Faculty Bibliography

BACKGROUND:Understanding factors that contribute to liver discards and nonusage is urgently needed to improve organ utilization. METHODS:Using Scientific Registry of Transplant Recipient data, we studied a national cohort of all US adult, deceased brain dead donor, isolated livers available for transplantation from 2003 to 2016, including organ-specific and system-wide factors that may affect organ procurement and discard rates. RESULTS:Of 73 686 available livers, 65 316 (88.64%) were recovered for transplant, of which 6454 (9.88%) were ultimately discarded. Livers that were not procured or, on recovery, discarded were more frequently from older, heavier, hepatitis B virus (HCV)+, and more comorbid donors (P < 0.001). However, even after adjustment for organ quality, the odds of liver nonusage were 11% higher on the weekend (defined as donor procurements with cross-clamping occurring from 5:00 PM Friday until 11:59 AM Sunday) compared with weekdays (P < 0.001). Nonuse rates were also higher at night (P < 0.001), defined as donor procurements with cross-clamping occurring from 5:00 PM to 5:00 AM; however, weekend nights had significantly higher nonuse rates compared with weekday nights (P = 0.005). After Share 35, weekend nonusage rates decreased from 21.77% to 19.51% but were still higher than weekday nonusage rates (P = 0.065). Weekend liver nonusage was higher in all 11 United Network of Organ Sharing regions, with an absolute average of 2.00% fewer available livers being used on the weekend compared with weekdays. CONCLUSIONS:Although unused livers frequently have unfavorable donor characteristics, there are also systemic and operational factors, including time of day and day of the week a liver becomes available, that impact the chance of liver nonprocurement and discard.

PURPOSE OF REVIEW:The aim of this review is to discuss existing data on liver transplantation for colorectal liver metastasis, emerging controversies, and future directions. RECENT FINDINGS:Contemporary experience with transplanting patients with liver metastasis from colon cancer is mainly derived from European centers, with a large proportion being from a single institution (SECA study), made possible in part by a relatively high donor pool. The initial results prove to be encouraging by demonstrating an overall survival advantage over unresectable patients with liver-limited disease managed with chemotherapy only. Recurrence patterns, however, suggest a need for better patient selection and treatment sequencing optimization. In North America, the main barriers in establishing similar protocols result from national liver graft shortage, which represents an issue of competing resources when indications have yet to be well defined. Evolving strategies in transplantation, such as the utilization of marginal liver grafts and living donor liver transplantation might constitute potential solutions. SUMMARY:Evidence suggests a potential survival benefit of liver transplantation for a subset of patients with unresectable liver-limited CRLM. Further prospective trials are needed to clarify the role and feasibility of this treatment strategy in oncotransplantation.

OBJECTIVE:The aim of this study was to assess improvements in long-term survival after liver transplant by analyzing outcomes in transplant recipients who survived beyond 1 year. SUMMARY OF BACKGROUND DATA:Gains in short-term survival following liver transplantation have been gratifying. One-year survival in 1986 was 66% improved to over 92% in 2015. However, little is known about why long-term has not seen similar success. METHODS:We analyzed 111,568 recipients from 1987 to 2016 using the Kaplan-Meier method for time-to-event analysis and multivariable Cox regression. RESULTS:There were no significant gains in unadjusted long-term outcomes among 1-year survivors over the past 30 years. Only the time periods of 1987 to 1990 [hazard ratio (HR) 1.35, confidence interval CI) 1.28-1.42] and 1991 to 1995 (HR 1.17, CI 1.13-1.21) had a minor increase in risk compared with the period 2011 to 2016. Cause of death analysis suggests malignancy after transplantation is a growing problem and preventing recurrent hepatitis C with direct-acting antivirals (DDAs) may only have a limited impact. Furthermore, rejection leading to graft failure and death had a rare occurrence (1.7% of long-term deaths) especially when compared with the sequelae of long-term immunosuppression: malignancy (16.4%), nonrejection graft failure (9.8%), and infection (10.5%) (P < 0.001). CONCLUSION:In stark contrast to short-term survival, there have been no appreciable improvements in long-term survival following liver transplantation among 1-year survivors. Long-term sequelae of immunosuppression, including malignancy and infection, are the most common causes of death. This study highlights the need for better long-term immunosuppression management.

OBJECTIVE:In order to minimize the impact of donation, fully laparoscopic donor hepatectomy (LDH) is being investigated at a few centers throughout the world. We report here our experience with 51 living donor pure laparoscopic hepatectomies. BACKGROUND:Adoption of minimal access techniques to living donor liver transplantation (LDLT) has been slowed by concerns about donor safety and the quality of the grafts. METHODS:Of 344 donor hepatectomies (DHs) for living donor liver transplantation (LDLT) since 1998, 51 pure LDH have been performed since 2009. We report here our experience with 51 living donor pure laparoscopic hepatectomy (LH), based on prospectively collected data. There were 31 left lateral sectionectomy and 20 full lobectomies LH. We matched full lobe LH to open DH prior to introduction of LH. RESULTS:LH increased from 21% of all DH in first 5 years of performing LH to 45% of DH in the most recent 3 years. Laparoscopic donors were more likely female, had lower body mass index, smaller total livers, and smaller allografts but longer operating room times. In the total LD experience, total 5 donors were converted to open surgery (10%), 2 donors required transfusion (4%), and there was 2 donor bile leaks (4%). Recipient patient and graft 1-year survival was 98% and 94%. CONCLUSIONS:Our experience indicates that LDH for LDLT can be safely used with appropriate attention to learning curve and progression from left lateral sectionectomy to right hepatectomy.

OBJECTIVES:European liver transplant (LT) centers have moved away from using the Milan Criteria (MC) for hepatocellular carcinoma (HCC) patient selection, turning to models including tumor biological indices, namely alpha-fetoprotein (AFP). We present the first US model to incorporate an AFP response (AFP-R), with comparisons to MC and French-AFP models (F-AFP). METHODS:AFP-R was measured as differences between maximum and final pre-LT AFP in HCC patients undergoing LT at 3 US centers (2001 to 2013). Cox and competing risk-regression analyses identified predictors of recurrence-free survival (RFS). RESULTS:Of 1450 patients, 235 (16.2%) were outside MC. Tumor size, number, and AFP-R were independent predictors of RFS and were assigned weighted points based on Cox-regression analysis. An AFP-R consistently < 200 ng/mL predicted the best outcome. A 3-tiered competing-risk RFS model, the New York/California (NYCA) score, was developed, accurately discriminating between groups (P < 0.001), and correlating with overall survival (P < 0.001). Two hundred one of 235 patients outside MC (85.5%) would be recategorized into NYCA low/acceptable-risk groups. The c-statistic for our NYCA score is 0.731 compared with 0.613 for MC and 0.658 for F-AFP (P < 0.0001). CONCLUSION:Incorporation of AFP-R into HCC selection criteria allows for MC expansion. As United Network for Organ Sharing considers adding AFP to selection algorithms, the NYCA score provides an objective, user-friendly tool for centers to appropriately risk-stratify patients.

BACKGROUND:An index that predicts liver allograft discard can effectively grade allografts and can be used to preferentially allocate marginal allografts to aggressive centers. The aim of this study is to devise an index to predict liver allograft discard using only risk factors available at the time of initial DonorNet offer. METHODS:Using univariate and multivariate analyses on a training set of 72 297 deceased donors, we identified independent risk factors for liver allograft discard. Multiple imputation was used to account for missing variables. RESULTS:We identified 15 factors as significant predictors of liver allograft discard; the most significant risk factors were: total bilirubin > 10 mg/dL (odds ratio [OR], 25.23; confidence interval [CI], 17.32-36.77), donation after circulatory death (OR, 14.13; CI, 13.30-15.01), and total bilirubin 5 to 10 mg/dL (OR, 7.57; 95% CI, 6.32-9.05). The resulting Discard Risk Index (DSRI) accurately predicted the risk of liver discard with a C statistic of 0.80. We internally validated the model with a validation set of 37 243 deceased donors and also achieved a 0.80 C statistic. At a DSRI at the 90th percentile, the discard rate was 50% (OR, 32.34; CI, 28.63-36.53), whereas at a DSRI at 10th percentile, only 3% of livers were discarded. CONCLUSIONS:The use of the DSRI can help predict liver allograft discard. The DSRI can be used to effectively grade allografts and preferentially allocate marginal allografts to aggressive centers to maximize the donor yield and expedite allocation.

Of the 1.6 million patients >70 years of age who died of stroke since 2002, donor livers were retrieved from only 2402 (0.15% yield rate). Despite reports of successful liver transplantation (LT) with elderly grafts (EG), advanced donor age is considered a risk for poor outcomes. Centers for Medicare and Medicaid Services definitions of an "eligible death" for donation excludes patients >70 years of age, creating disincentives to donation. We investigated utilization and outcomes of recipients of donors >70 through analysis of a United Network for Organ Sharing Standard Transplant Analysis and Research-file of adult LTs from 2002 to 2014. Survival analysis was conducted using Kaplan-Meier curves, and Cox regression was used to identify factors influencing outcomes of EG recipients. Three thousand one hundred four livers from donors >70, ≈40% of which were used in 2 regions: 2 (520/3104) and 9 (666/3104). Unadjusted survival was significantly worse among recipients of EG compared to recipients of younger grafts (P < .0001). Eight independent negative predictors of survival in recipients of EG were identified on multivariable analysis. Survival of low-risk recipients who received EG was significantly better than survival of recipients of younger grafts (P = .04). Outcomes of recipients of EG can therefore be optimized to equal outcomes of younger grafts. Given the large number of stroke deaths in patients >70 years of age, the yield rate of EGs can be maximized and disincentives removed to help resolve the organ shortage crisis.