0%, 23.5%, and 34.3%, respectively. The type of donor and older donor age were associated with an increased risk of biliary strictures. Donor age >60 years was associated with an increased risk of recurrent PSC. Long-term patient and graft survival have not changed significantly for patients transplanted for PSC. Controlling transplant-related factors, such as donor age, prompt identification of vascular and biliary complications early, and long-term rigorous follow-up, is recommended to continue to improve on these outcomes.

ABSTRACT Background and Objectives Hepatic epithelioid hemangioendothelioma (HEHE) is an uncommon vascular neoplasm characterized by variable clinical behavior. Our aim was to describe the therapeutic approach for HEHE at diagnosis and define clinicopathological characteristics associated with tumor progression and long‐term survival. Methods This is a retrospective study that includes patients with HEHE who received treatment at Mayo Clinic Rochester between 1984 and 2023. Results Eighty patients were included in the study (median age: 44 years; 62.5% female), 24 underwent liver transplantation, 26 underwent liver resection, and 30 were managed medically. The 3‐year overall survival rates were 86.7%, 80.9%, and 51.1%, respectively. Notably, 26 patients had extrahepatic metastases at the time of diagnosis, four (16.7%) in the transplantation group, four (15.4%) in the resection group, and 18 (69.2%) in the nonsurgical group. On multivariable modeling, bone metastasis was independently associated with long‐term mortality (HR 6.3, p < 0.001) while lung metastasis and surgical intervention were not associated with long‐term mortality (HR 0.8, p = 0.8; HR 1.1, p = 0.9, respectively). Conclusion Bone metastasis emerged as a strong predictor of poor survival. Hence, aggressive surgical intervention may not be advantageous in patients with skeletal metastases but can still be offered for those with other extrahepatic metastases.

Objectives: Determine whether the timing of transplantation affects patient mortality. Background: Neoadjuvant therapy and liver transplantation have emerged as an excellent treatment option for select patients with perihilar cholangiocarcinoma (pCCA). However, the optimal timing of transplantation is not known. Methods: We reviewed all patients registered for a standardized pCCA protocol between 1996 and 2020 at our center. After adjusting for confounders, we examined the association of waiting time with patient mortality in an intention-to-treat cohort (n=392) and those who received a liver transplant (n=256). Results: The median (interquartile range) time from registration to transplant or dropout was 5.74 (3.25–7.06) months. Compared with a short wait time (0–3 mo), longer waiting times did not affect all-cause mortality: (3–6 mo) hazard ratio (HR) 0.98; 95% CI: 0.52–1.84; (6–9 mo) HR: 0.80; 95% CI: 0.39–1.65; (9–12 mo) HR: 0.56; 95% CI: 0.26–1.22. Subgroups with a shorter waiting time had similar survival to those with long waiting times: living donor available HR: 0.97; 95% CI: 0.67–1.42; AB or B blood group HR: 0.93; 95% CI: 0.62–1.39. Longer waiting times were associated with decreased all-cause mortality after transplantation (HR: 0.92; 95% CI: 0.87–0.97). This benefit began after a 6-month waiting time minimum (HR: 0.53; 95% CI: 0.26–1.10) and increased further after 9 months (HR: 0.43 95% CI: 0.20–0.93). Waiting time was not associated with residual adenocarcinoma in the explant (odds ratio 0.99; 95% CI: 0.98–1.00). Conclusions: A waiting time of at least 6 months will optimize results with transplantation without affecting overall (intention-to-treat) patient survival.

Background: The obesity epidemic has led to an increase in the proportion of patients with chronic liver disease due to metabolic associated steatosic liver disease and in the prevalence of obesity in patients with cirrhosis. Metabolic and bariatric surgery (MBS) has been proven to determine weight loss, obesity-related medical problems remission, and liver steatosis, inflammation, and fibrosis improvement. However, cirrhosis and portal hypertension are well-known risk factors for increased morbidity and mortality after surgery. The aim of this study is to evaluate the safety of MBS in patients with compensated advanced chronic liver disease (cALCD) and clinically significant portal hypertension (CSPH). Material and methods: This is an international, multicentric, retrospective study on 63 individuals affected by obesity with cALCD and CSPH who underwent MBS in tertiary referral centers with experts hepatobiliary surgeons between January 2010 and October 2022. The primary endpoint was postoperative mortality at 90 days. The secondary endpoints included postoperative weight loss at last follow-up and postoperative complication rate. In addition, the authors performed subgroup analyses of Child-Pugh (A vs. B) score, MELD (≤9 vs. >9) score, and type of surgery. Results: One patient (1.6%) experienced gastric leakage and mortality. There were three (5%) reported cases of portal vein thrombosis, two (3%) postoperative acute renal failure, and one (1.6%) postoperative encephalopathy. Child-Pugh score A resulted to be a protective factor for intraoperative bleeding requiring transfusion at univariate analysis (OR: 0.73, 95% CI: 0.55–0.97, P=0.046) but not at multivariate analysis. MELD>9 score and the type of surgery did not result to be a risk factor for any postoperative complication. Conclusion: MBS is safe in patients with cALCD and CSPH performed in tertiary bariatric referral centers with hepatobiliary expert surgeons. Larger, prospective studies with longer follow-up periods are needed to confirm these results.

Objective: To evaluate long-term oncologic outcomes of patients post–living donor liver transplantation (LDLT) within and outside standard transplantation selection criteria and the added value of the incorporation of the New York-California (NYCA) score. Background: LDLT offers an opportunity to decrease the liver transplantation waitlist, reduce waitlist mortality, and expand selection criteria for patients with hepatocellular carcinoma (HCC). Methods: Primary adult LDLT recipients between October 1999 and August 2019 were identified from a multicenter cohort of 12 North American centers. Posttransplantation and recurrence-free survival were evaluated using the Kaplan-Meier method. Results: Three hundred sixty LDLTs were identified. Patients within Milan criteria (MC) at transplantation had a 1, 5, and 10-year posttransplantation survival of 90.9%, 78.5%, and 64.1% versus outside MC 90.4%, 68.6%, and 57.7% (P = 0.20), respectively. For patients within the University of California San Francisco (UCSF) criteria, respective posttransplantation survival was 90.6%, 77.8%, and 65.0%, versus outside UCSF 92.1%, 63.8%, and 45.8% (P = 0.08). Fifty-three (83%) patients classified as outside MC at transplantation would have been classified as either low or acceptable risk with the NYCA score. These patients had a 5-year overall survival of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplantation would have been classified as a low or acceptable risk with a 5-year overall survival of 65.3%. Conclusions: Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-year rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria.

Objective: To define benchmark values for adult-to-adult living-donor liver transplantation (LDLT). Background: LDLT utilizes living-donor hemiliver grafts to expand the donor pool and reduce waitlist mortality. Although references have been established for donor hepatectomy, no such information exists for recipients to enable conclusive quality and comparative assessments. Methods: Patients undergoing LDLT were analyzed in 15 high-volume centers (≥10 cases/year) from 3 continents over 5 years (2016–2020), with a minimum follow-up of 1 year. Benchmark criteria included a Model for End-stage Liver Disease ≤20, no portal vein thrombosis, no previous major abdominal surgery, no renal replacement therapy, no acute liver failure, and no intensive care unit admission. Benchmark cutoffs were derived from the 75th percentile of all centers’ medians. Results: Of 3636 patients, 1864 (51%) qualified as benchmark cases. Benchmark cutoffs, including posttransplant dialysis (≤4%), primary nonfunction (≤0.9%), nonanastomotic strictures (≤0.2%), graft loss (≤7.7%), and redo-liver transplantation (LT) (≤3.6%), at 1-year were below the deceased donor LT benchmarks. Bile leak (≤12.4%), hepatic artery thrombosis (≤5.1%), and Comprehensive Complication Index (CCI ® ) (≤56) were above the deceased donor LT benchmarks, whereas mortality (≤9.1%) was comparable. The right hemiliver graft, compared with the left, was associated with a lower CCI ® score (34 vs 21, P < 0.001). Preservation of the middle hepatic vein with the right hemiliver graft had no impact neither on the recipient nor on the donor outcome. Asian centers outperformed other centers with CCI ® score (21 vs 47, P < 0.001), graft loss (3.0% vs 6.5%, P = 0.002), and redo-LT rates (1.0% vs 2.5%, P = 0.029). In contrast, non-benchmark low-volume centers displayed inferior outcomes, such as bile leak (15.2%), hepatic artery thrombosis (15.2%), or redo-LT (6.5%). Conclusions: Benchmark LDLT offers a valuable alternative to reduce waitlist mortality. Exchange of expertise, public awareness, and centralization policy are, however, mandatory to achieve benchmark outcomes worldwide.