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Background: Existing research exploring predictors of success on American Board of Surgery (ABS) exams focused on either resident or residency program characteristics, but limited studies focus on both. This study examines relationships between both resident and program characteristics and ABS Qualifying (QE) and Certifying Exam (CE) outcomes., Study Design: Multilevel logistic regression was used to analyze the relationship between resident and program characteristics and ABS QE and CE 1st attempt pass and eventual certification. Resident characteristics were gender, IMG status, and prior performance, measured by 1st attempt USMLE Step 2 CK and Step 3 scaled scores. Program characteristics were size, %female, %International Medical Graduate (IMG), and program type. The sample included surgeons with QE and CE data from 2007-2019 and matched USMLE scores., Results: Controlling for other variables, prior medical performance positively related to all ABS exam outcomes. The relationships between USMLE scores and success on ABS exams varied but were generally strong. Other resident characteristics that predicted ABS exam outcomes were gender and IMG (QE 1st attempt pass). The only program characteristic that significantly predicted ABS outcomes was %IMG (QE and CE 1st attempt pass). Despite statistical significance, gender, IMG, and %IMG translated to small differences in predicted probabilities of ABS exam success., Conclusion: This study highlights resident and program characteristics that predict success on ABS exams. USMLE scores consistently and strongly related to ABS exam success, providing evidence that USMLE scores relate to future high-stakes consequences like board certification. After controlling for prior performance, gender, IMG, and program %IMG significantly related to ABS exam success, but effects were small., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Liver transplant (LT) using organs donated after circulatory death (DCD) has been increasing in the United States. We investigated whether transplant centers' receptiveness to use of DCD organs impacted patient outcomes., Methods: Transplant centers were classified as very receptive (group 1), receptive (2), or less receptive (3) based on the DCD acceptance rate and DCD transplant percentage. Using organ procurement and transplantation network/UNOS registry data for 20 435 patients listed for LT from January 2020 to June 2022, we compared rates of 1-y transplant probability and waitlist mortality between groups, broken down by model for end-stage liver disease-sodium (MELD-Na) categories., Results: In adjusted analyses, patients in group 1 centers with MELD-Na scores 6 to 29 were significantly more likely to undergo transplant than those in group 3 (aHR range 1.51-2.11, P  < 0.001). Results were similar in comparisons between groups 1 and 2 (aHR range 1.41-1.81, P  < 0.001) and between groups 2 and 3 with MELD-Na 15-24 (aHR 1.19-1.20, P  < 0.007). Likewise, patients with MELD-Na score 20 to 29 in group 1 centers had lower waitlist mortality than those in group 3 (scores, 20-24: aHR, 0.71, P  = 0.03; score, 25-29: aHR, 0.51, P  < 0.001); those in group 1 also had lower waitlist mortality compared with group 2 (scores 20-24: aHR0.69, P  = 0.02; scores 25-29: aHR 0.63, P  = 0.03). One-year posttransplant survival of DCD LT patients did not vary significantly compared with donation after brain dead., Conclusions: We conclude that transplant centers' use of DCD livers can improve waitlist outcomes, particularly among mid-MELD-Na patients., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: A new liver allocation policy was implemented by United Network for Organ Sharing (UNOS) in February 2020 with the stated intent of improving access to liver transplant (LT). There are growing concerns nationally regarding the implications this new system may have on LT costs, as well as access to a chance for LT, which have not been captured at a multicenter level., Objective: To characterize LT volume and cost changes across the US and within specific center groups and demographics after the policy implementation., Design, Setting, and Participants: This cross-sectional study collected and reviewed LT volume from multiple centers across the US and cost data with attention to 8 specific center demographics. Two separate 12-month eras were compared, before and after the new UNOS allocation policy: March 4, 2019, to March 4, 2020, and March 5, 2020, to March 5, 2021. Data analysis was performed from May to December 2022., Main Outcomes and Measures: Center volume, changes in cost., Results: A total of 22 of 68 centers responded comparing 1948 LTs before the policy change and 1837 LTs postpolicy, resulting in a 6% volume decrease. Transplants using local donations after brain death decreased 54% (P < .001) while imported donations after brain death increased 133% (P = .003). Imported fly-outs and dry runs increased 163% (median, 19; range, 1-75, vs 50, range, 2-91; P = .009) and 33% (median, 3; range, 0-16, vs 7, range, 0-24; P = .02). Overall hospital costs increased 10.9% to a total of $46 360 176 (P = .94) for participating centers. There was a 77% fly-out cost increase postpolicy ($10 600 234; P = .03). On subanalysis, centers with decreased LT volume postpolicy observed higher overall hospital costs ($41 720 365; P = .048), and specifically, a 122% cost increase for liver imports ($6 508 480; P = .002). Transplant centers from low-income states showed a significant increase in hospital (12%) and import (94%) costs. Centers serving populations with larger proportions of racial and ethnic minority candidates and specifically Black candidates significantly increased costs by more than 90% for imported livers, fly-outs, and dry runs despite lower LT volume. Similarly, costs increased significantly (>100%) for fly-outs and dry runs in centers from worse-performing health systems., Conclusions and Relevance: Based on this large multicenter effort and contrary to current assumptions, the new liver distribution system appears to place a disproportionate burden on populations of the current LT community who already experience disparities in health care. The continuous allocation policies being promoted by UNOS could make the situation even worse.

Background: In 2019, Organ Procurement and Transplantation Network/United Network for Organ Sharing changed the exception policy for liver allocation to the median model for end-stage liver disease at transplantation (MMaT). This study evaluated the effects of this change on-waitlist outcomes of simultaneous liver-kidney transplantation (SLKT) for patients with polycystic liver-kidney disease (PLKD)., Methods: Using the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry, 317 patients with PLKD listed for SLKT between January 2016 and December 2021 were evaluated. Waitlist outcomes were compared between prepolicy (Era 1) and postpolicy (Era 2) eras., Results: One-year transplant probability was significantly higher in Era 2 than in Era 1 (55.7% versus 37.9%; P  = 0.001), and the positive effect on transplant probability of Era 2 was significant after risk adjustment (adjusted hazard ratio, 1.76; 95% confidence interval, 1.22-2.54; P  = 0.002 [ref. Era 1]), whereas waitlist mortality was comparable. Transplant centers were separated into the high and low MMaT groups with a score of 29 (median MMaT) and transplant probability in each group between eras was compared. In the high MMaT transplant centers, the 1-y transplant probability was significantly higher in Era 2 (27.5% versus 52.4%; P  = 0.003). The positive effect remained significant in the high MMaT center group (adjusted hazard ratio, 2.79; 95% confidence interval, 1.43-5.46; P  = 0.003 [ref. Era 1]) but not in the low MMaT center group. Although there was a difference between center groups in Era 1 ( P  = 0.006), it became comparable in Era 2 ( P  = 0.54)., Conclusions: The new policy increased 1-y SLKT probability in patients with PKLD and successfully reduced the disparities based on center location., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although transfusion management has improved during the last decade, orthotopic liver transplantation (OLT) has been associated with considerable blood transfusion requirements which poses some challenges in securing blood bank inventories. Defining the predictors of massive blood transfusion before surgery will allow the blood bank to better manage patients' needs without delays. We evaluated the predictors of intraoperative massive transfusion in OLT., Study Design and Methods: Data were collected on patients who underwent OLT between 2007 and 2017. Repeat OLTs were excluded. Analyzed variables included recipients' demographic and pretransplant laboratory variables, donors' data, and intraoperative variables. Massive transfusion was defined as intraoperative transfusion of ≥10 units of packed red blood cells (RBCs). Statistical analysis was performed using SPSS version 17.0., Results: The study included 970 OLT patients. The median age of patients was 57 (range: 16-74) years; 609 (62.7%) were male. RBCs, thawed plasma, and platelets were transfused intraoperatively to 782 (80.6%) patients, 831 (85.7%) patients, and 422 (43.5%) patients, respectively. Massive transfusion was documented in 119 (12.3%) patients. In multivariate analysis, previous right abdominal surgery, the recipient's hemoglobin, Model for End Stage Liver Disease (MELD) score, cold ischemia time, warm ischemia time, and operation time were predictive of massive transfusion. There was a direct significant correlation between the number of RBC units transfused and plasma (Pearson correlation coefficient r = .794) and platelets (r = .65)., Discussion: Previous abdominal surgery, the recipient's hemoglobin, MELD score, cold ischemia time, warm ischemia time, and operation time were predictive of intraoperative massive transfusion in OLT., (© 2023 AABB.)

Absolute lymphocyte count (ALC) is considered a surrogate marker for nutritional status and immunocompetence. We investigated the association between ALC and post-liver transplant outcomes in patients who received a deceased donor liver transplant (DDLT). Patients were categorized by ALC at liver transplant: low (<500/μL), mid (500-1000/μL), and high ALC (>1000/μL). Our main analysis used retrospective data (2013-2018) for DDLT recipients from Henry Ford Hospital (United States); the results were further validated using data from the Toronto General Hospital (Canada). Among 449 DDLT recipients, the low ALC group demonstrated higher 180-day mortality than mid and high ALC groups (83.1% vs 95.8% and 97.4%, respectively; low vs mid: P = .001; low vs high: P < .001). A larger proportion of patients with low ALC died of sepsis compared with the combined mid/high groups (9.1% vs 0.8%; P < .001). In multivariable analysis, pretransplant ALC was associated with 180-day mortality (hazard ratio, 0.20; P = .004). Patients with low ALC had higher rates of bacteremia (22.7% vs 8.1%; P < .001) and cytomegaloviremia (15.2% vs 6.8%; P = .03) than patients with mid/high ALC. Low ALC pretransplant through postoperative day 30 was associated with 180-day mortality among patients who received rabbit antithymocyte globulin induction (P = .001). Pretransplant lymphopenia is associated with short-term mortality and a higher incidence of posttransplant infections in DDLT patients., (Copyright © 2022. Published by Elsevier Inc.)

Background and Objectives: D-negative patients undergoing orthotopic liver transplantation (OLT) might require a large number of red blood cell (RBC) units, which can impact the inventory of D-negative blood. The blood bank might need to supply these patients with D-positive RBCs because of inventory constraints. This study evaluates the prevalence of anti-D formation in D-negative OLT patients who received D-positive RBCs perioperatively, as this will assist in successful patient blood management., Materials and Methods: This was a retrospective study performed at a single academic medical centre. Electronic medical records for all 1052 consecutive patients who underwent OLT from January 2007 through December 2017 were reviewed. D-negative patients who were transfused perioperatively with D-positive RBCs and had antibody screening at least 30 days after transfusion were included., Results: Of a total of 155 D-negative patients, 23 (14.8%) received D-positive RBCs perioperatively. Seventeen patients were included in the study. The median age was 54 years (range 36-67 years); 13 (76.5%) were male. The median number of D-positive RBC units transfused perioperatively was 7 (range 1-66 units). There was no evidence of D alloimmunization in any patient after a median serologic follow-up of 49.5 months (range 31 days to 127.7 months). The average number of antibody screening post OLT was 7.29., Conclusion: Our study showed that transfusion of D-positive RBCs in D-negative OLT recipients is a safe and acceptable practice in the setting of immunosuppression. This practice allows the conservation of D-negative RBC inventory., (© 2022 International Society of Blood Transfusion.)

Importance: Ischemic cold storage (ICS) of livers for transplant is associated with serious posttransplant complications and underuse of liver allografts., Objective: To determine whether portable normothermic machine perfusion preservation of livers obtained from deceased donors using the Organ Care System (OCS) Liver ameliorates early allograft dysfunction (EAD) and ischemic biliary complications (IBCs)., Design, Setting, and Participants: This multicenter randomized clinical trial (International Randomized Trial to Evaluate the Effectiveness of the Portable Organ Care System Liver for Preserving and Assessing Donor Livers for Transplantation) was conducted between November 2016 and October 2019 at 20 US liver transplant programs. The trial compared outcomes for 300 recipients of livers preserved using either OCS (n = 153) or ICS (n = 147). Participants were actively listed for liver transplant on the United Network of Organ Sharing national waiting list., Interventions: Transplants were performed for recipients randomly assigned to receive donor livers preserved by either conventional ICS or the OCS Liver initiated at the donor hospital., Main Outcomes and Measures: The primary effectiveness end point was incidence of EAD. Secondary end points included OCS Liver ex vivo assessment capability of donor allografts, extent of reperfusion syndrome, incidence of IBC at 6 and 12 months, and overall recipient survival after transplant. The primary safety end point was the number of liver graft-related severe adverse events within 30 days after transplant., Results: Of 293 patients in the per-protocol population, the primary analysis population for effectiveness, 151 were in the OCS Liver group (mean [SD] age, 57.1 [10.3] years; 102 [67%] men), and 142 were in the ICS group (mean SD age, 58.6 [10.0] years; 100 [68%] men). The primary effectiveness end point was met by a significant decrease in EAD (27 of 150 [18%] vs 44 of 141 [31%]; P = .01). The OCS Liver preserved livers had significant reduction in histopathologic evidence of ischemia-reperfusion injury after reperfusion (eg, less moderate to severe lobular inflammation: 9 of 150 [6%] for OCS Liver vs 18 of 141 [13%] for ICS; P = .004). The OCS Liver resulted in significantly higher use of livers from donors after cardiac death (28 of 55 [51%] for the OCS Liver vs 13 of 51 [26%] for ICS; P = .007). The OCS Liver was also associated with significant reduction in incidence of IBC 6 months (1.3% vs 8.5%; P = .02) and 12 months (2.6% vs 9.9%; P = .02) after transplant., Conclusions and Relevance: This multicenter randomized clinical trial provides the first indication, to our knowledge, that normothermic machine perfusion preservation of deceased donor livers reduces both posttransplant EAD and IBC. Use of the OCS Liver also resulted in increased use of livers from donors after cardiac death. Together these findings indicate that OCS Liver preservation is associated with superior posttransplant outcomes and increased donor liver use., Trial Registration: ClinicalTrials.gov Identifier: NCT02522871.

Background and Objectives: Orthotopic liver transplantation (OLT) has been associated with high blood transfusion requirements. We evaluated the transfusion needs and frequency of alloimmunization to RBC antigens among OLT recipients pre- and post-transplantation., Materials and Methods: We reviewed the medical records of patients who underwent a first OLT between January 2007 and June 2017. Transfusions given only during the perioperative period, defined by 1 week before OLT until 2 weeks following OLT, were included in this study. Records were reviewed in June 2019 for updated antibody testing results., Results: A total of 970 patients underwent OLT during the study period. The median age of patients was 57 years; 608(62.7%) were male. During the perioperative period, transfused patients received an average of 10.7 (±10.7) RBC units, 15.6 (±16.2) thawed plasma units and 4.1 (±4.3) platelet units. At the time of OLT, a total of 101 clinically significant RBC alloantibodies were documented in 58(5.98%) patients. Fifty-three of these antibodies were directed against Rh blood group antigens. Twenty-two (37.9%) patients had more than one alloantibody. Patients with alloimmunization before OLT (N = 58) received perioperatively comparable number of RBCs to non-alloimmunized patients (10.5 ± 10.6 vs. 9.6 ± 10.7; p = 0.52). There was no significant difference in perioperative or intraoperative RBC transfusion between patients with one alloantibody and those with multiple alloantibodies. Only 16 patients (16/737; 2.17%) developed new alloantibodies at a median of 61 days after OLT. The overall alloimmunization rate was 9.8% (72/737), and female patients were more likely to be alloimmunized., Conclusion: Blood transfusion requirements in OLT remain high. However, the rate of RBC alloimmunization was not higher than the general patient population., (© 2021 International Society of Blood Transfusion.)

Use of higher-risk grafts in liver transplantation for patients with acute-on-chronic liver failure (ACLF) has been associated with poor outcomes. This study analyzes trends in liver transplantation outcomes for ACLF over time based on the donor risk index (DRI)., Methods: Using the Organ Procurement and Transplantation Network and the United Network for Organ Sharing registry, 17 300 ACLF patients who underwent liver transplantation between 2002 and 2019 were evaluated. Based on DRI, adjusted hazard ratios for 1-y patient death were analyzed in 3 eras: Era 1 (2002-2007, n = 4032), Era 2 (2008-2013, n = 6130), and Era 3 (2014-2019, n = 7138). DRI groups were defined by DRI <1.2, 1.2-1.6, 1.6-2.0, and >2.0., Results: ACLF patients had significantly lower risks of patient death within 1 y in Era 2 (adjusted hazard ratio, 0.69; 95% confidence interval, 0.61-0.78; P < 0.001) and Era 3 (adjusted hazard ratio, 0.48; 95% confidence interval, 0.42-0.55; P < 0.001) than in Era 1. All DRI groups showed lower hazards in Era 3 than in Era 1. Improvement of posttransplant outcomes were found both in ACLF-1/2 and ACLF-3 patients. In ACLF-1/2, DRI 1.2 to 1.6 and >2.0 had lower adjusted risk in Era 3 than in Era 1. In ACLF-3, DRI 1.2 to 2.0 had lower risk in Era 3. In the overall ACLF cohort, the 2 categories with DRI >1.6 had significantly higher adjusted risks of 1-y patient death than DRI <1.2. When analyzing hazards in each era, DRI > 2.0 carried significantly higher adjusted risks in Eras 1 and 3' whereas DRI 1.2 to 2.0 had similar adjusted risks throughout eras. Similar tendency was found in ACLF-1/2. In the non-ACLF cohort, steady improvement of posttransplant outcomes was obtained in all DRI categories. Similar results were obtained when only hepatitis C virus-uninfected ACLF patients were evaluated., Conclusions: In ACLF patients, posttransplant outcomes have significantly improved, and outcomes with higher-risk organs have improved in all ACLF grades. These results might encourage the use of higher-risk donors in ACLF patients and provide improved access to transplant., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Graft-versus-host disease (GVHD) after liver transplantation (LT) is a rare but serious complication. The aim of this study is to identify risk factors, including immunosuppressive regimens, for mortality due to GVHD (fatal GVHD)., Methods: Using data from the Organ Procurement and Transplantation Network and United Network for Organ Sharing registry, 77 416 adult patients who underwent LT between 2003 and 2018 were assessed. Risk factors for fatal GVHD were analyzed by focusing on induction and maintenance immunosuppression regimens., Results: The incidence of fatal GVHD was 0.2% (121 of 77 416), of whom 105 (87%) died within 180 d and 13 (11%) died between 181 d and 1 y. Median survival after LT was 68.0 (49.5-125.5) d. Recipient age minus donor age >20 y (hazard ratio [HR], 2.57; P < 0.001) and basiliximab induction (HR, 1.69; P = 0.018) were independent risk factors for fatal GVHD. Maintenance therapy with mycophenolate mofetil (MMF) was associated with a decrease in fatal GVHD (HR, 0.51; P = 0.001). In an increased risk cohort of patients with recipient-donor age discrepancy >20 y, MMF use was associated with a 50% decline in fatal GVHD (HR, 0.50; P < 0.001)., Conclusions: Recipient age minus donor age >20 y remains a significant risk factor for fatal GVHD. The risk of fatal GVHD significantly increases in association with basiliximab induction and decreases with MMF maintenance. These associations were pronounced in patients with recipient minus donor age >20 y. These results emphasize the importance of donor age and individualized immunosuppression regimens on the risk of fatal GVHD., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Although recent studies have reported favorable outcomes in living donor liver transplantation (LDLT), it remains unclear which populations benefit most from LDLT. This study aims to evaluate LDLT outcomes compared with deceased donor LT (DDLT) according to Model for End-Stage Liver Disease (MELD) score categories. Using data from the United Network for Organ Sharing registry, outcomes were compared between 1486 LDLTs; 13,568 donation after brain death (DBD)-DDLTs; and 1171 donation after circulatory death (DCD)-DDLTs between 2009 and 2018. Because LDLT for patients with MELD scores >30 was rare, all patients with scores >30 were excluded to equalize LDLT and DDLT cohorts. Risk factors for 1-year graft loss (GL) were determined separately for LDLT and DDLT. Compared with LDLT, DBD-DDLT had a lower risk of 30-day (adjusted hazard ratio [aHR], 0.60; P < 0.001) and 1-year GL (aHR, 0.57; P < 0.001). The lower risk of GL was more prominent in the mid-MELD score category (score 15-29). Compared with LDLT, DCD-DDLT had a lower risk of 30-day GL but a comparable risk of 1-year GL, regardless of MELD score category. In LDLT, significant ascites was an independent risk for GL in patients with mid-MELD scores (aHR, 1.68; P = 0.02), but not in the lower-MELD score group. The risk of 1-year GL in LDLT patients with ascites who received a left liver was higher than either those who received a right liver or those without ascites who received a left liver. In LDLT, combinations of MELD scores of 15 to 29, moderate/severe ascites, and the use of a left liver are associated with worse outcomes. These findings help calibrate appropriate patient and graft selection in LDLT., (Copyright © 2021 by the American Association for the Study of Liver Diseases.)

Islet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and "more than minimally manipulated" human cell and tissue products (HCT/Ps). In contrast, across the world, human islets are appropriately defined as "minimally manipulated tissue" and not regulated as a drug, which has led to islet allotransplantation (allo-ITx) becoming a standard-of-care procedure for selected patients with type 1 diabetes mellitus. This regulatory distinction impedes patient access to islets for transplantation in the US. As a result only 11 patients underwent allo-ITx in the US between 2016 and 2019, and all as investigational procedures in the settings of a clinical trials. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Based on favorable outcomes reported by experienced centers, perihilar cholangiocarcinoma (Ph-CCA) has become an accepted indication for liver transplantation (LT). What is less clear is if the reported outcomes have been reproduced nationwide in the US., Objective: The aim of this study was to evaluate post-transplant outcomes in patients with Ph-CCA and to determine prognostic factors., Methods: Patients who underwent LT with Model for End-stage Liver Disease exception scores for Ph-CCA between 2010 and 2017 were evaluated. Transplant centers were classified into well- and less-experienced groups: Group 1 [well-experienced (≥ 6 LTs), 7 centers]; Group 2 [less-experienced (< 6 LTs), 23 centers]. Post-transplant mortality due to all-cause and recurrence of Ph-CCA were set as endpoints., Results: Post-transplant outcomes were significantly better in Group 1 than in Group 2, with 1-, 3-, and 5-year patient survival rates of 91.8%, 56.9%, and 45.8%, versus 65.6%, 48.8%, and 26.0%, respectively. Group 2 showed a significantly higher risk of 1-, 3-, and 5-year all-cause mortality and 1-year mortality associated with Ph-CCA recurrence. Center experience was an independent risk factor for post-transplant mortality. In intention-to-treat analysis, a positive prognostic effect of LT was significant and LT decreased the mortality risk by 86% in the well-experienced group [hazard ratio (HR) 0.14, p < 0.001], whereas this effect was not observed in the less-experienced group (HR 1.35, p = 0.47)., Conclusions: Risk of recurrence of malignancy and mortality was significantly higher in the less-experienced center group. Center effects on post-transplant outcomes in patients with Ph-CCA should be recognized, and the introduction of center approval for LT for Ph-CCA may be justified to achieve comparable outcomes between centers.

Background and Aims: Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) policy mandates a 6-month waiting period before exception scores are granted to liver transplant candidates with hepatocellular carcinoma (HCC). This study aims to evaluate waitlist and posttransplant outcomes in patients with HCC, before and after implementation of the 6-month waiting rule., Approach and Results: We examined two groups from the UNOS registry: Group 1 (pre-6-month rule) consisted of patients registered as transplant candidates with HCC from January 1, 2013, to October 7, 2015 (n = 4,814); group 2 (post-6-month rule) consisted of patients registered from October 8, 2015, to June 30, 2018 (n = 3,287). As expected, the transplant probability was higher in the first 6 months after listing in group 1 than group 2 at 42.0% versus 6.3% (P < 0.001). However, the 6-month waitlist mortality/dropout rate was lower in group 2 at 1.2% than group 1 at 4.1% (P < 0.001). To assess regional parity of transplant, UNOS regions were categorized into three groups based on Model for End-Stage Liver Disease score at transplant: lower-score (regions 3, 10, and 11), middle-score (1, 2, 6, 8, and 9), and higher-score region groups (4, 5, and 7). Outcomes were compared from the time exception points were given, which we defined as conditional waitlist outcomes. Conditional waitlist mortality/dropout decreased, and transplant probability increased in all region groups, but the benefits of the policy were more pronounced in the higher and middle-score groups, compared with the lower-score group. The decline in waitlist mortality/dropout was only significant in the high Model for End-Stage Liver Disease group (P < 0.001). No effect was observed on posttransplant mortality or percent of patients within Milan criteria on explant., Conclusions: The HCC policy change was associated with decreased waitlist mortality/dropout and increased transplant probability. The policy helped to decrease but did not eliminate regional disparities in transplant opportunity without an effect on posttransplant outcomes., (© 2020 by the American Association for the Study of Liver Diseases.)

With the introduction of Model for End-Stage Liver Disease-Sodium (MELD-Na)-based allocation, the score at which patients benefit from liver transplantation (LT) has shifted from a score of 15 to 21. This study aimed to evaluate waitlist outcomes in patients with MELD-Na scores <21 and explore the utility of replacing "Share 15" with "Share 21." The study uses data from the Organ Procurement and Transplantation Network/United Network for Organ Sharing registry. All adult patients registered for LT after implementation of the MELD-Na-based allocation were evaluated. Waitlist patients with initial and final scores <21 were eligible. Patients with exception scores were excluded. To explore the potential impact of a Share 21 model, patients with an initial MELD-Na score of 6-14 (Group 1) and those with a score of 15-20 (Group 2) were compared for waitlist outcomes. There were 3686 patients with an initial score of 6-14 (Group 1) and 3282 with a score of 15-20 (Group 2). Group 2, when compared to Group 1, showed comparable risk of mortality (adjusted hazard ratio [aHR] 1.00, P = .97), higher transplant probability (aHR 3.25, P < .001), and lower likelihood of removal from listing because of improvement (aHR 0.74, P = .011). Share 21 may enhance transplant opportunities and increase parity for patients with higher MELD-Na scores without compromising waitlist outcomes., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

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There is growing interest in performing liver transplantation (LT) in patients with alcoholic hepatitis (AH) without a mandated abstinence period. The aim of this study is to investigate waitlist outcomes in AH patients compared to those with other liver diseases. Using data from the UNOS registry, adult patients listed for LT between 2009 and 2018 were evaluated. Waitlist outcomes were compared among liver diseases. A total of 64 646 patients were eligible, including 286 with AH, 16 871 with alcoholic cirrhosis (AC), 13 730 with hepatitis C (HCV), 10 315 with non-alcoholic steatohepatitis (NASH), and 5841 with cholestatic liver disease (CLD). In comparison with AH patients, patients with HCV, NASH, and CLD had a significantly higher risk of waitlist mortality and a lower likelihood of recovery on the waitlist. These trends were more prominent in the waiting-time period of 91-365 days than in shorter periods. In intention-to-treat analysis, positive prognostic effect of LT was significant in AH patients with MELD score ≥35 (HR 0.04, P < .001). AH patients showed lower mortality risk and a higher chance of recovery while on waitlist than other liver diseases, especially when waiting time exceeded 90 days. These results indicate the importance of continuous evaluation of disease progression in AH patients awaiting LT., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Alcohol relapse after liver transplantation (LT) in patients with alcohol-related liver disease (ALD) is a major challenge. Although its association with pretransplant psychosocial factors was extensively studied, the impacts of posttransplant courses on alcohol relapse have not been well investigated. The aim of this study is to analyze peritransplant factors associated with posttransplant alcohol relapse in patients with ALD. This study evaluated 190 adult LT patients with ALD from 2013 to 2019. Risk factors for alcohol relapse were analyzed, focusing on posttransplant chronic complications, which were classified as Clavien-Dindo classification 3a or higher that lasted over 30 days. The posttransplant alcohol relapse rate was 13.7% (26/190) with a median onset time of 18.6 months after transplant. Multivariate Cox regression analysis revealed that posttransplant chronic complications were an independent risk factor for posttransplant alcohol relapse (hazard ratio [HR], 5.40; P = 0.001), along with psychiatric comorbidity (HR, 3.93; P = 0.001), history of alcohol relapse before LT (HR, 3.00; P = 0.008), and an abstinence period <1.5 years (HR, 12.05; P = 0.001). A risk prediction model was created using 3 pretransplant risk factors (psychiatric comorbidity, alcohol relapse before LT, and abstinence period <1.5 years). This model clearly stratified the risk of alcohol relapse into high-, moderate-, and low-risk groups (P < 0.001). Of the 26 patients who relapsed, 11 (42.3%) continued drinking, of whom 3 died of severe alcoholic hepatitis, and 13 (50.0%) achieved sobriety (outcomes for 2 patients were unknown). In conclusion, posttransplant chronic complications increased the risk of alcohol relapse. Recognition of posttransplant chronic complications in conjunction with the risk stratification model by pretransplant psychosocial factors would help with the prediction of posttransplant alcohol relapse., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Background & Aims: An increasing number of patients with non-alcoholic steatohepatitis (NASH) require liver transplantation. We compared outcomes of patients with liver diseases of different etiologies (NASH, hepatitis C virus [HCV]-associated liver disease, and alcohol-associated liver disease [ALD])., Methods: We analyzed data from the United Network for Organ Sharing registry on 6344 patients who underwent liver transplantation for NASH, 17,037 for cirrhosis from chronic HCV infection, and 9279 for ALD. We collected data from patients who underwent liver transplantation during the following time periods: 2008-2010, 2011-2013, 2014-2015, 2016-2017. We compared outcomes of different groups using Cox regression models, adjusting for donor and recipient characteristics., Results: For patients who underwent liver transplantation during 2016-2017, a significantly lower proportion of patients with NASH survived for 1 year after transplantation than patients with HCV (P = .004) or ALD (P < .001). During this time period, the adjusted risk of death within 1 year was significantly higher for patients with NASH than with ALD (hazard ratio, 1.37; P = .03), regardless of the presence of hepatocellular carcinoma. The effects of increasing age were greatest among patients with NASH: compared to patients younger than 50 years, hazard ratios for overall mortality were 1.31 for patients 50-59 years (P = .02), 1.66 for patients 60-64 years (P < .001), 2.08 for patients 65-69 years (P < .001), and 2.66 and for patients and ≥70 years (P < .001). Mortality from cardiovascular or cerebrovascular disease(s) was highest among patients with NASH, accounting for 11.5% of deaths, compared to 7.0% of deaths in patients with HCV infection and 9.6% in patients with ALD (P < .001)., Conclusions: In an analysis of data from patients who underwent liver transplantation during 2016-2017, we found the risk of death within 1 year after transplant was higher among patients with NASH than HCV-associated liver disease or ALD. Risk of death increased with age, and patients with NASH have a higher risk of death from cardiovascular or cerebrovascular disease., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Appropriate graft regeneration after living donor liver transplantation (LDLT) is crucial to avoid small-for-size syndrome. We enrolled 44 recipients who underwent ABO-identical/compatible LDLT from December 2007 to August 2016 and determined possible factors associated with low graft regeneration after LDLT. Liver regeneration was calculated by the ratio of the graft size on postoperative day (POD) 7 ± 1 day (calculated by CT volumetry) to the size of the donated liver at implant. Postoperative outcomes were compared between the low and high regeneration groups. Median regeneration rate was 1.65-fold. Regeneration rate was negatively correlated with graft-to-recipient weight ratio. Postoperative morbidity rates on POD 14-90 were significantly higher in the low group compared with the high group (63% vs 18%, P = .03). Graft and patient survival in the low group were significantly worse than the high group (1-year graft survival 73% vs 100%, P = .002; patient survival 82% vs 100%, P = .01). Cold ischemia time (CIT; per 10 minute; odds ratio [OR] =1.37) and platelet count <60 000/μL on POD 5 (OR = 14.32) were independently associated with low regeneration. In conclusion, longer CIT and postoperative thrombocytopenia were associated with low graft regeneration in the early phase after LDLT, which could consequently lead to poor graft and patient survival., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study aimed to investigate risk factors for early allograft dysfunction (EAD) and outcomes after liver transplantation (LT), focusing on peri-transplant lactate clearance. We reviewed patients who underwent deceased donor LTs between 2011 and 2014. Lactate levels were checked at reperfusion and at the time of intensive care unit admission. Early lactate clearance was defined as reduction rate of lactate between the times of reperfusion and immediately after LT. Patients were categorized into the normal and delayed clearance groups. We used propensity score matching (PSM) between these two groups to estimate an impact of lactate clearance on incidence of EAD and graft survival. A total of 256 recipients were eligible for this study. Cut-off value of lactate clearance to predict occurrence of EAD was determined at 0.2 mmol/L/h. After PSM, 120 patients in the normal clearance and 36 patients in the delayed clearance group were matched. Delayed lactate clearance was considered as an independent risk factor for EAD (Odds ratio 3.49, P = 0.002). The adjusted hazard of one-year graft loss was significantly increased in the delayed clearance group (hazard ratio 6.69, P = 0.001). In conclusion, peri-transplant delayed lactate clearance may be a strong predictor for EAD and poor liver graft outcomes., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: The Model for End-stage Liver Disease and Sodium (MELD-Na) score was introduced for liver allocation in January 2016. We evaluated the effects of liver allocation, based on MELD-Na score, on waitlist and post-transplantation outcomes., Methods: We examined 2 patient groups from the United Network for Organ Sharing registry; the MELD-period group was composed of patients who were registered as transplant candidates from June 18, 2013 through January 10, 2016 (n = 18,850) and the MELD-Na period group was composed of patients who were registered from January 11, 2016 through September 30, 2017 (n = 14,512). We compared waitlist and post-transplantation outcomes and association with serum sodium concentrations between groups., Results: Mortality within 90 days on the liver waitlist decreased (hazard ratio [HR] 0.738, P < .001) and transplantation probability increased significantly (HR 1.217, P < .001) in the MELD-Na period. Although mild, moderate, and severe hyponatremia (130-134, 125-129, and <125 mmol/L) were independent risk factors for waitlist mortality in the MELD period (HR 1.354, 1.762, and 2.656; P < .001, P < .001, and P < .001, respectively) compared with the reference standard (135-145 mmol/L), these adverse outcomes were decreased in the MELD-Na period (HR 1.092, 1.271 and 1.374; P = .27, P = .018, and P = .037, respectively). The adjusted survival benefit of transplant recipients vs patients placed on the waitlist in the same score categories was definitive for patients with MELD-Na scores of 21-23 in the MELD-Na era (HR 0.336, P < .001) compared with MELD scores of 15-17 in the MELD era (HR 0.365, P < .001)., Conclusions: Liver allocation based on MELD-Na score successfully improved waitlist outcomes and provided significant benefit to hyponatremic patients. Given the discrepancy in transplantation survival benefit, the current rules for liver allocation might require revision., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Adenoviruses are double-stranded DNA viruses that typically cause mild self-limiting respiratory, ocular, and gastrointestinal infections. In immunocompromised patients, especially transplant recipients, the infection can be severe, with dissemination and multiorgan failure. In intestinal transplant recipients, the incidence is as high as 57%. To our knowledge, no standardized guidelines or U.S. Food and Drug Administration-approved medications exist for the treatment of adenovirus disease., Aims: We describe two isolated intestinal transplant recipients who developed adenovirus disease (viremia with viral enteritis) that was managed with a new experimental drug, brincidofovir (an oral lipid conjugate prodrug of cidofovir), as salvage therapy., Results: The first patient was a 44-year-old woman who developed adenoviral enteritis 1 month after transplantation, which resolved with ribavirin therapy. Two weeks later, the infection recurred, and brincidofovir was initiated. While receiving this therapy for 3 months, she developed severe acute rejection, which was managed with rabbit antithymocyte globulin followed by infliximab. Eventually, complete resolution of the rejection and adenoviral enteritis was achieved. At 12 months posttransplantation, the patient was healthy and tolerating enteral feeding. The second patient was a 28-year-old man who had undergone isolated intestinal transplantation 6 years before he presented with generalized weakness and an increased ostomy output; he was diagnosed with adenoviral enteritis. Maintenance immunosuppression was reduced, and brincidofovir was started. The infection resolved with a month of therapy. Six months after the infection, he was healthy and tolerating enteral feeding., Conclusion: This is the first publication, to our knowledge, to describe two cases in which brincidofovir was used to successfully treat adenovirus infection in intestinal transplant recipients. Thus, these cases demonstrate that brincidofovir appears to be a safe and effective option in the management of adenoviral enteritis in these patients., (© 2018 Pharmacotherapy Publications, Inc.)

Nonalcoholic fatty liver disease is becoming the leading cause of disease resulting in liver transplantation (LT). As a result of this trend, more LT candidates are presenting with prior history of bariatric surgery (BS). Over the last decade, 960 patients underwent LT at our institution; 11 (1.1%) had prior BS. The most common type of BS was Roux-en-Y gastric bypass (n = 9) with 1 sleeve gastrectomy and 1 jejunoileal bypass. A total of 9 patients underwent LT alone, and 2 underwent simultaneous liver-kidney transplantation. The most common indication for LT was nonalcoholic steatohepatitis (n = 10) with 5 having additional diagnosis of alcoholic liver disease. The 30-day reoperation rate was 36.4% (n = 4); indications were bile duct repair (n = 3) and wound repair (n = 1). In the first 6 months after LT, biliary complications were seen in 54.5% (n = 6) of the patients. Both patient and graft survival rates at 1 and 2 years were 81.8% (n = 9) and 72.7% (n = 8), respectively. A total of 8 patients (72.7%) had indications for liver biopsy after LT; significant macrovesicular steatosis was found in 2 (18.2%). In patients with a history of alcohol consumption, 2 (40.0%) relapsed after LT. Two patients (18.2%) had a history of diet-controlled diabetes before LT; 1 of these patients became insulin dependent after LT. Mean body mass index (BMI) at LT was 31.0 ± 5.7 kg/m 2 . Mean BMI at 1, 6, and 12 months after LT was 28.3 ± 5.8, 28.0 ± 3.2, and 31.0 ± 6.6 kg/m 2 , respectively. Mean preoperative albumin was 2.6 ± 0.6 mg/dL. Patients showed improvement in albumin after LT, with mean albumin of 2.7 ± 0.6 and 3.2 ± 0.5 mg/dL at 1 and 3 months, respectively. The liver profile was stable after LT, with mean aspartate aminotransferase of 32.9 ± 18.4 and 26.6 ± 19.8 IU/L and alanine aminotransferase of 28.0 ± 17.5 and 30.2 ± 17.0 IU/L at 6 and 12 months, respectively. In conclusion, outcomes of LT patients with prior BS are comparable with other transplant recipients with regards to patient and graft survival and post-LT complication rates. Liver Transplantation 23 1415-1421 2017 AASLD., (© 2017 by the American Association for the Study of Liver Diseases.)

Biliary stricture is a common cause of morbidity after liver transplantation (LT). This study aimed to determine the risk factors for post-transplant biliary anastomotic strictures (BAS), focusing on perioperative platelet counts. We enrolled 771 consecutive recipients who underwent ABO-identical/compatible deceased donor LT with duct-to-duct biliary reconstruction from January 2000 to June 2012. BAS was identified in 142 cases. The median time for stricture development was 176 days. Preoperative and postoperative platelet counts within 5 days after LT were significantly lower in patients with BAS than those without BAS. Using cutoff values acquired by the receiver operating characteristic curve analysis, persistent postoperative thrombocytopenia was defined as platelet counts <41 × 1000/μl and <53 × 1000/μl on postoperative day (POD) 3 and POD 5, respectively. Multivariate analysis indicated persistent postoperative thrombocytopenia (OR = 2.38) was the only independent risk factor for BAS. No significant associations were observed in terms of donor and surgical factors. Multivariate analysis demonstrated estimated blood loss (OR = 1.01, per 100 ml) was an independent contributing factor for persistent postoperative thrombocytopenia. We demonstrated low platelet count was associated with progression of post-transplant BAS. Minimizing intraoperative blood loss potentially contributes to maintain post-transplant platelet count, which may reduce incidence of BAS., (© 2017 Steunstichting ESOT.)

Background: The positive impact of platelets has been recently implicated in liver transplantation (LT). The aim of this study was to determine the risk factors for graft loss and mortality after LT, focusing on perioperative platelet counts., Methods: We reviewed all deceased donor LT from 2000 to 2012 and enrolled 975 consecutive recipients. The risk factors for graft loss and mortality were analyzed by multivariate analysis, using Cox's regression model., Results: Using cutoff values acquired by receiver operating characteristics curve analysis, multivariate analyses determined that viral hepatitis C (hazard ratio [HR]=1.32), donor age >40 (HR=1.33), higher peak serum alanine aminotransferase (HR=1.01), reoperation within 30 days (HR=1.51), and platelet count <72 500/μL on postoperative day (POD) 5 (HR=1.30) were independent risk factors for graft loss. Viral hepatitis C (HR=1.33), reoperation within 30 days (HR=1.35), and platelet count <72 500/μL on POD 5 (HR=1.38) were independent risk factors for mortality., Conclusion: A low platelet count on POD 5 was associated with graft loss and mortality after LT. Platelet count <72 500/μL on POD 5 can be a predictor of poor graft and overall survival. Maintaining higher postoperative platelet counts could potentially improve graft and overall survival rates., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Portal vein thrombosis is common in patients with end-stage liver disease, with an incidence as high as 26% in liver transplant candidates. It is known to be associated with a high risk of morbidity and mortality posttransplantation, and its management can be challenging. The management options range from a simple thrombendvenectomy to multivisceral transplantation in cases with diffuse portomesenteric thrombosis. We report a case of liver transplantation in which we performed a rare reconstruction of the portal vein. Briefly, the patient had diffuse portomesenteric thrombosis, calcified aneurysmosis, and a large collateral coronary vein, to which we directly anastomosed the donor portal vein in an end-to-side fashion. This report describes a unique surgical approach for similar cases of severe portal vein thrombosis in liver transplant candidates., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to evaluate the outcome of patients with intrahepatic cholangiocarcinoma (ICCA) incidentally found in the explanted liver after liver transplantation., Material and Methods: We retrospectively reviewed 1188 recipients undergoing liver transplantation from August 2003 to August 2014; 13 patients were found to have ICCA (1.1%). Recurrence-free survival (RFS) rate was compared between ICCA patients and the matched cohort of 39 patients with hepatocellular carcinoma (HCC). We also investigate the relevance of clinical and pathological parameters in recurrence of ICCA., Results: ICCA patients showed significantly higher recurrence rate with lower 1-year and 3-year RFS rates than HCC patients (recurrence rate, 12.8% vs. 54.8%; 1-year and 3-year RFS rates, 94% and 84% vs. 67% and 42%). Of the 13 ICCA patients, 4 were diagnosed with a well-differentiated ICCA and 9 with a moderately-differentiated ICCA. There was no recurrence among those with a well-differentiated ICCA, whereas 78% recurred in the moderately-differentiated group. The median RFS time for the moderately-differentiated group was 13.0 months, yielding RFS rates of 56% at 1 year and 22% at 3 years., Conclusions: Liver transplantation in patients with a well-differentiated ICCA yielded excellent outcomes as compared to patients with a moderately-differentiated ICCA. This may allow consideration of transplantation in the setting of a well-differentiated ICCA, and obviate the need for adjuvant systemic treatment. Conversely, a moderately-differentiated ICCA carries a poor prognosis with a prohibitively high recurrence rate and poor survival. Liver transplantation should remain a contraindication in this group.

Unlabelled: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are surgical complications estimated to occur in 5% to 10% of patients. There are limited data regarding DVT/PE in the early postoperative period in liver transplant patients. The aim of this study is to determine risk factors that influence the incidence of DVT/PE and the effectiveness of prophylaxis., Methods: We reviewed the records of 999 patients who underwent initial liver transplant between January 2000 and June 2012 at Henry Ford Hospital. In 2011, a standardized prophylactic regimen using subcutaneous (SQ) heparin was initiated. All patients that developed either upper/lower extremity DVT or PE within the first 30 days of transplant formed the cohort of this study., Results: On multivariate analysis, only peripherally inserted central catheter (PICC) placement and SQ heparin were associated with DVT/PE. In patients receiving heparin, 3 (1.0%) had DVT/PE versus 25 (3.5%) who did not receive heparin (P = 0.03). Sixteen (6.9%) patients that had a PICC developed DVT/PE compared with 12 (1.6%) patients without a PICC (P < 0.001). In the heparin group, DVT/PE with PICC was reduced to 3 (3.0%) versus 13 (9.9%) in those with a PICC and did not receive heparin (P = 0.03). Mean time from transplant to DVT/PE diagnosis was 12.3 days. Length of hospitalization was significantly longer in patients who developed DVT/PE (18.5 vs 10.0 days, P < 0.001)., Conclusions: In this study, we demonstrated that PICC placement significantly increases the likelihood of DVT/PE in liver transplant recipients. Prophylactic SQ heparin effectively reduced DVT/PE events in this patient population.

Context-Burnout is a response to chronic strain within the workplace and is common across nursing professions. Little has been published about burnout in organ transplant nurses. Objective-To report the prevalence of the 3 main components of burnout (emotional exhaustion, depersonalization, and reduced personal accomplishment) in organ transplant nurses and to examine factors that contribute to the development of burnout in transplant nurses. Design-Cross-sectional survey of transplant nurses (recruited via listservs) on professional and personal demographics, decisional authority, psychological job demands, supervisor and coworker support, frequency and comfort with difficult patient interactions, and burnout. Participants-369 transplant nurses. Results-About half reported high levels of emotional exhaustion, 15.7% reported high levels of depersonalization, and 51.8% reported low levels of personal accomplishment. Working more hours per week, lower decisional authority, greater psychological job demands, lower perceived supervisor support, and greater frequency and discomfort with difficult patient interactions were significant predictors of emotional exhaustion. Greater frequency and discomfort with difficult patient interactions were significant predictors of depersonalization. Younger age, lower decisional authority, and greater discomfort with difficult patient interactions were predictors of low personal accomplishment. Conclusions-The study provides strong evidence of the presence of burnout in transplant nurses and opportunities for focused and potentially very effective interventions aimed at reducing burnout.

Donor genotype for polymorphisms near IFNL3 influences hepatitis C virus (HCV) therapy responsiveness. This relationship has not been studied in a sample of HCV-infected living donor liver transplantation (LDLT) recipients in the United States (US). We investigated the association of donor and recipient genotypes near the IFNL3 gene at a large US liver transplant center. Recipient homozygosity for rs12979860 C was associated with increased sustained virologic response (SVR) in antiviral treatment-experienced patients pretransplant (P = 0.055). Consistently, donor homozygosity for rs12979860 C was also associated with increased SVR in patients who received post-transplant antiviral therapy (P = 0.048). Transplantation of an rs12979860 CC graft confers a favorable post-transplant antiviral response among HCV-positive recipients in an LDLT setting. Recipients with the favorable rs12979860 genotype receiving antiviral therapy before transplant are also more likely to achieve SVR. The effect of genotype status in the era of direct-acting antiviral agents will require future study.

Unlabelled: Although experimental evidence has indicated that ischemia-reperfusion (I/R) injury of the liver stimulates growth of micrometastases and adhesion of tumor cells, the clinical impact of I/R injury on recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has not been fully investigated. To study this issue, we conducted a retrospective review of the medical records of 391 patients from two transplant centers who underwent LT for HCC. Ischemia times along with other tumor/recipient variables were analyzed as risk factors for recurrence of HCC. Subgroup analysis focused on patients with HCC who had pathologically proven vascular invasion (VI) because of the associated increased risk of micrometastasis. Recurrence occurred in 60 patients (15.3%) with median time to recurrence of 0.9 years (range, 40 days-4.6 years). Cumulative recurrence curves according to cold ischemia time (CIT) at 2-hour intervals and warm ischemia time (WIT) at 10-minute intervals showed that CIT>10 hours and WIT>50 minutes were associated with significantly increased recurrence (P=0.015 and 0.036, respectively). Multivariate Cox's regression analysis identified prolonged cold (>10 hours; P=0.03; hazard ratio [HR]=1.9) and warm (>50 minutes; P=0.003; HR=2.84) ischemia times as independent risk factors for HCC recurrence, along with tumor factors, including poor differentiation, micro- and macrovacular invasion, exceeding Milan criteria, and alpha-fetoprotein>200 ng/mL. Prolonged CIT (P=0.04; HR=2.24) and WIT (P=0.001; HR=5.1) were also significantly associated with early (within 1 year) recurrence. In the subgroup analysis, prolonged CIT (P=0.01; HR=2.6) and WIT (P=0.01; HR=3.23) were independent risk factors for recurrence in patients with VI, whereas there was no association between ischemia times and HCC recurrence in patients with no VI., Conclusion: Reducing ischemia time may be a useful strategy to decrease HCC recurrence after LT, especially in those with other risk factors., (© 2014 by the American Association for the Study of Liver Diseases.)

Background: Absolute lymphocyte count (ALC) is considered a surrogate marker for the level of immunosuppression and nutritional status of patients and a prognostic factor for survival and recurrence in several cancers. The aim of this study was to investigate the prognostic value of peritransplant ALC for the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT)., Methods: HCC patients who underwent LT between 2000 and 2010 were evaluated. Exclusion criteria were combined HCC and cholangiocarcinoma. Peritransplant ALCs (before LT and 2 weeks and 1 month after LT) were analyzed along with tumor, operative, and donor characteristics to identify risk factors for the recurrence of HCC., Results: HCC developed in 27 of the 173 LT patients investigated for risk factors (15.6%). The median time to recurrence was 1.14 years. Low ALCs before and after LT were associated with a higher recurrence rate in a continuous manner (before LT: hazard ratio=1.12, P=0.003; 2 weeks after LT: hazard ratio=1.14, P=0.008; 1 month after LT: hazard ratio=1.06, P=0.055) (increased risk per 100/μL down). On multivariate Cox regression analysis, peritransplant persistent lymphopenia (<1000/μL before LT and <500/μL at 2 weeks and 1 month after LT) was an independent risk factor for cancer recurrence (hazard ratio=7.05, P<0.001), along with tumor characteristics., Conclusion: Peritransplant lymphopenia is a powerful prognostic factor for the recurrence of HCC after LT, which suggests that maintaining ALCs in LT patients might improve cancer outcome.

Unlabelled: Lymphocytes play an active role in natural immunity against hepatitis C virus (HCV). We hypothesized that a lower absolute lymphocyte count (ALC) may alter HCV outcome after liver transplantation (LT). The aim of this study was to investigate the impact of peritransplant ALC on HCV recurrence following LT. A total of 289 LT patients between 2005 and 2011 were evaluated. Peritransplant ALC (pre-LT, 2-week, and 1-month post-LT) and immunosuppression were analyzed along with recipient and donor factors in order to determine risk factors for HCV recurrence based on METAVIR fibrosis score. When stratifying patients according to pre- and post-LT ALC (<500/μL versus 500-1,000/μL versus >1,000/μL), lymphopenia was significantly associated with higher rates of HCV recurrence with fibrosis (F2-4). Multivariate Cox regression analysis showed posttransplant ALC at 1 month remained an independent predictive factor for recurrence (P = 0.02, hazard ratio [HR] = 2.47 for <500/μL). When peritransplant ALC was persistently low (<500/μL pre-LT, 2-week, and 1-month post-LT), patients were at significant risk of developing early advanced fibrosis secondary to HCV recurrence (F3-4 within 2 years) (P = 0.02, HR = 3.16). Furthermore, severe pretransplant lymphopenia (<500/μL) was an independent prognostic factor for overall survival (P = 0.01, HR = 3.01). The use of rabbit anti-thymocyte globulin induction (RATG) had a remarkable protective effect on HCV recurrence (P = 0.02, HR = 0.6) despite its potential to induce lymphopenia. Subgroup analysis indicated that negative effects of posttransplant lymphopenia at 1 month (<1,000/μL) were significant regardless of RATG use and the protective effects of RATG were independent of posttransplant lymphopenia., Conclusion: Peritransplant ALC is a novel and useful surrogate marker for prediction of HCV recurrence and patient survival. Immunosuppression protocols and peritransplant management should be scrutinized depending on peritransplant ALC., (© 2013 by the American Association for the Study of Liver Diseases.)

In patients infected with chronic hepatitis B virus (HBV) that goes untreated, therapeutic options are limited once the disease decompensates, and orthotopic liver transplantation is often the only treatment available to save the patient's life. After liver transplantation, combined therapy with hepatitis B immune globulin (HBIG) and a nucleos(t)ide analog is the standard of practice for the prevention of HBV recurrence. Historically, nucleos(t)ide analogs such as lamivudine and adefovir have been used with low-dose HBIG for the prevention of HBV recurrence after liver transplantation. However, these analogs are ineffective when used alone due the emergence of resistance mutations. Newer nucleos(t)ide analogs such as tenofovir disoproxil fumarate have demonstrated higher resistance thresholds and effective viral suppression when paired with low-dose HBIG. In this case series, we evaluated the safety and efficacy of switching four patients from low-dose HBIG plus nucleos(t)ide analog therapy for the prevention of HBV recurrence to a combination tenofovir-emtricitabine regimen. At the end of follow-up, all patients remained hepatitis B surface antigen negative and had HBV DNA levels of less than 10 IU/ml. Additionally, no tenofovir-associated nephrotoxicity was observed among the four patients. Tenofovir-emtricitabine monotherapy in lieu of HBIG plus nucleos(t)ide analog therapy demonstrated prevention of HBV recurrence without tenofovir-associated nephrotoxicity after 9 months of follow-up in all four patients and up to 15 months in one patient., (© 2013 Pharmacotherapy Publications, Inc.)

Minimally invasive procedures are considered to be safe and effective approaches to the management of surgical liver disease. However, this indication remains controversial for living donor hepatectomy. Between 2000 and 2011, living donor right hepatectomy (LDRH) was performed 58 times. Standard right hepatectomy was performed in 30 patients via a subcostal incision with a midline extension. Minimally invasive procedures began to be used for LDRH in 2008. A hybrid technique (hand-assisted laparoscopic liver mobilization and minilaparotomy for parenchymal dissection) was developed and used in 19 patients. In 2010, an upper midline incision (10 cm) without laparoscopic assistance for LDRH was innovated, and this technique was used in 9 patients. The perioperative factors were compared, and the indications for minimally invasive LDRH were investigated. The operative blood loss was significantly less for the patients undergoing a minimally invasive procedure versus the patients undergoing the standard procedure (212 versus 316 mL, P = 0.001), and the operative times were comparable. The length of the hospital stay was significantly shorter for the minimally invasive technique group (5.9 versus 7.8 days, P < 0.001). The complication rates were 23% and 25% for the standard technique and minimally invasive technique groups, respectively (P = 0.88). Patients undergoing minilaparotomy LDRH had a body mass index (24.0 kg/m(2)) similar to that of the hybrid technique patients (25.8 kg/m(2), P = 0.36), but the graft size was smaller (780 versus 948 mL, P = 0.22). In conclusion, minimally invasive LDRH can be performed without safety being impaired. LDRH with a 10-cm upper midline incision and without laparoscopic assistance may be appropriate for donors with a smaller body mass. Laparoscopic assistance can be added as needed for larger donors. This type of LDRH with a 10-cm incision is innovative and is recommended for experienced centers., (Copyright © 2012 American Association for the Study of Liver Diseases.)

Background: Non-alcoholic steatohepatitis (NASH) and cryptogenic cirrhosis (CC) are increasing indications for orthotopic liver transplantation (OLT). The aim of this study is to describe our outcomes and delineate predictors of recurrence of NASH and CC after OLT., Methods: This is a retrospective study from 1996 to 2008. Donor and recipient demographics, metabolic profile, insulin and steroid intake, immunosuppression regimen, operative factors, outcomes, and pathologies were reviewed. Fisher's exact test, Cox regression models, and Kaplan-Meier plots were used., Results: A total of 83 patients were included. Recurrence occurred in 20 patients. Thirty-four percent of the patients with metabolic syndrome (MS) had recurrence of NASH or CC compared with 13% of the patients without MS (p = 0.05). Recurrence also occurred in 32% of the patients with hypertension (HTN) vs. 12% in those without HTN (p = 0.05). Thirty-seven percent of those on insulin had recurrence vs. 6% of those not on insulin (p = 0.05). Five-yr survival probability for patients with MS, HTN, and insulin use was 52%, 61%, and 58%, respectively., Conclusions: Higher recurrence of NASH and CC was associated with presence of MS, HTN and insulin use. Recurrence should be further evaluated in larger studies, with special emphasis on management of MS and prevention strategies., (© 2012 John Wiley & Sons A/S.)

Introduction: This case report demonstrates that the differential immunohistochemical reactivities of Siemens' Double Antibody Glucagon compared to DakoCytomation's Polyclonal Rabbit Anti-Human Glucagon allow for pathologic distinction of enteral versus pancreatic glucagonoma., Case Presentation: A 64-year-old Caucasian man was diagnosed with a duodenal enteroglucagonoma following presentation with obstructive jaundice. He had a low serum glucagon level using Siemens' Double Antibody Glucagon, a clinical syndrome consistent with glucagon hypersecretion. A periampullary mass biopsy proved to be a neuroendocrine tumor, with positive immunohistochemical reactivity to DakoCytomation's Polyclonal Rabbit Anti-Human Glucagon., Conclusions: Differential comparison of the immunohistochemical reactivities of Siemens' Double Antibody Glucagon and DakoCytomation's Polyclonal Rabbit Anti-Human Glucagon discerns enteroglucagon from pancreatic glucagon.

Introduction: Hepatic artery thrombosis following orthotopic liver transplant is one of the most common reasons for early graft failure. Meticulous reconstitution of hepatic artery flow remains essential for good outcomes. Prior surgery, body habitus, hepatic artery inadequacy and anatomic differences can complicate hepatic artery revascularization., Case Presentation: We report a single institution's experience, from January 1996 to January 2007, using splenic artery inflow in seven patients with inadequate native hepatic arteries., Conclusion: End-to-side anastomosis was associated with postanastomotic intimal hyperplasia. End-to-end anastomosis provided effective hepatic inflow, demonstrated splenic and pancreatic safety, and was not associated with the intimal hyperplasia experienced with end-to-side anastomosis.