Transplanting hepatitis B surface antigen-positive livers in the United States: Outcomes and opportunities.

Livers from donors with positive hepatitis B surface antigens (HBsAg+) have been used to expand the donor pool; however, outcome data are limited. We aim to evaluate survival following liver transplant (LT) from HBsAg+ donors. Using the United Network for Organ Sharing registry, we identified HBsAg+ donors used for LT from 2009 to 2020. We used Kaplan-Meier survival and Cox proportional hazards regression to compare post-LT survival in hepatitis B virus-negative recipients who utilized HBsAg+ donors to propensity-matched cohorts who utilized other types of donors. From 2009-2020, 70 patients received HBsAg+ livers, and 58 of them did not carry a diagnosis of chronic hepatitis B virus. The 1- and 3-year post-LT survival for hepatitis B virus-negative patients who received livers from HBsAg+ donors were 96.6% and 91.4%, respectively, with no statistical differences compared with patients who received livers from hepatitis C virus viremic donors (96.5%/93.0%, P = .961/.427), donation after cardiac death donors (93.0%/86.0%, P = .651/.598), average-risk donors (89.5%/86.0%, P = 0.264/0.617), and a combination of extended-criteria donors, including donation after cardiac death, donor age over 70, and graft with greater than 30% steatosis (93.0%/91.2%, P = .621/.785). Recipients of HBsAg+ livers have similar post-LT survival compared with those receiving other types of grafts. Increasing the utilization of HBsAg+ livers could safely expand the donor pool.

Human wastewater tracking in tropical Hawaiian island streams using qualitative and quantitative assessments of combined fecal indicating bacteria and sucralose, an organic micropollutant of emerging concern.

Prevalence of cesspools on tropical islands suggests that high concentrations of enteric bacteria in streams and coastal waters are an indicator of groundwater contamination by human wastewater. But enterococci bacteria may also be from homeothermic animals common to these watersheds or bacteria living in sediments. Sucralose, a manufactured chemical not destroyed in passage through the human gut, cesspools, septic systems, or wastewater treatment facilities, was used to test for the presence of human wastewater in streams on the island of Kauai, Hawaii. Effluent from six municipal wastewater treatment plants showed an average concentration of 39,167 ng/L of sucralose, roughly back-calculated to 9 ng/L per person, enough to present itself in cesspool effluent contaminated waters. Of 24 streams tested, 79% were positive for sucralose at least once in four sets of sampling. All streams tested positive for enterococci bacteria above established standards. Serial testing of the pair of indicators in the same location over time and applying the Multiplication Rule to the independent samples provide a probabilistic certainty level that the water is chronically polluted by human waste. When repeatedly paired with tests for enterococci, sucralose testing is a cost-effective means for assessing human health risk and for developing proper waste management programs that has been underutilized in under-developed tropical and island settings.

LR-3 and LR-4 Lesions Are More Likely to Be Hepatocellular Carcinoma in Transplant Patients with LR-5 or LR-TR Lesions.

BACKGROUND: Liver Imaging Reporting and Data System (LI-RADS) classifies liver nodules from LR-1 to LR-5 based on risk for hepatocellular carcinoma (HCC). It is challenging to know the nature of the LR-3 and LR-4 lesions. AIMS: To test our hypothesis that in patients with a definite HCC (LR-5) or treated HCC (LR-TR), a coexisting LR-3 or LR-4 lesion is more likely to represent HCC compared to patients without LR-5 or LR-TR lesions. METHODS: We conducted a retrospective study including all adult patients who received liver transplantation in our institution from 1/1/2014 to 3/3/2020 who had any LR-3 or LR-4 lesion on pre-transplant MRI. RESULTS: Seventy-eight patients were included in the final cohort (115 LR-3 and LR-4 lesions total). When accompanied by LR-5 or LR-TR lesions, 41% (28/69) of LR-3 lesions were HCC compared to 12% (3/25) when not accompanied by LR-5 LR-TR lesions. When accompanied by LR-5 or LR-TR lesions, 83% (10/12) of LR-4 lesions were HCC, versus 33% (3/9) when not accompanied by LR-5 or LR-TR lesions. In a multivariable analysis of all lesions, the presence of a LR-5 or LR-TR lesion was significantly associated with LR-3 or LR-4 lesions representing HCC (OR 6.4, p = 0.01). CONCLUSION: LR-3 and LR-4 lesions are more likely to be HCC in patients with LR-5 or LR-TR lesions. The presence of coexisting definite HCC may be a useful diagnostic feature to improve risk stratification of lesions without typical imaging features of HCC. This may also affect decision-making prior to liver transplant when HCC burden must be accurately determined.

The Impact of the 2017 Kidney Allocation Policy Change on Simultaneous Liver-Kidney Utilization and Outcomes.

Historically in the United States, kidneys for simultaneous liver-kidney transplantation (SLKT) candidates were allocated with livers, prioritizing SLKT recipients over much of the kidney waiting list. A 2017 change in policy delineated renal function criteria for SLKT and implemented a safety net for kidney-after-liver transplantation. We compared the use and outcomes of SLKT and kidney-after-liver transplant with the 2017 policy. United Network for Organ Sharing Standard Transplant Analysis and Research files were used to identify adults who received liver transplantations (LT) from August 10, 2007 to August 10, 2012; from August 11, 2012 to August 10, 2017; and from August 11, 2017 to June 12, 2019. LT recipients with end-stage renal disease (ESRD) were defined by dialysis requirement or estimated glomerular filtration rate <25. We evaluated outcomes and center-level, regional, and national practice before and after the policy change. Nonparametric cumulative incidence of kidney-after-liver listing and transplant were modeled by era. A total of 6332 patients received SLKTs during the study period; fewer patients with glomerular filtration rate (GFR) ≥50 mL/min underwent SLKT over time (5.8%, 4.8%, 3.0%; P = 0.01 ). There was also less variability in GFR at transplant after policy implementation on center and regional levels. We then evaluated LT-alone (LTA) recipients with ESRD (n = 5408 from 2012-2017; n = 2321 after the policy). Listing for a kidney within a year of LT increased from 2.9% before the policy change to 8.8% after the policy change, and the rate of kidney transplantation within 1 year increased from 0.7% to 4% (P < 0.001). After the policy change, there was no difference in patient survival rates between SLKT and LTA among patients with ESRD. Implementation of the 2017 SLKT policy change resulted in reduced variability in SLKT recipient kidney function and increased access to deceased donor kidney transplantation for LTA recipients with kidney disease without negatively affecting outcomes.

Regional and global perspectives of honey as a record of lead in the environment.

Honey from Apis mellifera is a useful and inexpensive biomonitor for mapping metal distributions in urban centers. The sampling resolution of a biomonitoring survey (e.g., city versus global scale) determines which geochemical processes are reflected in the results. This study presents Pb isotopic compositions and metal concentrations in honey from around the world, sampled at varying resolutions: honey from Canada (n = 21), the United States (n = 111), Belgium (n = 25), and New Zealand (n = 10), with additional samples from Afghanistan, Brazil, Cuba, Germany, Liberia, Taiwan, and Turkey. Honey was sampled at high resolution in two uniquely different land-use settings (New York Metro Area and the Hawaiian island of Kaua'i), at regional-scale resolution in eastern North America (including the Great Lakes region), and Pb isotopic compositions of all samples were compared on a global scale. At high sampling resolution, metal concentrations in honey reveal spatially significant concentration gradients: in New York City, metals associated with human activity and city infrastructure (e.g., Pb, Sb, Ti, V) are more concentrated in honey collected within the city compared to honey from upstate New York, and metal concentrations in honey from Kaua'i suggest polluting effects of nearby agricultural operations. At lower resolution (regional and global scales), lead isotopic compositions of honey are more useful than metal concentrations in revealing large-scale Pb processes (e.g., the enduring legacy of global leaded gasoline use throughout the twentieth century) and the continental origin of the honey. Lead isotopic compositions of honey collected from N. America (especially from the eastern USA) are more radiogenic (206Pb/207Pb: 1.132-1.253, 208Pb/206Pb: 2.001-2.129) compared to European honey, and honey from New Zealand, which has the least radiogenic isotopic compositions measured in this study (206Pb/207Pb: 1.077-1.160, 208Pb/206Pb: 2.090-2.187). Thus, biomonitoring using honey at different resolutions reflects differing processes and, to some extent, a honey terroir defined by the Pb isotopic composition. The data presented here provide important (and current) global context for future studies that utilize Pb isotopes in honey. Moreover, this study exhibits community science in action, as most of the honey was collected by collaborators around the world, working directly with local apiarists and hobby beekeepers.

Left lateral segment liver volume is not correlated with anthropometric measures.

BACKGROUND: Liver transplantation is definitive therapy for end stage liver disease in pediatric patients. Living donor liver transplantation (LDLT) with the left lateral segment (LLS) is often a feasible option. However, the size of LLS is an important factor in donor suitability - particularly when the recipient weighs less than 10 kg. In the present study, we sought to define a formula for estimating left lateral segment volume (LLSV) in potential LLS donors. METHODS: We obtained demographic and anthropometric measurements on 50 patients with Computed Tomography (CT) scans to determine whole liver volume (WLV), right liver volume (RLV), and LLSV. We performed univariable and multivariable linear regression with backwards stepwise variable selection (p < 0.10) to determine final models. RESULTS: Our study found that previously reported anthropometric and demographics variables correlated with volume were significantly associated with WLV and RLV. On univariable analysis, no demographic or anthropometric measures were correlated with LLSV. On multivariable analysis, LLSV was poorly predicted by the final model (R2 = 0.10, Coefficient of Variation [CV] = 42.2) relative to WLV (R2 = 0.33, CV = 18.8) and RLV (R2 = 0.41, CV = 15.8). CONCLUSION: Potential LLS living donors should not be excluded based on anthropometric data: all potential donors should be evaluated regardless of their size.

Textbook Outcomes in Liver Transplantation.

BACKGROUND: Textbook outcome (TO) is an emerging concept within multiple surgical domains, which represents a novel effort to define a standardized, composite quality benchmark based on multiple postoperative endpoints that represent the ideal "textbook" hospitalization. We sought to define TO for liver transplantation (LT) using a cohort from a high procedural volume center. METHODS: Patients who underwent LT at our institution between 2014 and 2017 were eligible for the study. The definition of TO was determined by clinician consensus at our institution to include freedom from: mortality within 90 days, primary allograft non-function, early allograft dysfunction (EAD), rejection within 30 days, readmission with 30 days, readmission to the ICU during index hospitalization, hospital length of stay > 75th percentile of all liver transplant patients, red blood cell (RBC) transfusion requirement greater than the 75th percentile for all liver transplant patients, Clavien-Dindo Grade III complication (re-intervention), and major intraoperative complication. RESULTS: Two hundred and thirty-one liver transplants with complete data were performed within the study period. Of those, 71 (31%) achieved a TO. Overall, the most likely event to lead to failure to achieve TO was readmission within 30 days (n = 57, 37%) or reoperation (n = 49, 32%). Overall and rejection-free survival did not differ significantly between the 2 groups. Interestingly, patients who achieved TO incurred approximately $60,000 less in total charges than those who did not. When we limit this to charges specifically attributable to the transplant episode, the difference was approximately $50,000 and remained significantly less for those that achieved TO. CONCLUSIONS: Here, we present the first definition of TO in LT. Though not associated with long-term outcomes, TO in LT is associated with a significantly lower charges and costs of the initial hospitalization. A multi-institutional study to validate this definition of TO is warranted.

Dysregulated activation of fetal liver programme in acute liver failure.

OBJECTIVE: Uncertainty about acute liver failure (ALF) pathogenesis limits therapy. We postulate that ALF results from excessive reactivation of a fetal liver programme that is induced in hepatocytes when acutely injured livers regenerate. To evaluate this hypothesis, we focused on two molecules with known oncofetal properties in the liver, Yes-associated protein-1 (YAP1) and Insulin-like growth factor-2 RNA-binding protein-3 (IGF2BP3). DESIGN: We compared normal liver with explanted livers of patients with ALF to determine if YAP1 and IGF2BP3 were induced; assessed whether these factors are upregulated when murine livers regenerate; determined if YAP1 and IGF2BP3 cooperate to activate the fetal programme in adult hepatocytes; and identified upstream signals that control these factors and thereby hepatocyte maturity during recovery from liver injury. RESULTS: Livers of patients with ALF were massively enriched with hepatocytes expressing IGF2BP3, YAP1 and other fetal markers. Less extensive, transient accumulation of similar fetal-like cells that were proliferative and capable of anchorage-independent growth occurred in mouse livers that were regenerating after acute injury. Fetal reprogramming of hepatocytes was YAP1-dependent and involved YAP1-driven reciprocal modulation of let7 microRNAs and IGF2BP3, factors that negatively regulate each other to control fate decisions in fetal cells. Directly manipulating IGF2BP3 expression controlled the fetal-like phenotype regardless of YAP1 activity, proving that IGF2BP3 is the proximal mediator of this YAP1-directed fate. CONCLUSION: After acute liver injury, hepatocytes are reprogrammed to fetal-like cells by a YAP1-dependent mechanism that differentially regulates let7 and IGF2BP3, identifying novel therapeutic targets for ALF.

The impact of human leukocyte antigen donor and recipient serotyping and matching on liver transplant graft failure in primary sclerosing cholangitis, autoimmune hepatitis, and primary biliary cholangitis.

Human leukocyte antigen (HLA) serotyping is not considered to have significant impact on liver graft survival and does not factor into U.S. organ allocation. Immune-related liver diseases such as primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), and primary biliary cholangitis (PBC) have been speculated to represent a disease subgroup that may have significantly different graft outcomes depending on HLA donor/recipient characterization. The aim of this study was to investigate whether HLA serotyping/matching influenced post-transplant graft failure for immune-related liver diseases using the United Network for Organ Sharing database. From 1994 to 2015, 5665 patients underwent first-time liver-only transplants for PSC, AIH, and PBC with complete graft survival and donor/recipient HLA data. Graft failure was noted in 38.6% (2188/5665), and all groups had comparable 5-year graft survival (75.1%-78.8%, P = 0.069). The overall degree of, and loci-specific mismatch level, did not influence outcomes. Multivariable Cox proportional hazards regression noted increased graft failure risk for recipient HLA-B7, HLA-B57, HLA-B75, HLA-DR13 and donor HLA-B55, HLA-B58, and HLA-DR8 for PSC patients, protective effects for recipient HLA-DR1 and HLA-DR3 for AIH patients, and increased risk for HLA-DR7 for AIH patients. These findings warrant further investigation to evaluate the impact of HLA serotyping on post-transplant outcomes.

Biliary reconstructive techniques and associated anatomic variants in adult living donor liver transplantations: The adult-to-adult living donor liver transplantation cohort study experience.

Living donor liver transplantation (LDLT) is a technically demanding endeavor, requiring command of the complex anatomy of partial liver grafts. We examined the influence of anatomic variation and reconstruction techniques on surgical outcomes and graft survival in the 9-center Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). Data from 272 adult LDLT recipients (2011-2015) included details on anatomic characteristics and types of intraoperative biliary reconstruction. Associations were tested between reconstruction technique and complications, which included first biliary complication (BC; leak, stricture, or biloma) and first vascular complication (VC; hepatic artery thrombosis [HAT] or portal vein thrombosis [PVT]). Time to patient death, graft failure, and complications were estimated using Kaplan-Meier curves and tested with log-rank tests. Median posttransplant follow-up was 1.2 years. Associations were found between the type of biliary reconstruction and the incidence of VC (P = 0.03) and BC (P = 0.05). Recipients with Roux-en-Y hepaticojejunostomy had the highest probability of VC. Recipients with biliary reconstruction involving the use of high biliary radicals on the recipient duct had the highest likelihood of developing BC (56% by 1 year) compared with duct-to-duct (42% by 1 year). In conclusion, the varied surgical approaches in the A2ALL centers offer a novel opportunity to compare disparate LDLT approaches. The choice to use higher biliary radicals on the recipient duct for reconstruction was associated with more BC, possibly secondary to devascularization and ischemia. The use of Roux-en-Y biliary reconstruction was associated with VCs (HAT and PVT). These results can be used to guide biliary reconstruction decisions in the setting of anatomic variants and inform further improvements in LDLT reconstructions. Ultimately, this information may contribute to a lower incidence of technical complications after LDLT. Liver Transplantation 23 1519-1530 2017 AASLD.

Excess mortality on the liver transplant waiting list: unintended policy consequences and Model for End-Stage Liver Disease (MELD) inflation.

UNLABELLED: The Model for End-Stage Liver Disease (MELD) allocation system for liver transplantation provides "exceptions" for diseases such as hepatocellular carcinoma (HCC). It was the aim of this study to assess equipoise between exception candidates and nonexception candidates on the waiting list and to assess if the exception system contributes to steadily increasing regional MELD at transplant. In all, 78,595 adult liver transplant candidates between January 2005 and December 2012 were analyzed. Yearly trends in waiting list characteristics and transplantation rates were analyzed for statistical association with MELD exceptions. Regional variations in these associations and the effect of exceptions on regional MELD scores at transplant were also analyzed. 27.29% of the waiting list was occupied by candidates with exceptions. Candidates with exceptions fared much better on the waiting list compared to those without exceptions in mean days waiting (HCC 237 versus non-HCC 426), transplantation rates (HCC 79.05% versus non-HCC 40.60%), and waiting list death rates (HCC 4.49% versus non-HCC 24.63%). Strong regional variation in exception use occurred but exceptions were highly correlated with waiting list death rates, transplantation rates, and MELD score at removal in all regions. In a multivariate model predicting MELD score at transplant within regions, the percentage of HCC MELD exceptions was the strongest independent predictor of regional MELD score at transplant. CONCLUSION: Liver transplant candidates with MELD exceptions have superior outcomes compared to nonexception candidates and the current MELD exception system is largely responsible for steadily increasing MELD scores at transplant independent of geography.

How reader perception of capsule affects interpretation of washout in hypervascular liver nodules in patients at risk for hepatocellular carcinoma.

PURPOSE: To determine whether reader perception of a capsule affects reader interpretation of washout in hypervascular liver nodules at dynamic magnetic resonance imaging (MRI) in patients at risk for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study was Institutional Review Board (IRB)-approved and Health Insurance Portability and Accountability Act (HIPAA)-compliant, with waiver of informed consent. MRI reports for 111 hypervascular liver nodules (median 2.0 cm, range 1.0-17.8 cm) in 62 patients were reviewed, and the presence/absence of capsule and washout were recorded for one reading. A second independent study reading was also performed. The signal intensity ratio (SIR) for each nodule and liver parenchyma was measured. An objective SIR threshold was identified for nodules without capsules that correctly classified the presence/absence of washout, then applied to nodules with capsules to classify them as having / not having objective washout. Nodules were categorized as definite / not definite HCC using subjective and objective washout, based on LI-RADS, OPTN, AASLD, and EASL criteria, and proportions compared using McNemar's test. RESULTS: Agreement on nodule features was high for Readings 1 and 2 (κ = 0.70-0.82). For Reading 1, 71 nodules lacked capsules (43 with and 28 without subjective washout); an SIR threshold of 0.88 classified the presence/absence of washout correctly in 94% (67/71, P < 0.001). Forty nodules had capsules; although all had subjective washout (100%, 40/40), 75% (30/40) had objective washout (P < 0.05). Using objective washout caused 4.5% (3/66; LI-RADS, OPTN) and 12% (10/83; AASLD, EASL) of nodules to be recategorized from definite HCC to not definite HCC. CONCLUSION: Reader perception of capsule affects interpretation of washout. This effect can influence nodule categorization using imaging-based diagnostic systems. J. Magn. Reson. Imaging 2016;43:1337-1345.

Effectiveness of Transarterial Embolization of Hepatocellular Carcinoma as a Bridge to Transplantation.

PURPOSE: To assess the effectiveness of bland transarterial embolization of hepatocellular carcinoma (HCC) as a "bridge" to transplantation. MATERIALS AND METHODS: In this retrospective study, 117 patients with HCC that met Milan criteria underwent bland embolization as their initial and sole therapy for treatment of HCC (88 men and 29 women; mean age, 60.4 y; range, 35-88 y). Subsequent postembolization contrast-enhanced computed tomography or magnetic resonance imaging studies were reviewed to determine whether Milan criteria were met in an intent-to-transplant analysis. Freedom from progression beyond Milan criteria and survival were calculated by Kaplan-Meier technique. Predictors of progression and survival were also assessed. RESULTS: After embolization, 87% and 78% of patients' disease still met Milan criteria at 6 and 12 months, respectively. The median time until disease progression beyond Milan criteria was 22.6 months (95% confidence interval, 16.2-29 mo). α-Fetoprotein levels, number of lesions, United Network for Organ Sharing stage, Model for End-stage Liver Disease score, and cirrhosis etiology did not correlate significantly with stability within Milan criteria. A total of 34 patients (29%) underwent eventual liver transplantation at a median of 3.3 months (range, 0.5-20.9 mo). Liver transplantation was a significant independent predictor of longer survival (6.9 y vs 2.6 y; P < .001). The major complication rate within 30 days of embolization was 2.6%, including one mortality. CONCLUSIONS: Bland transarterial embolization as a bridging strategy to maintain HCC within Milan criteria was successful in 78% of patients at 1 year, which compares favorably with other locoregional embolotherapies.

Nonalcoholic Fatty Liver Disease: Key Considerations Before and After Liver Transplantation.

Nonalcoholic fatty liver disease (NAFLD) is the most common etiology of chronic liver disease in developed countries and is on trajectory to become the leading indication for liver transplantation in the USA and much of the world. Patients with NAFLD cirrhosis awaiting liver transplant face unique challenges and increased risk for waiting list stagnation and dropout due to burdensome comorbidities including obesity, diabetes, cardiovascular disease, and kidney disease. Thus far, patients transplanted for NAFLD cirrhosis have excellent mid- and long-term patient and graft survival, but concerns regarding short-term morbidity and mortality continue to exist. Post-liver transplantation, NAFLD occurs as both a recurrent and de novo manifestation, each with unique outcomes. NAFLD in the donor population is of concern given the growing demand for liver transplantation and mounting pressure to expand the donor pool. This review addresses key issues surrounding NAFLD as an indication for transplantation, including its increasing prevalence, unique patient demographics, outcomes related to liver transplantation, development of post-liver transplantation NAFLD, and NAFLD in the liver donor population. It also highlights exciting areas where further research is needed, such as the role of bariatric surgery and preconditioning of marginal donor grafts.

Liver Transplantation in 2016: An Update.

Liver transplantation is a lifesaving intervention for patients with decompensated cirrhosis, certain malignancies, and genetic disorders associated with disordered liver metabolism. This commentary will discuss the indications for liver transplantation, the evaluation of liver transplant candidates, prioritization of candidates on the waiting list, and post-transplant care.

Long-term quality of life after liver donation in the adult to adult living donor liver transplantation cohort study (A2ALL).

BACKGROUND & AIMS: There are few long-term studies of the health-related quality of life (HRQOL) in living liver donors. This study aimed to characterize donor HRQOL in the Adult to Adult Living Donor Liver Transplantation Study (A2ALL) up to 11 years post-donation. METHODS: Between 2004 and 2013, HRQOL was assessed at evaluation, at 3 months, and yearly post-donation in prevalent liver donors using the short-form survey (SF-36), which provides a physical (PCS) and a mental component summary (MCS). RESULTS: Of the 458 donors enrolled in A2ALL, 374 (82%) had SF-36 data. Mean age at evaluation was 38 (range 18-63), 47% were male, 93% white, and 43% had a bachelor's degree or higher. MCS and PCS means were above the US population at all time points. However, at every time point there were some donors who reported poor scores (>1/2 standard deviation below the age and sex adjusted mean) (PCS: 5.3-26.8%, MCS: 10.0-25.0%). Predictors of poor PCS and MCS scores included recipient's death within the two years prior to the survey and education less than a bachelor's degree; poor PCS scores were also predicted by time since donation, Hispanic ethnicity, and at the 3-month post-donation time point. CONCLUSIONS: In summary, most living donors maintain above average HRQOL up to 11 years prospectively, supporting the notion that living donation does not negatively affect HRQOL. However, targeted support for donors at risk for poor HRQOL may improve overall HRQOL outcomes for living liver donors.

Defining long-term outcomes with living donor liver transplantation in North America.

OBJECTIVES: To compare long-term survival of living donor liver transplant (LDLT) at experienced transplant centers with outcomes of deceased donor liver transplant and identify key variables impacting patient and graft survival. BACKGROUND: The Adult-to-Adult Living Donor Liver Transplantation Cohort Study is a prospective multicenter National Institutes of Health study comparing outcomes of LDLT and deceased donor liver transplant and associated risks. METHODS: Mortality and graft failure for 1427 liver recipients (963 LDLT) enrolled in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study who received transplant between January 1, 1998, and January 31, 2014, at 12 North American centers with median follow-up 6.7 years were analyzed using Kaplan-Meier and multivariable Cox models. RESULTS: Survival probability at 10 years was 70% for LDLT and 64% for deceased donor liver transplant. Unadjusted survival was higher with LDLT (hazard ratio = 0.76, P = 0.02) but attenuated after adjustment (hazard ratio = 0.98, P = 0.90) as LDLT recipients had lower mean model for end-stage liver disease (15.5 vs 20.4) and fewer received transplant from intensive care unit, were inpatient, on dialysis, were ventilated, or with ascites. Posttransplant intensive care unit days were less for LDLT recipients. For all recipients, female sex and primary sclerosing cholangitis were associated with improved survival, whereas dialysis and older recipient/donor age were associated with worse survival. Higher model for end-stage liver disease score was associated with increased graft failure. Era of transplantation and type of donated lobe did not impact survival in LDLT. CONCLUSIONS: LDLT provides significant long-term transplant benefit, resulting in transplantation at a lower model for end-stage liver disease score, decreased death on waitlist, and excellent posttransplant outcomes. Recipient diagnosis, disease severity, renal failure, and ages of recipient and donor should be considered in decision making regarding timing of transplant and donor options.Clinical Trials ID: NCT00096733.