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Background & Aims Death rates on liver transplant waiting lists range from 5%–25%. Herein, we report a unique experience with 50 anonymous individuals who volunteered to address this gap by offering to donate part of their liver to a recipient with whom they had no biological connection or prior relationship, so called anonymous live liver donation (A-LLD). Methods Candidates were screened to confirm excellent physical, mental, social, and financial health. Demographics and surgical outcomes were analyzed. Qualitative interviews after donation examined motivation and experiences. Validated self-reported questionnaires assessed personality traits and psychological impact. Results A total of 50 A-LLD liver transplants were performed between 2005 and 2017. Most donors had a university education, a middle-class income, and a history of prior altruism. Half were women. Median age was 38.5 years (range 20–59). Thirty-three (70%) learned about this opportunity through public or social media. Saving a life, helping others, generativity, and reciprocity for past generosity were motivators. Social, financial, healthcare, and legal support in Canada were identified as facilitators. A-LLD identified most with the personality traits of agreeableness and conscientiousness. The median hospital stay was 6 days. One donor experienced a Dindo-Clavien Grade 3 complication that completely resolved. One-year recipient survival was 91% in 22 adults and 97% in 28 children. No A-LLD reported regretting their decision. Conclusions This is the first and only report of the characteristics, motivations and facilitators of A-LLD in a large cohort. With rigorous protocols, outcomes are excellent. A-LLD has significant potential to reduce the gap between transplant organ demand and availability. Lay summary We report a unique experience with 50 living donors who volunteered to donate to a recipient with whom they had no biological connection or prior relationship (anonymous living donors). This report is the first to discuss motivations, strategies and facilitators that may mitigate physical, social and ethical risk factors in this patient population. With rigorous protocols, anonymous liver donation and recipient outcomes are excellent; with appropriate clinical expertise and system facilitators in place, our experience suggests that other centers may consider the procedure for its significant potential to reduce the gap between transplant organ demand and availability.

Background Primary sclerosing cholangitis (PSC) is an indication for liver transplantation, but recurrence after liver transplantation is associated with poor outcomes often requiring repeat transplantation. We investigated whether autologous hematopoietic stem cell transplantation (aHSCT) could be used to stop progression of recurrent PSC and promote operational tolerance. Methods Twelve patients with recurrent PSC were fully evaluated and 5 were selected for aHSCT. Autologous hematopoietic stem cells were collected, purified by CD34 immunomagnetic selection and cryopreserved. Immunoablation using busulfan, cyclophosphamide and rabbit anti-thymocyte globulin was followed by aHSCT. The primary endpoint of the study was the establishment of operational tolerance defined as lack of biochemical, histologic and clinical evidence of rejection while off immunosuppression at 2 years post-aHSCT. Results Two of the 5 patients achieved operational tolerance with no clinical or histological evidence of PSC progression or allo-rejection. A third patient developed sinusoidal obstruction syndrome following aHSCT requiring repeat liver transplantation but has no evidence of PSC recurrence while on sirolimus monotherapy now more than 3 years after aHSCT. A fourth patient was weaned off immunosuppression but died 212 days after aHSCT from pericardial constriction. A fifth patient died from multiorgan failure. Immunosuppression-free allograft acceptance was associated with deletion of T cell clones, loss of autoantibodies and increases in regulatory T cells, transitional B cells, and programmed cell death protein-1 expressing CD8+ T cells in the 2 long-term survivors. Conclusions Although operational tolerance occurred following aHSCT, the high morbidity and mortality observed renders this specific protocol unsuitable for clinical adoption.

BACKGROUND There is a lack of information about survival after dropout from the liver transplant waiting list. Therefore, we aimed to assess the overall survival, and risk factors for death, after waiting list dropout due to hepatocellular carcinoma (HCC) progression. METHODS We assessed patients who dropped out of the liver transplant waiting list between 2000 and 2016 in a single, large academic North American center. Patients were divided into 3 groups according to the types of HCC progression: locally advanced disease (LAD), extrahepatic disease (EHD), and macrovascular invasion (MVI). The primary outcome was overall survival. Survival was assessed by the Kaplan-Meier method. Predictors of death after dropout were assessed by multivariable Cox regression. RESULTS During the study period, 172 patients dropped out due to HCC progression. Of those, 37 (21.5%), 74 (43%), and 61 (35.5%) dropped out due to LAD, EHD, and MVI, respectively. Median survival according to cause of dropout (LAD, EHD, or MVI) was 1.0, 4.4, or 3.3 months, respectively (P = 0.01). Model for End-stage Liver Disease (MELD) score (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.01-1.08), alcoholic liver disease (HR, 1.66; 95% CI, 1.02-2.71), and α-fetoprotein >1000 ng/mL (HR, 1.86; 95% CI, 1.22-2.84) were predictors of mortality after dropout. Dropout due to EHD (HR, 0.61; 95% CI, 0.38-0.98) and undergoing treatment after dropout were protective factors (HR, 0.32; 95% CI, 0.21-0.48) for death. CONCLUSIONS Patient prognosis after dropout is dismal. However, a subgroup of patients may have longer survival. The present study identifies the patterns of waitlist dropout in patients with HCC and provides evidence for the effectiveness of treatment strategies offered to HCC patients after dropout.

Radiofrequency ablation (RFA) is an effective treatment for single hepatocellular carcinoma (HCC) ≤3 cm. Disease recurrence is common, and in some patients will occur outside transplant criteria. We aimed to assess the incidence and risk factors for recurrence beyond Milan criteria in potentially transplantable patients treated with RFA as first-line therapy.We performed a retrospective cohort study of potentially transplantable patients with new diagnoses of unifocal HCC ≤3 cm that underwent RFA as first-line therapy between 2000-2015. We defined potentially transplantable patients as those aged70 years without any comorbidities that would preclude transplant surgery. Incidence of recurrence beyond Milan criteria was compared across 2 groups according to HCC diameter at the time of ablation: (HCC ≤2 cm vs. HCC2 cm). Competing risks Cox regression was used to identify predictors of recurrence beyond Milan criteria.We included 301 patients (167 HCC ≤2 cm and 134 HCC2 cm). Recurrence beyond Milan criteria occurred in 36 (21.6%) and 47 (35.1%) patients in the HCC ≤2 cm and the HCC2 cm groups, respectively (p = 0.01). The 1-, 3- and 5-year actuarial survival rates after RFA were 98.2%, 86.2% and 79.0% in the HCC ≤2 cm group vs. 93.3%, 77.6% and 70.9% in the HCC2 cm group (p = 0.01). Tumor size2 cm (hazard ratio 1.94; 95%CI 1.25-3.02) and alpha-fetoprotein levels at the time of ablation (100-1,000 ng/ml: hazard ratio 2.05; 95%CI 1.10-3.83) were found to be predictors of post-RFA recurrence outside Milan criteria.RFA for single HCC ≤3 cm provides excellent short- to medium-term survival. However, we identified patients at higher risk of recurrence beyond Milan criteria. For these patients, liver transplantation should be considered immediately after the first HCC recurrence following RFA.Radiofrequency ablation and liver transplantation are treatment options for early stages of hepatocellular carcinoma (HCC). After ablation some patients will experience recurrence or metastatic spread of the initial tumor or may develop new tumors within the liver. Despite close follow-up, these recurrences can progress rapidly and exceed transplant criteria, preventing the patient from receiving a transplant. We identified that patients with HCC2 cm and higher serum alpha-fetoprotein are at greater risk of recurrence beyond the transplant criteria. These data suggest that liver transplantation should be considered immediately after the first HCC recurrence for these patients.

The outcome after living donor liver transplantation (LDLT) using grafts with multiple bile ducts (BDs) remains unclear. We analyzed 510 patients who received an adult-to-adult right lobe LDLT between 2000 and 2015 and compared outcome parameters of those receiving grafts with 2 BDs (n = 169) with patients receiving grafts with 1 BD (n = 320). Additionally, patients receiving a graft with 3 BDs (n = 21) were analyzed. Demographic variables and disease severity were similar between the groups. Roux-en-Y reconstruction was significantly more common in the 2 BD group (77% versus 38%; P < 0.001) compared with the 1 BD group. No difference was found in biliary complication rates within 1 year after LDLT (1 BD versus 2 BD groups, 18% versus 21%, respectively; P = 0.46). In the 2 BD group, 82/169 (48.5%) patients were reconstructed with 2 anastomoses. The number of anastomoses did not negatively impact biliary complication rates. Recipients' major complication rate (Clavien ≥ 3b) was similar between both groups (1 BD versus 2 BD groups, 21% versus 24%, respectively; P = 0.36). Furthermore, no difference could be found between the 1 BD, the 2 BD, and the 3 BD groups in the frequency of developing biliary complications within 1 year (18%, 21%, 14%, respectively; P = 0.64), BD strictures (15%, 15%, 5%, respectively; P = 0.42), or BD leaks (10%, 11%, 10%, respectively; P = 0.98). In addition, the 1-year (90% versus 91%), 5-year (82% versus 77%), and 10-year (70% versus 66%) graft survival rates as well as the 1-year (92% versus 93%), 5-year (84% versus 80%), and 10-year (75% versus 76%) patient survival rates were comparable between the 1 BD and the 2 BD groups (P = 0.41 and P = 0.54, respectively). In conclusion, this study demonstrates that selected living donor grafts with 2 BDs can be used safely without negatively impacting biliary complication rates and graft or patient survival rates.

Portal vein thrombosis (PVT) is a severe complication after liver transplantation that can result in increased morbidity and mortality. Few data are available regarding risk factors, classification, and treatment of PVT after living donor liver transplantation (LDLT). Between January 2004 and November 2014, 421 adult-to-adult LDLTs were performed at our institution, and they were included in the analysis. Perioperative characteristics and outcomes from patients with no-PVT (n = 393) were compared with those with de novo PVT (total portal vein thrombosis [t-PVT]; n = 28). Ten patients had early portal vein thrombosis (e-PVT) occurring within 1 month, and 18 patients had late portal vein thrombosis (l-PVT) appearing later than 1 month after LDLT. Analysis of perioperative variables determined that splenectomy was associated with t-PVT (hazard ratio [HR], 3.55; P = 0.01), e-PVT (HR, 4.96; P = 0.04), and l-PVT (HR, 3.84; P = 0.03). In contrast, donor age was only found as a risk factor for l-PVT (HR, 1.05; P = 0.01). Salvage rate for treatment in e-PVT and l-PVT was 100% and 50%, respectively, without having an early event of rethrombosis. Mortality within 30 days did not show a significant difference between groups (no-PVT, 2% versus e-PVT, 10%; P = 0.15). No significant differences were found regarding 1-year (89% versus 92%), 5-year (79% versus 82%), and 10-year (69% versus 79%) graft survival between the t-PVT and no-PVT groups, respectively (P = 0.24). The 1-year (89% versus 96%), 5-year (82% versus 86%), and 10-year (79% versus 83%) patient survival was similar for the patients in the no-PVT and t-PVT groups, respectively (P = 0.70). No cases of graft loss occurred as a direct consequence of PVT. In conclusion, the early diagnosis and management of PVT after LDLT can lead to acceptable early and longterm results without affecting patient and graft survival.

Because of the shortfall between the number of patients listed for liver transplantation (LT) and the available grafts, strategies to expand the donor pool have been developed. Donation after circulatory death (DCD) and living donor (LD) grafts are not universally used because of the concerns of graft failure, biliary complications, and donor risks. In order to overcome the barriers for the implementation of using all 3 types of grafts, we compared outcomes after LT of DCD, LD, and donation after brain death (DBD) grafts. Patients who received a LD, DCD, or DBD liver graft at the University of Toronto were included. Between January 2009 through April 2017, 1054 patients received a LT at our center. Of these, 77 patients received a DCD graft (DCD group); 271 received a LD graft (LD group); and 706 received a DBD graft (DBD group). Overall biliary complications were higher in the LD group (11.8%) compared with the DCD group (5.2%) and the DBD group (4.8%; P < 0.001). The 1‐, 3‐, and 5‐year graft survival rates were similar between the groups with 88.3%, 83.2%, and 69.2% in the DCD group versus 92.6%, 85.4%, and 84.7% in the LD group versus 90.2%, 84.2%, and 79.9% in the DBD group (P = 0.24). Furthermore, the 1‐, 3‐, and 5‐year patient survival was comparable, with 92.2%, 85.4%, and 71.6% in the DCD group versus 95.2%, 88.8%, and 88.8% in the LD group versus 93.1%, 87.5%, and 83% in the DBD group (P = 0.14). Multivariate Cox regression analysis revealed that the type of graft did not impact graft survival. In conclusion, DCD, LD, and DBD grafts have similar longterm graft survival rates. Increasing the use of LD and DCD grafts may improve access to LT without affecting graft survival rates. Liver Transplantation 24 779–789 2018 AASLD.

This multicentric study of 17 high-volume centers presents 12 benchmark values for liver transplantation. Those values, mostly targeting markers of morbidity, were gathered from 2024 "low risk" cases, and may serve as reference to assess outcome of single or any groups of patients.To propose benchmark outcome values in liver transplantation, serving as reference for assessing individual patients or any other patient groups.Best achievable results in liver transplantation, that is, benchmarks, are unknown. Consequently, outcome comparisons within or across centers over time remain speculative.Out of 7492 liver transplantation performed in 17 international centers from 3 continents, we identified 2024 low risk adult cases with a laboratory model for end-stage liver disease score ≤20 points, a balance of risk score ≤9, and receiving a primary graft by donation after brain death. We chose clinically relevant endpoints covering intra- and postoperative course, with a focus on complications graded by severity including the complication comprehensive index (CCI). Respective benchmarks were derived from the median value in each center, and the 75 percentile was considered the benchmark cutoff.Benchmark cases represented 8% to 49% of cases per center. One-year patient-survival was 91.6% with 3.5% retransplantations. Eighty-two percent of patients developed at least 1 complication during 1-year follow-up. Biliary complications occurred in one-fifth of the patients up to 6 months after surgery. Benchmark cutoffs were ≤4 days for ICU stay, ≤18 days for hospital stay, ≤59% for patients with severe complications (≥ Grade III) and ≤42.1 for 1-year CCI. Comparisons with the next higher risk group (model for end stage liver disease 21-30) disclosed an increase in morbidity but within benchmark cutoffs for most, but not all indicators, while in patients receiving a second graft from 1 center (n = 50) outcome values were all outside of benchmark values.Despite excellent 1-year survival, morbidity in benchmark cases remains high with half of patients developing severe complications during 1-year follow-up. Benchmark cutoffs targeting morbidity parameters offer a valid tool to assess higher risk groups.

Patients with hepatocellular carcinoma (HCC) beyond the traditional criteria (advanced HCC) are typically offered palliation, which is associated with a 3-year survival rate lower than 30%. This study aimed to describe the outcomes for a subset of patients with advanced HCC who satisfied the Extended Toronto Criteria (ETC) and were listed for liver transplantation (LT).All patients listed in the Toronto liver transplantation program with HCC beyond both the Milan and University of California, San Francisco criteria were included in this study. Data were extracted from the prospectively collected electronic database. All radiologic images were reviewed by two independent radiologists. The primary end point was patient survival.Between January 1999 and August 2014, 96 patients with advanced HCC were listed for LT, and 62 (65%) of these patients received bridging therapy while on the waiting list. Bridging therapy led to a significant reduction in tumor progression (p = 0.02) and tumor burden (p 0.001). The majority of those listed underwent LT (n = 69, 72%). Both tumor progression on waiting list (hazard ratio [HR] 4.973; range1.599-15.464; p = 0.006) and peak alpha-fetoprotein (AFP) at 400 ng/ml or higher (HR, 4.604; range 1.660-12.768; p = 0.003) were independently associated with waiting list dropout. Post-LT HCC recurrence occurred in 35% of the patients (n = 24). Among those with HCC recurrence, survival was significantly better for those who received curative treatment (p = 0.004). The overall actuarial survival rates from the listing were 76% at 1 year, 56% at 3 years, and 47% at 5 years, and the corresponding rates from LT were 93, 71, and 66%.Liver transplantation provides significantly better survival rates than palliation for patients with selected advanced HCC.

Background: Hepatocellular carcinoma (HCC) remains a major health issue because of its increasing incidence and because of the complexity of its management. In addition to the traditional potentially curative treatments, i.e., liver transplantation and surgical resection, other new and emerging local therapies have been applied with promising results. Summary: Radiotherapy (RT) and interstitial treatments, such as radiofrequency ablation (RFA), microwave ablation (MWA), and irreversible electroporation (IRE), have recently opened new and interesting treatment scenarios for HCC and are associated with promising results in selected patients. Herein, we describe the emerging role of interventional oncology for the treatment of HCC and focus on the different Western and Eastern approaches. Key Messages: Modern RT and modern interstitial therapies, such as RFA, MWA, and IRE, should be considered for inclusion in HCC therapy guidelines.

Objective: To compare the outcome of adult live donor liver transplantation (LDLT) with grafts from older versus younger donors. Introduction: Using older donor grafts for adult LDLT may help expand the donor pool. However, the risks of LDLT with older donors remain controversial, and many centers are reluctant to use live donors aged 45 years or older for adult LDLT. Methods: Outcomes of patients receiving a LDLT graft from donors aged 50 years or older (n = 91) were compared with those receiving a live donor graft from donors younger than 50 years (n = 378). Results: Incidences of biliary (LDLT

The potential for integrating real-time surgical video and state-of-the art animation techniques has not been widely applied to surgical education. This paper describes the use of new technology for creating videos of liver, pancreas and transplant surgery, annotating them with 3D animations, resulting in a freely-accessible online resource: The Toronto Video Atlas of Liver, Pancreas and Transplant Surgery ( http://tvasurg.ca ). The atlas complements the teaching provided to trainees in the operating room, and the techniques described in this study can be readily adapted by other surgical training programmes.

There are conflicting reports on the outcomes after live donor liver transplantation in patients with hepatocellular carcinoma (HCC). We aimed to compare the survival of patients with HCC, with a potential live donor (pLDLT) at listing vs. no potential donor (pDDLT), on an intention-to-treat basis.All patients with HCC listed for liver transplantation between 2000-2015 were included. The pLDLT group was comprised of recipients with a potential live donor identified at listing. Patients without a live donor were included in the pDDLT group. Survival was assessed by the Kaplan-Meier method. Multivariable Cox regression was applied to identify potential predictors of mortality.A total of 219 patients were included in the pLDLT group and 632 patients in the pDDLT group. In the pLDLT group, 57 patients (26%) were beyond the UCSF criteria whereas 119 patients (19%) in the pDDLT group were beyond (p = 0.02). Time on the waiting list was shorter for the pLDLT than the pDDLT group (4.8 [2.9-8.5] months vs. 6.2 [3.0-12.0] months, respectively, p = 0.02). The dropout rate was 32/219 (14.6%) in the pLDLT and 174/632 (27.5%) in the pDDLT group, p 0.001. The 1-, 3- and 5-year intention-to-treat survival rates were 86%, 72% and 68% in the pLDLT vs. 82%, 63% and 57% in the pDDLT group, p = 0.02. Having a potential live donor was a protective factor for death (hazard ratio [HR] 0.67; 95% CI 0.53-0.86). Waiting times of 9-12 months (HR 1.53; 95% CI 1.02-2.31) and ≥12 months (HR 1.69; 95% CI 1.23-2.32) were predictors of death.Having a potential live donor at listing was associated with a significant decrease in the risk of death in patients with HCC in this intention-to-treat analysis. This benefit is related to a lower dropout rate and a shorter waiting period.Liver transplantation (LT) offers the best chance of survival for patients with hepatocellular carcinoma and can be performed using grafts from deceased donors or live donors. In this work, we aimed to assess the differences in survival after live donor LT when compared to deceased donor LT. We studied 219 patients listed for live donor LT and 632 patients listed for deceased donor LT. Patients who had a potential live donor at the time of listing had a higher survival rate. Therefore, being listed for a live donor LT was a protective factor against death.

Objective: To report the role of liver transplantation in the management of refractory carcinoid syndrome. Methods: We describe the clinical course, biochemical, radiographic, and histopathologic features of a patient with severe refractory carcinoid syndrome due to a metastatic well-differentiated enterochromaffin cell neuroendocrine tumor of the jejunum. We also review and summarize the literature on liver transplantation in this setting. Results: An 18-year-old patient presented with a 3-year history of progressive palpitations, flushing, abdominal pain, and diarrhea. Initial imaging studies demonstrated multiple cystic liver lesions; biochemistry confirmed elevated 24-hour urinary 5-hydroxy-indolacetic acid (5-HIAA) levels. She was managed with somatostatin analogues followed by a partial small-bowel resection. Five sessions of liver embolization and escalating somatostatin analogues failed to control her symptoms or normalize urinary 5-HIAA levels. Cross-sectional imaging detected disease only in the liver. Due to progressively worsening symptoms, liver transplantation was offered as a therapeutic option at age 21 years. One year following the procedure, her condition improved clinically and biochemically with minimal disease outside the liver. Conclusion: Liver transplantation represents a potential therapeutic option in selected patients with refractory carcinoid syndrome.

Background The use of venovenous bypass in liver transplantation has declined over time. Few studies have examined the impact of surgical approach in cases performed exclusively without venovenous bypass. We hypothesized that advances in liver transplant anesthesia and perioperative care have minimized the importance of surgical approach in the modern era. Methods Deceased donor liver transplants at the University of Toronto from 2000 to 2015 were reviewed, all performed without venovenous bypass. First, an unadjusted analysis was performed comparing perioperative outcomes and graft/patient survival for 3 different liver transplant techniques (caval interposition, piggyback, side-to-side cavo-cavostomy). Second, a propensity-matched analysis was performed comparing caval interposition to caval-preserving techniques. Results One thousand two hundred thirty-three liver transplants were included in the study. On unadjusted analysis, blood loss, transfusion requirement, postoperative complications, and graft/patient survival were equivalent for the 3 different techniques. To account for possible confounding patient variables, propensity matching was performed. Analysis of the propensity-matched cohorts also demonstrated similar outcomes for caval interposition versus caval-preserving approaches. Conclusions In the modern era at centers with a multidisciplinary team, the importance of specific liver transplant technique is minimized. Full or partial cross-clamping of the inferior vena cava is feasible without the use of venovenous bypass.

The authors assessed the incidence, management, and risk factors for postoperative complications after right lobe (RL) live donor hepatectomy in a high-volume center in North America. All donors undergoing an RL live donor hepatectomy between 2000 and 2017 at our institution were included. The primary outcome was the development of complications (both medical and surgical). Predictors of postoperative complications were determined by logistic regression. A total of 587 patients underwent RL live donor hepatectomy. Among those, 187 postoperative complications were diagnosed in 141 (24%) patients. One patient had >90-day morbidity, and there were no donor deaths. Overall complications were significantly higher in the first era, 2000 to 2008 (81 [57.4%]) versus the second era, 2009 to 2017 (60 [42.6%]) (p = 0.01). On multivariate analysis, the only predictor of postoperative complications was the center volume of RL live donor hepatectomy in the previous 12 months with an odds ratio of 0.97 (95% confidence interval: 0.95–0.99). In conclusion, increasing center volume is associated with lower rates of postoperative complications after RL living liver donation.

Nonalcoholic fatty liver disease (NAFLD) can occur de novo in patients undergoing liver transplantation (LT) for indications other than NAFLD, and it has been increasingly recognized as a complication in the post-LT setting. This study aims to better characterize de novo NAFLD after LT by identifying risk factors for its development, describing incidence and extent of fibrosis, assessing the diagnostic utility of noninvasive serum fibrosis algorithms, and comparing survival to those without NAFLD. This was a retrospective single-center analysis of de novo NAFLD in a post-LT cohort. Those whose primary indication for LT was nonalcoholic steatohepatitis (NASH) were excluded. Risk factors were analyzed by univariate and multivariate analyses. De novo NAFLD and fibrosis were assessed on posttransplant liver biopsies, and noninvasive fibrosis scores were calculated from concomitant blood tests. After applying the exclusion criteria, 430 for-cause post-LT biopsies were evaluated; 33.3% (n = 143) had evidence of de novo steatosis and/or NASH at a median of 3.0 years after transplant. On multivariate analysis, body mass index (BMI; odds ratio [OR], 1.12; P < 0.001), diabetes mellitus (OR, 3.01; P = 0.002), hepatitis C virus (OR, 4.61; P < 0.001), weight gain (OR, 1.03; P = 0.007), and sirolimus use (OR, 3.11; P = 0.02) were predictive of de novo NAFLD after LT. Significant fibrosis (≥F2) was present in almost 40% of the cohort. Noninvasive serum fibrosis scores were not useful diagnostic tests. There was no significant difference in the short-term or longterm survival of patients who developed de novo NAFLD. In conclusion, diabetes, BMI, weight gain after LT, and sirolimus-based immunosuppression, in keeping with insulin resistance, were the only modifiable factors associated with development of de novo NAFLD. A significant proportion of patients with de novo NAFLD had fibrosis and given the limited utility of noninvasive serum fibrosis algorithms, alternative noninvasive tools are required to screen for fibrosis in this population. There was no significant difference in the short-term or longterm survival of patients who developed de novo NAFLD.

Background Liver transplant (LT) for nonalcoholic steatohepatitis (NASH) related hepatocellular carcinoma (HCC) is not well characterized in the literature. The aim of the study was to examine characteristics and outcomes of patients who had LT for NASH-HCC (NASH) versus HCC from other liver diseases (non-NASH). Methods Using a 2-center retrospective design, all patients from 2004 to 2014 that received LT for HCC were analyzed. Subgroup analysis stratified patients according to Milan criteria. Results Nine hundred twenty-nine patients were transplanted for HCC. Sixty (6.5%) of 929 had HCC in the context of NASH. There were no significant differences between groups for pretransplant or explant tumor characteristics. The actuarial 1-, 3- and 5-year overall survival was 98%, 96%, and 80% in NASH versus 95%, 84%, and 78% in non-NASH (P = 0.1). No differences in tumor recurrence were observed in patients within and beyond Milan in the NASH group. Multivariate Cox regression demonstrated NASH status to be a protective factor for recurrence among patients with tumors beyond Milan (hazard ratio, 0.21; 95% confidence interval, 0.05-0.86; P = 0.029). Conclusion After LT, outcomes are similar between NASH and non-NASH etiologies for HCC. The hypothesis that patients with more advanced HCC tumors in the context of NASH may have more favorable outcomes after LT has been generated, but requires further study.

Because of a persistent discrepancy between the demand for liver transplantation (LT) and the supply of deceased donor organs, there is an interest in increasing living donation rates at centers trained in this method of transplantation. We examined a large socioeconomically heterogeneous cohort of patients listed for LT to identify recipient factors associated with living donation. We retrospectively reviewed 491 consecutive patients who were listed for LT at our center over a 24-month period. Demographic, medical, and socioeconomic data were extracted from electronic records and compared between those who had a potential living donor (LD) volunteer for assessment and those who did not; 245 patients (50%) had at least 1 potential LD volunteer for assessment. Multivariate logistic regression analysis identified that patients with a LD were more likely to have Child-Pugh C disease (odds ratio [OR], 2.44; P = 0.02), and less likely to be older (OR, 0.96; P = 0.002), single (OR, 0.34; P = 0.006), divorced (OR, 0.53; P = 0.03), immigrants (OR, 0.38; P = 0.049), or from the lowest income quintile (OR, 0.44; P = 0.02). In conclusion, this analysis has identified several factors associated with access to living donation. More research is warranted to define and overcome barriers to living donor liver transplantation through targeted interventions in underrepresented populations. Liver Transpl 21:897-903, 2015. © 2015 AASLD.

Data regarding transplantation outcomes in ventilated intensive care unit (ICU)–dependent patients with end-stage liver disease (ESLD) are conflicting. This single-center cohort study investigated the outcomes of patients with ESLD who were intubated with mechanical support before liver transplantation (LT). The ICU plus intubation group consisted of 42 patients with decompensated cirrhosis and mechanical ventilation before transplantation. LT was considered for intubated ICU patients if the fraction of inspired oxygen was ≤40% with a positive end-expiratory pressure ≤ 10, low pressor requirements, and the absence of an active infection. Intubated ICU patients were compared to 80 patients requiring ICU admission before transplantation without intubation and to 126 matched non–ICU-bound patients. Patients requiring ICU care with intubation and ICU care alone had more severe postoperative complications than non–ICU-bound patients. Intubation before transplantation was associated with more postoperative pneumonias (15% in intubated ICU transplant candidates, 5% in ICU-bound but not intubated patients, and 3% in control group patients; P = 0.02). Parameters of reperfusion injury and renal function on postoperative day (POD) 2 and POD 7 were similar in all groups. Bilirubin levels were higher in the ICU plus intubation group at POD 2 and POD 7 after transplantation but were normalized in all groups within 3 months. The ICU plus intubation group versus the ICU-only group and the non-ICU group had decreased 1-, 3-, and 5-year graft survival (81% versus 84% versus 92%, 76% versus 78% versus 87%, and 71% versus 77% versus 84%, respectively; P = 0.19), but statistical significance was not reached. A Glasgow coma scale score of 7 before transplantation was associated with high postoperative mortality in ICU-bound patients requiring intubation (38% versus 23%; P = 0.01). In conclusion, ICU admission and mechanical ventilation should not be considered contraindications for LT. With careful patient selection, acceptable long-term outcomes can be achieved despite increased postoperative complications. Liver Transpl 21:761–767, 2015. © 2015 AASLD.

Long-term biliary complications after living donor liver transplantation (LDLT) are not well described in the literature. This study was undertaken to determine the long-term impact of biliary complications after adult right-lobe LDLT.This retrospective review analyzed an 11-yr experience of 344 consecutive right-lobe LDLTs with at least two yr of follow-up.Biliary leaks occurred in 50 patients (14.5%), and strictures occurred in 67 patients (19.5%). Cumulative biliary complication rates at 1, 2, 5, and 10 yr were 29%, 32%, 36%, and 37%, respectively. Most early biliary leaks were treated with surgical drainage (N = 29, 62%). Most biliary strictures were treated first with endoscopic retrograde cholangiography (42%). There was no association between biliary strictures and the number of ducts (hazard ratio [HR] 1.017 [0.65-1.592], p = 0.94), but freedom from biliary stricture was associated with a more recent era (2006-2010) (HR 0.457 [0.247-0.845], p = 0.01). Long-term graft survival did not differ between those who had or did not have biliary complications (66% vs. 67% at 10 yr).Biliary strictures are common after LDLT but may decline with a center's experience. With careful follow-up, they can be successfully treated, with excellent long-term graft survival rates.

Liver transplantation (LT) with donation after circulatory death (DCD) donors has been associated with a high rate of ischemic-type biliary strictures (ITBSs) and inferior graft survival. To investigate the impact of an intraoperative tissue plasminogen activator (tPA) on outcomes following DCD LT, we conducted a retrospective analysis of DCD LT at the Toronto General Hospital (TGH) and the Ochsner Medical Center (OMC). Between 2009 and 2013, 85 DCD LTs were performed with an intraoperative tPA injection (n=30 at TGH, n=55 at OMC), and they were compared with 33 DCD LTs without a tPA. Donor and recipient characteristics were similar in the 2 groups. There was no significant difference in the intraoperative packed red blood cell transfusion requirement (3.2 +/- 3.4 versus 3.1 +/- 2.3 U, P=0.74). Overall, biliary strictures occurred less commonly in the tPA-treated group (16.5% versus 33.3%, P=0.07) with a much lower rate of diffuse intrahepatic strictures (3.5% versus 21.2%, P=0.005). After 1 and 3 years, the tPA group versus the non-tPA group had superior patient survival (97.6% versus 87.0% and 92.7% versus 79.7%, P=0.016) and graft survival (96.4% versus 69.7% and 90.2% versus 63.6%, P

Liver resection (LR) and radiofrequency ablation (RFA) are curative-intent therapies for early stages of hepatocellular carcinoma (HCC). If HCC recurs, salvage liver transplant (SLT) may constitute a treatment option. We aimed to compare the outcomes of patients transplanted for recurrent HCC after curative-intent therapies with those transplanted as initial therapy. We conducted a matched-control (1:1) cohort study comparing patients with HCC treated with primary liver transplant (PLT) with SLT after HCC recurrence. Matching was performed according to the size and number of viable tumors at explant pathology following liver transplant. Between November 1999 and December 2014, 687 patients with HCC were listed for transplant at our institution. A total of 559 patients were transplanted; 509 patients were treated with PLT and 50 patients were treated with SLT for HCC recurrence after primary treatment with LR (n = 25) or RFA (n = 25). The median length of follow-up from transplant was 64 months (0.5–195), and the median time from curative-intent treatment of HCC with RFA or LR to recurrence was 9.5 months (1–36) and 14.5 months (3–143), respectively (p = 0.04). The matched cohort was composed of 48 SLT patients (23 LR and 25 RFA) and 48 PLT patients. The 5-year risk of recurrence after LT was 22% in the PLT group versus 32% in the SLT group (p = 0.53), while the 5-year actuarial patient survival after PLT was 69% versus 70% in the SLT group (p = 1). Liver transplant is an effective treatment for patients with HCC recurrence following RFA or LR. Outcomes are similar in both groups.

ImportanceSeveral factors are associated with increased hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT), but no reliable risk score has been established to determine the individual risk for HCC recurrence.ObjectiveWe aimed to develop and validate a Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score for patients with HCC meeting Milan criteria by imaging.Design, setting, and participantsPredictors of recurrence were tested in a development cohort of 721 patients who underwent LT between 2002 and 2012 at 3 academic transplant centers (University of California-San Francisco; Mayo Clinic, Rochester; and Mayo Clinic, Jacksonville) to create the RETREAT score. This was subsequently validated in a cohort of 341 patients also meeting Milan criteria by imaging who underwent LT at the University of Toronto transplant center using the C concordance statistic and net reclassification index.Main outcomes and measuresCharacteristics associated with post-LT HCC recurrence.ResultsA total of 1061 patients participated in the study; 77.8% (825) were men, and the median (IQR) age was 58.2 (53.3-63.9) years in the development cohort and 56.4 (51.7-61.0) years in the validation cohort (P

Whether and when recovery beyond the need for transplant may occur in patients listed for decompensation remains unclear. This study aimed to investigate the characteristics of patients delisted following recompensation. Seventy-seven patients who were listed between 2005 and 2015 for decompensation, but later delisted following recompensation were included. Alcohol-related liver disease (ALD) was the underlying etiology in the majority (n = 47, 61%). Listing characteristics of these patients were compared with those of decompensated ALD patients who either underwent deceased donor liver transplantation or died on the waiting list. The model for end-stage liver disease (MELD) score

BACKGROUND AND OBJECTIVES Neoadjuvant chemoradiation and liver transplantation may be offered for unresectable perihilar cholangiocarcinoma (pCCA). This study aimed to determine the dropout rate and survival of patients who entered a national tri-modality protocol. METHOD Patients enrolled Jan 2009-Aug 2015 were included. Enrolment criteria: ≤65 years, brush biopsy-proven unresectable pCCA

Background In parallel with the obesity epidemic, liver transplantation for nonalcoholic steatohepatitis (NASH) is increasing dramatically in North America. Although survival outcomes are similar to other etiologies, liver transplantation in the NASH population has been associated with significantly increased resource utilization. We sought to compare outcomes between live donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) at a high volume North American transplant center, with a particular focus on resource utilization. Methods The study population consists of primary liver transplants performed for NASH at Toronto General Hospital from 2000 to 2014. Recipient characteristics, perioperative outcomes, graft and patient survivals, and resource utilization were compared for LDLT versus DDLT. Results A total of 176 patients were included in the study (48 LDLT vs 128 DDLT). LDLT recipients had a lower model for end-stage liver disease score and were less frequently hospitalized prior to transplant. Estimated blood loss and early markers of graft injury were lower for LDLT. LDLT recipients had a significantly shorter hospitalization (intensive care unit, postoperative, and total hospitalization). Conclusions LDLT for NASH facilitates transplantation of patients at a less severe stage of disease, which appears to promote a faster postoperative recovery with less resource utilization.

Dense tissue infiltrates of IgG4(+) plasma cells50/high-powered field (HPF) are purportedly highly specific for IgG4-related disease. However, the frequency and significance of liver-infiltrating IgG4(+) plasma cells in primary sclerosing cholangitis (PSC) applying these cut-offs has not been determined. We sought to determine the incidence of intrahepatic IgG4-positive staining in PSC patients undergoing transplantation, correlating findings with clinical parameters. Immunohistochemical staining was performed on liver explants obtained between 1991 and 2009. Of 122 explants obtained, hilar IgG4(+) staining was found to be mild (10-29 IgG4(+) cells/HPF) in 23.0%, moderate (30-50/HPF) in 9.0% and marked (50/HPF) in 15.6%. Marked hilar lymphoplasmacytic infiltration was significantly associated with marked hilar IgG4(+) staining (P 0.001). No patient had marked peripheral IgG4(+) staining, although mild and moderate staining was observed in 24.5% and 3.3% respectively. Marked hilar IgG4(+) staining was significantly associated with the presence of dominant biliary strictures (P = 0.01) and need for biliary stenting (P = 0.001). There did not, however, exist any significant differences in the age at PSC diagnosis, presence of inflammatory bowel disease or extrahepatic autoimmune disease, frequency of cholangiocarcinoma, interval between diagnosis and transplantation, or post-transplant PSC recurrence or survival. Of 51 control liver sections (PBC = 18; HCV = 19; HBV = 8; AIH = 6), none had marked or moderate hilar IgG4(+) staining, whereas mild staining was seen in only 10% (P 0.001). Marked (50/HPF) hilar IgG4(+) lymphoplasmacytic infiltration is frequently observed in PSC and associated with the presence of dominant biliary strictures. However, unlike serum IgG4(+) , this does not seemingly associate with clinical disease course.

Background The role of liver resection in patients with multifocal hepatocellular carcinoma (HCC) with well preserved liver function is controversial. This study was conducted to evaluate the outcomes of such patients. Methods This was a retrospective analysis of patients who underwent liver resection for multifocal HCC between 1992 and 2011. Postoperative outcomes, survival and predictors of outcomes were analysed. Results Of 46 patients who underwent hepatic resection for multifocal HCC, 38 had Barcelona Clinic Liver Cancer stage B disease. Major hepatectomy was performed in 27 patients, and major complications occurred in nine (20 per cent). The 90-day postoperative mortality rate was 7 per cent. Overall 1-, 2-, 3- and 5-year survival rates were 78, 64, 59 and 53 per cent respectively (median 70 months), whereas corresponding recurrence-free survival rates were 53, 32, 30 and 27 per cent (median 14 months). Recurrence developed in 28 (61 per cent) of the 46 patients, affecting the liver only in 22. Three-quarters of patients with recurrence underwent further therapy. Major hepatectomy (hazard ratio (HR) 0.37, 95 per cent confidence interval 0.14 to 0·95; P = 0·038), microvascular (HR 3·44, 1·35 to 8·74; P = 0·009) and macrovascular (HR 2·68, 1·11 to 6·43; P = 0·028) invasion, and cirrhosis (HR 3·15, 1·12 to 8·86; P = 0·029) were associated with overall survival. Microvascular invasion (HR 2·81, 1·06 to 7·40; P = 0·037), cirrhosis (HR 3·12, 1·41 to 6·88; P < 0·001) and bilobar disease (HR 2·93, 1·09 to 7·88; P = 0·033) were associated with recurrence-free survival. Conclusion In selected patients with multifocal HCC and well preserved liver function, long-term survival is possible after liver resection and subsequent aggressive treatment of recurrence.

Experimental studies suggest that the regenerating liver provides a "fertile field" for the growth of hepatocellular carcinoma (HCC). However, clinical studies report conflicting results comparing living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) for HCC. Thus, disease-free survival (DFS) and overall survival (OS) were compared after LDLT and DDLT for HCC in a systematic review and meta-analysis. Twelve studies satisfied eligibility criteria for DFS, including 633 LDLT and 1232 DDLT. Twelve studies satisfied eligibility criteria for OS, including 637 LDLT and 1050 DDLT. Altogether, there were 16 unique studies; 1, 2, and 13 of these were rated as high, medium, and low quality, respectively. Studies were heterogeneous, non-randomized, and mostly retrospective. The combined hazard ratio was 1.59 (95% confidence interval [CI]: 1.02-2.49; I(2) = 50.07%) for DFS after LDLT vs. DDLT for HCC, and 0.97 (95% CI: 0.73-1.27; I(2) = 5.68%) for OS. This analysis provides evidence of lower DFS after LDLT compared with DDLT for HCC. Improved study design and reporting is required in future research to ascribe the observed difference in DFS to study bias or biological risk specifically associated with LDLT.

Background & Aims There is limited information on the use of stereotactic body radiotherapy (SBRT) as a bridge to liver transplantation for hepatocellular carcinoma and no study comparing its efficacy to transarterial chemoembolization (TACE) and radiofrequency ablation (RFA). We aimed to ascertain the safety and efficacy of SBRT on an intention-to-treat basis compared with TACE and RFA as a bridge to liver transplantation in a large cohort of patients with hepatocellular carcinoma. Methods Outcomes between groups were compared from the time of listing and from the time of transplant. Between July 2004 and December 2014, 379 patients were treated with either SBRT (n=36, SBRT group), TACE (n=99, TACE group) or RFA (n=244, RFA group). Results The drop-out rate was similar between groups (16.7% SBRT group vs. 20.2% TACE group and 16.8% RFA group, p =0.7); 30 patients were transplanted in the SBRT group, 79 in the TACE group and 203 in the RFA group. Postoperative complications were similar between groups. Patients in the RFA group had more tumor necrosis in the explant. The 1-, 3- and 5-year actuarial patient survival from the time of listing was 83%, 61% and 61% in the SBRT group vs. 86%, 61% and 56% in the TACE group, and 86%, 72% and 61% in the RFA group, p =0.4. The 1-, 3- and 5-year survival from the time of transplant was 83%, 75% and 75% in the SBRT group vs. 96%, 75% and 69% in the TACE group, and 95%, 81% and 73% in the RFA group, p =0.7. Conclusions In conclusion, SBRT can be safely utilized as a bridge to LT in patients with HCC, as an alternative to conventional bridging therapies. Lay summary Patients with liver cancer included in the waiting list for liver transplantation are at risk of tumor progression and death. Stereotactic body radiotherapy may be a good alternative to conventional therapies to reduce this risk.

The increased prevalence of obesity worldwide threatens the pool of living liver donors. Although the negative effects of graft steatosis on liver donation and transplantation are well known, the impact of obesity in the absence of hepatic steatosis on outcome of living donor liver transplantation (LDLT) is unknown. Consequently, we compared the outcome of LDLT using donors with BMI30 versus donors with BMI ≥30. Between April 2000 and May 2014, 105 patients received a right-lobe liver graft from donors with BMI ≥30, whereas 364 recipients were transplanted with grafts from donors with BMI30. Liver steatosis10% was excluded in all donors with BMI30 by imaging and liver biopsies. None of the donors had any other comorbidity. Donors with BMI30 versus ≥30 had similar postoperative complication rates (Dindo-Clavien ≥3b: 2% vs. 3%; p = 0.71) and lengths of hospital stay (6 vs. 6 days; p = 0.13). Recipient graft function, assessed by posttransplant peak serum bilirubin and international normalized ratio was identical. Furthermore, no difference was observed in recipient complication rates (Dindo-Clavien ≥3b: 25% vs. 20%; p = 0.3) or lengths of hospital stay between groups. We concluded that donors with BMI ≥30, in the absence of graft steatosis, are not contraindicated for LDLT.

The European trial investigating normothermic ex vivo liver perfusion (NEVLP) as a preservation technique for liver transplantation (LT) uses gelofusine, a non-US Food and Drug Administration-approved, bovine-derived, gelatin-based perfusion solution. We report a safety and feasibility clinical NEVLP trial with human albumin-based Steen solution. Transplant outcomes of 10 human liver grafts that were perfused on the Metra device at 37 °C with Steen solution, plus 3 units of erythrocytes were compared with a matched historical control group of 30 grafts using cold storage (CS) as the preservation technique. Ten liver grafts were perfused for 480 minutes (340-580 minutes). All livers cleared lactate (final lactate 1.46 mmol/L; 0.56-1.74 mmol/L) and produced bile (61 mL; 14-146 mL) during perfusion. No technical problems occurred during perfusion, and all NEVLP-preserved grafts functioned well after LT. NEVLP versus CS had lower aspartate aminotransferase and alanine aminotransferase values on postoperative days 1-3 without reaching significance. No difference in postoperative graft function between NEVLP and CS grafts was detected as measured by day 7 international normalized ratio (1.1 [1-1.56] versus 1.1 [1-1.3]; P = 0.5) and bilirubin (1.5; 1-7.7 mg/dL versus 2.78; 0.4-15 mg/dL; P = 0.5). No difference was found in the duration of intensive care unit stay (median, 1 versus 2 days; range, 0-8 versus 0-23 days; P = 0.5) and posttransplant hospital stay (median, 11 versus 13 days; range, 8-17 versus 7-89 days; P = 0.23). Major complications (Dindo-Clavien ≥ 3b) occurred in 1 patient in the NEVLP group (10%) compared with 7 (23%) patients in the CS group (P = 0.5). No graft loss or patient death was observed in either group. Liver preservation with normothermic ex vivo perfusion with the Metra device using Steen solution is safe and results in comparable outcomes to CS after LT. Using US Food and Drug Administration-approved Steen solution will avoid a potential regulatory barrier in North America. Liver Transplantation 22 1501-1508 2016 AASLD.

Liver transplantation (LT) is the treatment of choice for end-stage autoimmune liver diseases. However, the underlying disease may recur in the graft in some 20% of cases. The aim of this study is to determine whether LT using living donor grafts from first-degree relatives results in higher rates of recurrence than grafts from more distant/unrelated donors. Two hundred sixty-three patients, who underwent a first LT in the Toronto liver transplant program between January 2000 and March 2015 for autoimmune liver diseases, and had at least 6 months of post-LT follow-up, were included in this study. Of these, 72 (27%) received a graft from a first-degree living-related donor, 56 (21%) from a distant/unrelated living donor, and 135 (51%) from a deceased donor for primary sclerosing cholangitis (PSC) (n = 138, 52%), primary biliary cholangitis (PBC) (n = 69, 26%), autoimmune hepatitis (AIH) (n = 44, 17%), and overlap syndromes (n = 12, 5%). Recurrence occurred in 52 (20%) patients. Recurrence rates for each autoimmune liver disease were not significantly different after first-degree living-related, living-unrelated, or deceased-donor LT. Similarly, time to recurrence, recurrence-related graft failure, graft survival, and patient survival were not significantly different between groups. In conclusion, first-degree living-related donor LT for PSC, PBC, or AIH is not associated with an increased risk of disease recurrence.

The selection of liver transplant candidates with hepatocellular carcinoma (HCC) relies mostly on tumor size and number. Instead of relying on these factors, we used poor tumor differentiation and cancer-related symptoms to exclude patients likely to have advanced HCC with aggressive biology. We initially reported similar 5-year survival for patients whose tumors exceeded (M+ group) and were within (M group) the Milan criteria. Herein, we validate our original data with a new prospective cohort and report the long-term follow-up (10-years) using an intention-to-treat analysis. The previously published study (cohort 1) included 362 listed (294 transplanted) patients from January 1996 to August 2008. The validation cohort (cohort 2) includes 243 listed (105 M+ group, 76 beyond University of California San Francisco criteria; 210 transplanted) patients from September 2008 to December 2012. Median follow-up from listing was 59.7 (26.8-103) months. For the validation cohort 2, the actuarial survival from transplant for the M+ group was similar to that of the M group at 1 year, 3 years, and 5 years: 94%, 76%, and 69% versus 95%, 82%, and 78% (P = 0.3). For the combined cohorts 1 and 2, there were no significant differences in the 10-year actuarial survival from transplant between groups. On an intention-to-treat basis, the dropout rate was higher in the M+ group and the 5-year and 10-year survival rates from listing were decreased in the M+ group. An alpha-fetoprotein level >500 ng/mL predicted poorer outcomes for both the M and M+ groups. Conclusion Tumor differentiation and cancer-related symptoms of HCC can be used to select patients with advanced HCC who are appropriate candidates for liver transplantation; alpha-fetoprotein level limitations should be incorporated in the listing criteria for patients within or beyond the Milan criteria. (Hepatology 2016;64:2077-2088).

Living liver donation is a successful treatment for patients with end-stage liver disease. Most adults are provided with a right lobe graft to ensure a generous recipient liver volume. Some centers are re-exploring the use of smaller left lobe grafts to potentially reduce the donor risk. However, the evidence showing that the donor risk is lower with left lobe donation is inconsistent, and most previous studies have been limited by potential learning curve effects, small sample sizes, or poorly matched comparison groups. To address these deficiencies, we conducted a case-control study. Forty-five consecutive patients who underwent left hepatectomy (LH; n = 4) or left lateral segmentectomy (LLS; n = 41) were compared with matched controls who underwent right hepatectomy (RH) or extended right hepatectomy (ERH). The overall complication rates of the 3 groups were similar (31%-37%). There were no grade 4 or 5 complications. There were more grade 3 complications for the RH patients (13.3%) and the ERH patients (15.6%) versus the LH/LLS patients (2.2%). The extent of the liver resection significantly correlated with the peak international normalized ratio (INR), the days to INR normalization, and the peak bilirubin level. A univariate analysis demonstrated that hepatectomy, the spared volume percentage, and the peak bilirubin level were strongly associated with grade 3 complications. A higher peak bilirubin level, which correlated with a lower residual liver volume, was associated with grade 3 complications in a multivariate analysis (P = 0.005). RH and grade 3 complications were associated with an increased length of stay (>7 days) in a multivariate analysis. In conclusion, this analysis demonstrates a significant correlation between the residual liver volume and liver dysfunction, serious adverse postoperative events, and longer hospital stays. Donor safety should be the first priority of all living liver donor programs. We propose that the surgical procedure removing the smallest amount of the liver required to provide adequate recipient graft function should become the standard of care for living liver donation.

Biliary strictures after live donor liver transplantation (LDLT) are frequent and difficult to manage. The outcomes of surgical correction of biliary anastomotic complications remain unclear. Clinical outcomes of patients requiring surgical revision of their biliary anastomosis following LDLT were analyzed. Of 296 consecutive right lobe LDLTs, approximately 21% of patients developed biliary strictures. Of these patients, twelve required surgical revision of a biliary anastomotic stricture. For patients who had operative repair, the average time from transplantation to stricture diagnosis was 7.6 months. Mean time to surgical correction was 8.2 months from the time of stricture diagnosis. Eight of 12 (67%) patients no longer require any intervention with a mean follow-up of 43.7 months. Two of 12 patients require intermittent medical treatment for presumed cholangitis, but have not required biliary interventions. Two patients have required chronic PTC catheter drainage. The 30-day postoperative morbidity was 58%, with four serious (Grade 3) complications occurring in three patients. Early stricture repair (

2011 AASLD.Received February 16, 2011; accepted April 27, 2011.By asking whether we should perform deceased donorliver transplantation (DDLT) after living donor livertransplantation (LDLT) has failed, we appear to bequestioning the generally accepted current practice ofretransplantation for transplant failure. However, wewill also consider in this analysis that LDLT may havebeen performed for patients whose tumors werebeyond the local criteria for listing or increased prior-ity on the deceased donor (DD) wait list (ie, thepatients were not eligible for DDLT originally). Toarrive at a recommendation, we will analyze the out-comes and ethical implications of retransplantationby considering the following 4 questions:1. Should we perform DDLT after the failure ofDDLT?2. Should we perform DDLT after the failure ofLDLT in a patient without hepatocellular carci-noma (HCC)?3. Should we perform DDLT after the failure ofLDLT in a patient with HCC who fulfills the localcriteria for listing and increased priority on thewait list?4. Should we perform DDLT after the failure ofLDLT in a patient with HCC who does not fulfillthe local criteria for listing or increased priorityon the wait list (ie, the patient failed to meet thecriteria for DDLT originally)?With questions 1 to 3, we will consider the ethicalfoundation for the current practice of retransplanta-tion for graft failure, and this discussion will serve asthe basis for question 4, which is more controversial.

Liberal acceptance criteria are used when offering liver transplantation (LTx) for treatment of hepatocellular carcinoma (HCC) at our center. This provides a unique opportunity to assess outcomes in a large North American series of patients with advanced tumors.We hypothesized that acceptable survival rates can be achieved with LTx for any size or number of HCC provided that (a) imaging studies ruled out vascular invasion; (b) the HCC was confined to the liver; and (c) the HCC was not poorly differentiated on biopsy.Survival, based on pretransplant imaging staging, was compared between 189 Milan Criteria (M) and 105 beyond Milan Criteria (M+) HCC patients who received an LTx between 1996 and 2008.Imaging understaged 30% of the M group and over staged 23% of the M+ group. There was no difference in the 5-year overall survival in the M (72%) and M+ (70%) groups or 5-year disease-free survival in the M (70%) and M+ (66%) groups. The introduction of a protocol for a biopsy to exclude patients with poorly differentiated tumors and use of aggressive bridging therapy improved overall survival in the M+ group (P = 0.034). Serum alpha-fetoprotein more than 400 at LTx was associated with poorer disease-free survival (hazard ratio: 2.3; P = 0.031).Cross-sectional imaging did not reliably stage patients with HCC for LTx. A protocol using a biopsy to exclude poorly differentiated tumors and aggressive bridging therapy achieved excellent survival rates with LTx for otherwise incurable advanced HCC, irrespective of tumor size and number.

Using our prospectively collected database all adult hepatitis C virus (HCV)-positive patients receiving an adult-to-adult LDLT between October 2000 and May 2014 were identified. Outcome of LDLT with grafts from younger (

Donor safety is the paramount concern of living donor liver transplantation (LDLT). Although LDLT is employed worldwide, there is little data on rates and causes of 'no go' hepatectomies-patients brought to the operating room for possible donor hepatectomy whose procedure was aborted. We performed a single-center, retrospective review of all patients brought to the operating room for donor hepatectomy between October 2000 and November 2008. Of 257 right lobe donors, the donor operation was aborted in 12 cases (4.7%). The main reasons for stopping the operation were aberrant ductal or vascular anatomy (seven cases), unsuitable liver quality (three cases) or unexpected intraoperative events (two cases). Over the median period of follow-up of 23 months, there were no long-term complications of patients with aborted donor procedures. This report focuses exclusively on an important issue: the frequency and causes of no go decisions at a single large volume North American LDLT center. The rate of no go donor hepatectomies should be as low as possible without compromising donor safety--however, even with rigorous preoperative evaluation the rate of donor abortions will be significant. The default surgical position should always be to abort the donor operation if there is an unexpected finding that places the donor at increased risk.

In 2002, the New York State Committee on Quality Improvement in Living Liver Donation prohibited live liver donation for potential recipients with Model for End-stage Liver Disease (MELD) scores greater than 25. Despite the paucity of evidence to support this recommendation, many centers in North America remain reluctant to offer living donor (LD) to patients with moderate to high MELD scores.We analyzed 271 consecutive adult-to-adult right lobe LD liver transplants performed at our institution between 2002 and 2008 to study the relationship, between recipient MELD scores and the outcome of LD liver transplantation. The recipients were categorized according to their MELD score into a low (Low:25)and high (Hi:or=25) MELD group. We compared short-term donor morbidity, graft loss within 30 days, length of hospital stay, biochemical markers of hepatocyte injury and graft function, and 90 day posttransplant complications including infection, rejection, bleeding, and renal failure. Long-term posttransplant outcome was measured by graft and patient survival after 1-, 3-, and 5-years.Donor and recipient characteristics were similar between groups. Donor outcomes were similar in both groups. Peak recipient aspartat aminotransferase, alanine aminotransferase, and length of hospital stay were similar between both groups. The proportional decrease in postoperative INR and creatinine within the first week was greater in the high versus low MELD score group. High MELD score recipients had more frequent postoperative pneumonia (Low: 2.2% vs. Hi: 14%, P = 0.003), while no differences were observed in rates of biliary complications, rejection, renal failure, or overall infections. Recipients with a MELD25 versusor=25 had a similar 1-year (Low: 92% vs. Hi: 83%), 3-year (Low: 86% vs. Hi: 80%), and 5-year (Low: 78% vs. Hi: 80%) graft survival after LD liver transplantation (P = 0.51).LD liver transplantation can provide excellent graft function and survival rates in high MELD score recipients. Thus, when deceased donor organs are scare, a high MELD score alone should not be an absolute contraindication to living liver donation.

Many centers require a minimal graft to body weight ratio (GBWR) ≥ 0.8 as an arbitrary threshold to proceed with right-lobe living donor liver transplantation (RL-LDLT), and there is often hesitancy about transplanting lower volume living donor (LD) liver grafts into sicker patients. The data supporting this dogma, based on the early experience with RL-LDLT at Asian centers, are weak. To determine the effect of LD liver volume in the modern era, we investigated the impact of GBWR on the outcome of RL-LDLT with a GBWR as low as 0.6 at the University of Toronto. Between April 2000 and September 2008, 271 adult-to-adult RL-LDLT procedures and 614 deceased donor liver transplants were performed. Twenty-two living donor liver transplantation (LDLT) cases with a GBWR of 0.59 to 0.79 (group A) were compared with 249 LDLT cases with a GBWR ≥ 0.8 (group B) and with 66 full-graft deceased donor liver transplants (group C), who were matched 3:1 according to donor and recipient age, Model for End-Stage Liver Disease score, and presence of hepatitis C and hepatocellular carcinoma with the low-GBWR group. Portal vein shunts were not used. Markers of reperfusion injury [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], graft function (international normalized ratio and bilirubin), complications graded by the Clavien score, and graft and patient survival were compared. As expected, LD recipients had a significantly shorter cold ischemia time (94 ± 43 minutes for A, 96 ± 57 minutes for B, and 453 ± 152 minutes for C, P = 0.0001). However, the peak AST, peak ALT, absolute decrease in the international normalized ratio, day 7 bilirubin level, postoperative creatinine clearance, complication rate graded by the Clavien score, and median hospital stay were similar in all groups. The rate of biliary complications was higher with LD grafts than deceased donor grafts (19% for A versus 10% for B and 0% for C, P = 0.2). Patient survival was similar in all groups at 1, 3, and 5 years (91% for A versus 89% for B and 93% for C at 1 year, 87% for A versus 81% for B and 89% for C at 3 years, and 83% for A versus 81% for B and 87% for C at 5 years, P = 0.63). A Cox proportional regression analysis revealed only hepatitis C virus as a risk factor for poorer graft survival and not GBWR as a continuous or categorical variable. In conclusion, we found no evidence of inferior outcomes with smaller size grafts versus larger size LD grafts or full-size deceased donor grafts. Further studies are warranted to examine the factors affecting the function of smaller grafts for living liver donation and thereby define the safe lower limits for transplantation. Liver Transpl 15:1776–1782, 2009. © 2009 AASLD.

We studied the role of donor and recipient age in transplantation/ischemia-reperfusion injury (TIRI) and short- and long-term graft and patient survival. Eight hundred twenty-two patients underwent deceased donor liver transplantation, with 197 donors being ≥60 years old. We evaluated markers of reperfusion injury, graft function, and clinical outcomes as well as short- and long-term graft and patient survival. Increased donor age was associated with more severe TIRI and decreased 3- and 5-year graft survival (73% versus 85% and 72% versus 81%, P < 0.001) and patient survival (77% versus 88% and 77% versus 82%, P < 0.003). Hepatitis C virus (HCV) infection and recipient age were the only independent risk factors for graft and patient survival in patients receiving an older graft. In the HCV(+) cohort (297 patients), patients ≥ 50 years old who were transplanted with an older graft versus a younger graft had significantly decreased 3- and 5-year graft survival (68% versus 83% and 64% versus 83%, P < 0.009). In contrast, HCV(+) patients < 50 years old had similar 3- and 5-year graft survival if transplanted with either a young graft or an old graft (81% versus 82% and 81% versus 82%, P = 0.9). In conclusion, recipient age and HCV status affect the graft and patient survival of older livers. Combining older grafts with older recipients should be avoided, particularly in HCV(+) patients, whereas the effects of donor age can be minimized in younger recipients. Liver Transpl 15:1288–1295, 2009. © 2009 AASLD.

Hepatitis C recurs universally after liver transplantation (LT). Whether its progression differs after live donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) is still debated. We retrospectively analyzed 201 consecutive LTs performed at our institution for hepatitis C–related end-stage liver disease between April 2000 and December 2005 (46 LDLTs and 155 DDLTs). Patients were followed with protocol biopsies for medians of 29 (LDLT) and 39 months (DDLT; P = 0.7). Although overall graft and patient survival did not differ, the mean fibrosis stage (Metavir) was significantly higher at 12 to 48 months post-LT (all P 45 years carried a relative risk of 8.17 (confidence interval = 2.6–25.5, P = 0.001) for reaching fibrosis stage 3 or 4 at 2 years post-LT. In conclusion, donor age, rather than the transplant approach, determines the progression of recurrent hepatitis C after LT. LDLT, allowing for the selection of younger donors, may particularly benefit hepatitis C patients. Liver Transpl 14:1778–1786, 2008. © 2008 AASLD.

Criteria for the selection of candidates for liver transplantation in the presence of hepatocellular carcinoma (HCC) should accurately predict posttransplant recurrence while not excluding excessive numbers of patients from candidacy. Existing criteria are challenged by the limited accuracy of radiological assessment. The total tumor volume (TTV) was calculated by the addition of the volume of each individual tumor. A preliminary analysis was carried out on HCC patient data from the Alberta Liver Transplant Program (52 patients) and then validated on the populations of the Universities of Toronto and Colorado programs (154 and 82 patients). A TTV cutoff of 115 cm(3) was chosen on the basis of the risk of recurrence with use of a receiver operating characteristic curve. Radiology correlated more closely to pathology with TTV than with Milan and University of California at San Francisco (UCSF) criteria (91% versus 69% and 75% of patients, P < 0.0001). Although more patients met qualifying criteria for transplant with TTV (28%-53% more than Milan and 16%-26% more than UCSF), no deterioration of outcome was demonstrated in an analysis of patients within TTV ≤ 115 cm(3) in comparison with those meeting Milan or UCSF classifications at all institutions. Patients with TTV > 115 cm(3) experienced more recurrences and lower patient survival in the Alberta and Colorado series (P < 0.05). When TTV with a cutoff of 115 cm(3) is used for candidate selection, the accuracy of pretransplant radiological assessment is enhanced, with posttransplant outcomes not different from those achieved with Milan and UCSF classifications despite a more inclusive patient population.

Background Tumor recurrence remains the major cause of death after curative resection for hepatocellular carcinoma (HCC). The purpose of this study was to identify risk factors for the recurrence of HCC and to examine long-term outcomes after resection. Methods From July 1992 to July 2004, 193 consecutive patients who underwent hepatic resection as primary therapy with curative intent for HCC were included in this single-center analysis. The perioperative mortality rate was 5%. Time to recurrence (disease-free survival) and overall survival were determined by Kaplan-Meier analysis. Demographic, tumor, and treatment characteristics were tested for their prognostic significance by univariate and multivariate analysis with the log-rank test and the Cox proportional hazards model, respectively. Results Median overall survival for the entire cohort was 71 ± 11 months; disease-free survival was 34 months (range, 1-149 months). After a median follow-up time of 34 months, 98 patients (51%) experienced recurrent cancer; initial tumor recurrence was confined to the liver in 86 patients (88%). With the use of multivariate analysis, preoperative vascular invasion detected on radiologic imaging studies; postoperative vascular invasion found on pathologic assessment, and intermediate and poor tumor differentiation and tumor size and number were significant predictors of disease-free survival. Of the 98 patients who had tumor recurrence, 53 patients (54%) underwent additional therapy (ablation, 31 patients; re-resection, 11 patients; transarterial chemoembolization, 8 patients; liver transplantation, 3 patients) with improvement in survival. Conclusion Despite recurrences in >50% of patients, long-term survival can be achieved after resection of HCC. Identification of risk factors, close follow-up evaluation, and early detection are mandatory because recurrences that are confined to the liver may be amenable to treatment with an additional survival benefit.

Many centers are reluctant to use older donors (44 years) for adult right-lobe living donor liver transplantation (RLDLT) due to concerns about possible increased morbidity in donors and poorer outcomes in recipients. Since 2000, 130 adult RLDLTs have been performed at our institution. Recipients were divided into those who received a right lobe graft from a donor/=age 44 (n = 89, 68%; median age 30) and those who received a liver graft from a donor age44 (n = 41, 32%; mean age 52). The two donor and recipient populations had similar demographic and operative profiles. With a median follow-up of 29 months, the severity and number of complications in older donors were similar to those in younger donors. No living donor died. Older donor allografts had initial allograft dysfunction compared to younger donors. Complication rates were similar among recipients in both groups but there was a higher bile duct stricture rate with older donor grafts (27% vs. 12%; p = 0.04). One-year recipient graft survival was 86% for older donors and 85% for younger donors (p = 0.95). Early experience with the use of selected older adults (44 years) for RLDLT is encouraging, but may be associated with a higher rate of biliary complications in the recipient.

Biliary strictures remain the most challenging aspect of adult right lobe living donor liver transplantation (RLDLT). Between 04/2000 and 10/2005, 130 consecutive RLDLTs were performed in our center and followed prospectively. Median follow-up was 23 months (range 3-67) and 1-year graft and patient survival was 85% and 87%, respectively. Overall incidence of biliary leaks (n = 19) or strictures (n = 22) was 32% (41/128) in 33 patients (26%). A duct-to-duct (D-D) or Roux-en-Y (R-Y) anastomosis were performed equally (n = 64 each) with no difference in stricture rate (p = 0.31). The use of ductoplasty increased the number of grafts with a single duct for anastomosis and reduced the biliary complication rate compared to grafts/=2 ducts (17% vs. 46%; p = 0.02). Independent risk factors for strictures included older donor age and previous history of a bile leak. All strictures were managed nonsurgically initially but four patients ultimately required conversion from D-D to R-Y. Ninety-six percent (123/128) of patients are currently free of any biliary complications. D-D anastomosis is safe after RLDLT and provides access for future endoscopic therapy in cases of leak or stricture. When presented with multiple bile ducts, ductoplasty should be considered to reduce the potential chance of stricture.