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Despite refinements in surgical techniques for liver transplantation, liver size disparity remains one of the most common problems in patients. The general aim of this study is to estimate the size of liver volume and length of the liver in the midclavicular section and also estimate body parameters such as BMI, BSA, and BSI. The height and weight of patients going for abdominal CT were measured. The BSA, BSI and BMI were then calculated and compared to other measurements. Using MeVisLab software each patient liver volume was measured from their CT images.

Cirrhosis is characterized as the progress of regenerative nodules surrounded by fibrous bands in response to chronic hepatic injury and causes portal hypertension and end stage hepatic disease. Following liver injury, liver progenitor cells (LPCs) can be activated and differentiate into hepatocytes in order to awaken liver regeneration and reach homeostasis. Recent research has uncovered some new sources of LPCs. Here, we update the mechanisms of LPCs-mediated liver regeneration in cirrhosis by introducing the origin of LPCs and LPCs' niche with a discussion of the influence of LPC-related cells. This article analyzes the mechanism of regeneration and activation of LPCs in cirrhosis in recent years aiming to provide help for clinical application. Copyright (C) 2020, Chongqing Medical University. Production and hosting by Elsevier B.V.

Cirrhosis is characterized as the progress of regenerative nodules surrounded by fibrous bands in response to chronic hepatic injury and causes portal hypertension and end stage hepatic disease. Following liver injury, liver progenitor cells (LPCs) can be activated and differentiate into hepatocytes in order to awaken liver regeneration and reach homeostasis. Recent research has uncovered some new sources of LPCs. Here, we update the mechanisms of LPCs-mediated liver regeneration in cirrhosis by introducing the origin of LPCs and LPCs' niche with a discussion of the influence of LPC-related cells. This article analyzes the mechanism of regeneration and activation of LPCs in cirrhosis in recent years aiming to provide help for clinical application. Copyright (C) 2020, Chongqing Medical University. Production and hosting by Elsevier B.V.

Summary High‐risk combinations of recipient and graft characteristics are poorly defined for liver retransplantation (reLT) in the current era. We aimed to develop a risk model for survival after reLT using data from the European Liver Transplantation Registry, followed by internal and external validation. From 2006 to 2016, 85 067 liver transplants were recorded, including 5581 reLTs (6.6%). The final model included seven predictors of graft survival: recipient age, model for end‐stage liver disease score, indication for reLT, recipient hospitalization, time between primary liver transplantation and reLT, donor age, and cold ischemia time. By assigning points to each variable in proportion to their hazard ratio, a simplified risk score was created ranging 0–10. Low‐risk (0–3), medium‐risk (4–5), and high‐risk (6–10) groups were identified with significantly different 5‐year survival rates ranging 56.9% (95% CI 52.8–60.7%), 46.3% (95% CI 41.1–51.4%), and 32.1% (95% CI 23.5–41.0%), respectively (P, The retransplantation risk score.

There is enough clinical evidence that a T-tube use in biliary reconstruction at adult liver transplantation (LT) does not significantly modify the risk of biliary stricture/leak, and it may even sustain infective and metabolic complications. Thus, the policy on T-tube use has been globally changing, with progressive application of more restrictive selection criteria. However, there are no currently standardized indications in such change, and many LT Centers rely only on own experience and routine. A nation-wide survey was conducted among all the 20 Italian adult LT Centers to investigate the current policy on T-tube use. It was found that 20% of Centers completely discontinued the T-tube use, while 25% Centers used it routinely in all LT cases. The remaining 55% of Centers applied a selective policy, based on criteria of technical complexity of biliary reconstruction (72.7%), followed by low-quality graft (63.6%) and high-risk recipient (36.4%). A T-tube use > 50% of annual caseload was not associated with high-volume Center status (> 70 LT per year), an active pediatric or living-donor transplant program, or use of DCD grafts. Only 10/20 (50%) Centers identified T-tube as a potential risk factor for complications other than biliary stricture/leak. In these cases, the suspected pathogenic mechanism comprised bacterial colonization (70%), malabsorption (70%), interruption of the entero-hepatic bile-acid cycle (50%), biliary inflammation due to an indwelling catheter (40%) and gut microbiota changes (40%). In conclusion, the prevalence of T-tube use among the Italian LT Centers is still relatively high, compared to the European trend (33%), and the potential detrimental effect of T-tube, beyond biliary stricture/leak, seems to be somehow underestimated.

Objectives Thrombocytopenia is a common problem among liver transplant recipients. However, various patterns of change in platelet counts during adult liver transplant have been reported in the literature. This study aimed to evaluate alterations in platelet count according to the surgical phase (preanhepatic, anhepatic, after reperfusion) and during the early postoperative period of liver transplant. Materials and methods Perioperative data from 100 patients undergoing deceased donor liver transplant were reviewed, including platelet count-related data. Platelet counts were measured at predefined time points throughout the procedure: immediately before induction of anesthesia, at the early neo-hepatic stage (10 min after graft reperfusion), immediately after admission to the intensive care unit posttransplant, and 6 hours posttransplant. Platelet counts were then measured daily during stay in the intensive care unit. Results Mean baseline platelet count before transplant and anesthesia was 97.92 × 109/L. A peak platelet count was seen in the early neo-hepatic stage. Platelet counts then decreased sharply in the first 6 hours after transplant. A slight decrease in platelet counts continued until the third day after the surgery; finally, on day 6 posttransplant, platelet counts increased significantly. Conclusions Our study showed a significant sudden increase in platelet counts during the early neo-hepatic phase in many liver transplant recipients. Therefore, our results suggest that it is reasonable to avoid platelet transfusion for most liver transplant recipients during transplant surgery.

O sistema MELD está sedimentado no Brasil. O aumento do MELD para alocação, a influência de diferentes etiologias e o desequilíbrio na lista, secundários à concessão de situções especiais têm suscitado discussões para modernização do sistema. No Brasil, cada estado é responsável pela organização da captação de órgãos, resultando dm um sistema heterogêneo. Objetivo: Análise do tempo de espera e MELD necessário para transplante, o impacto das diferentes etiologias e concessão de situações especiais no âmbito do estado do Paraná. Método: Análise de 1248 transplantes de fígado adulto entre 2010 e 2018, estratificados conforme a etiologia, MELD e tempo de espera. Resultados: Idade de 52+11,4 anos. Tempo de espera em lista de 112+197 dias. 83,78% dos casos transplantaram em período inferior a seis meses. Situações especiais foram concedidas em 8,25% (n=103) dos casos; não houve Diferença significativa no tempo de espera em lista no grupo com (110+107) e sem (112+197) situação especial. MELD do transplante (19,69+7,86), MELD corrigido (22,24+6,42). Apesar de diferente entre grupos de etiologia, o MELD não apresentou padrão de crescimento com o passar do tempo. A etiologia álcool (27,08%) e infecções virais (23,56%) foram as mais frequentes. 29,75% dos transplantes foram realizados com MELD acima de 75%; não houve modificação das etiologias mais comuns nesse subgrupo. A oferta de órgãos cresceu de 8,9 pmp (2010) para 47,7 pmp (2017). Conclusão: O impacto do progressivo aumento do MELD e tempo de espera em lista, secundários à concessão de situações especiais não são observados na lista de espera no estado do Paraná. Essa discrepância provavelmente é secundária ao contínuo crescimento, de maneira quase paralela ao número de doadores e transplantes realizados.

Survival rates for patients following liver transplantation exceed 90% at 12 months and approach 70% at 10 years. Part 1 of this guideline has dealt with all aspects of liver transplantation up to the point of placement on the waiting list. Part 2 explains the organ allocation process, organ donation and organ type and how this influences the choice of recipient. After organ allocation, the transplant surgery and the critical early post-operative period are, of necessity, confined to the liver transplant unit. However, patients will eventually return to their referring secondary care centre with a requirement for ongoing supervision. Part 2 of this guideline concerns three key areas of post liver transplantation care for the non-transplant specialist: (1) overseeing immunosuppression, including interactions and adherence; (2) the transplanted organ and how to initiate investigation of organ dysfunction; and (3) careful oversight of other organ systems, including optimising renal function, cardiovascular health and the psychosocial impact. The crucial significance of this holistic approach becomes more obvious as time passes from the transplant, when patients should expect the responsibility for managing the increasing number of non-liver consequences to lie with primary and secondary care.

Adult hepatic progenitor cells (HPCs)/oval cells are bipotential progenitors that participate in liver repair responses upon chronic injury. Recent findings highlight HPCs plasticity and importance of the HPCs niche signals to determine their fate during the regenerative process, favoring either fibrogenesis or damage resolution. Transforming growth factor-β (TGF-β) and hepatocyte growth factor (HGF) are among the key signals involved in liver regeneration and as component of HPCs niche regulates HPCs biology. Here, we characterize the TGF-β-triggered epithelial–mesenchymal transition (EMT) response in oval cells, its effects on cell fate in vivo, and the regulatory effect of the HGF/c-Met signaling. Our data show that chronic treatment with TGF-β triggers a partial EMT in oval cells based on coexpression of epithelial and mesenchymal markers. The phenotypic and functional profiling indicates that TGF-β-induced EMT is not associated with stemness but rather represents a step forward along hepatic lineage. This phenotypic transition confers advantageous traits to HPCs including survival, migratory/invasive and metabolic benefit, overall enhancing the regenerative potential of oval cells upon transplantation into a carbon tetrachloride-damaged liver. We further uncover a key contribution of the HGF/c-Met pathway to modulate the TGF-β-mediated EMT response. It allows oval cells expansion after EMT by controlling oxidative stress and apoptosis, likely via Twist regulation, and it counterbalances EMT by maintaining epithelial properties. Our work provides evidence that a coordinated and balanced action of TGF-β and HGF are critical for achievement of the optimal regenerative potential of HPCs, opening new therapeutic perspectives. Stem Cells 2019;37:1108–1118

Aims Tacrolimus is a narrow therapeutic range drug that requires fine dose adjustment, for which pharmacokinetic (PK) models have been amply proposed in renal, but not in liver, transplant recipients. This study aimed to build population PK models and Bayesian estimators (BEs) in adult de novo liver transplant patients receiving either the immediate-release (Prograf, twice daily, TD) or prolonged-release (Advagraf, once daily, OD) forms to help PK-guided dose individualization. Methods In total, 160 tacrolimus concentration-time profiles (1654 samples) were collected from 80 patients, at day 7 (D7) and week 6 (W6) post-transplant. Four population PK models were developed using in-parallel parametric and nonparametric approaches for each formulation and period post-transplant. The best limited sampling strategies for estimating the area-under-the-curve (AUC) were selected by comparing predicted values to an independent dataset. Finally, the doses required to reach AUC targets were estimated using each BE and compared to the doses obtained using the trapezoidal AUC. Results Tacrolimus PK was best described using a 1-compartmental model with first-order elimination and 2 γ-distributions to describe the absorption. In the validation datasets, Bayesian AUC estimates yielded mean bias/root mean squared prediction error of −5.06%/13.43% (OD D7), 2.25%/8.51% (OD W6), −2.36%/7.27% (TD D7) and 0.87%/9.07% (TD W6) for the in-parallel parametric approach; and 8.95%/17.84% (OD D7), −0.11%/10.13% (OD W6), 3.57%/18.40% (TD D7) and 4.48%/12.59% (TD W6) for the nonparametric approach. Conclusion The BEs and limited sampling strategies proposed here are able to predict accurately and precisely tacrolimus AUC in liver patients using only 3 plasma concentrations. The dosing methods are available on our ImmunoSuppressive Bayesian dose Adjustment website (www.pharmaco.chu-limoges.fr).

Background Routine use of (MBR) by Roux en Y in adult Orthotopic Liver Transplantation (OLT) has not been elucidated. The usual choice of enteric drainage got expected morbidities of biliary enteric anastomosis. Patients of liver transplant clinical differences are compared. Choices, current status, efficacy, application, short and long term outcome of biliary reconstruction by (MBR) roux en Y anastomosis in adult liver transplant was compared to Conventional roux en y. Aim The primary aim of the study is to clarify the influence to the diseased liver recipient duct to the future graft biliary drainage. Methods Study of consecutive liver transplant patients was retrieved. Total Number of 1234 OLT, By the End of July 2014. Group A 16 patients of Conventional Period up to 22 March, 2006. Group B 50 patients of (MBR) up to 31 JULY 2014. Results In group A 8/16 got short and long term complication. However, in group B only 4/50 got short term problems, with no death. Conclusion In Spite of the drawback of adult OLT roux en Y hepatico-jejunal anastomosis including anatomical challenges and graft position, we developed graft survival in adults liver transplant with widened application of (MBR). There is accessible and durable intact biliary drainage choice by (MBR) hepatica enteric anastomosis for adults OLT patients that can be encouraged and advised by microscopic surgery.

Hepatic, pancreatic, and biliary (HPB) organoids are powerful tools for studying development, disease, and regeneration. As organoid research expands, the need for clear definitions and nomenclature describing these systems also grows. To facilitate scientific communication and consistent interpretation, we revisit the concept of an organoid and introduce an intuitive classification system and nomenclature for describing these 3D structures through the consensus of experts in the field. To promote the standardization and validation of HPB organoids, we propose guidelines for establishing, characterizing, and benchmarking future systems. Finally, we address some of the major challenges to the clinical application of organoids.

Somatic cell reprogramming and tissue repair share relevant factors and molecular programs. Here, Dickkopf-3 (DKK3) is identified as novel factor for organ regeneration using combined transcription-factor-induced reprogramming and RNA-interference techniques. Loss of Dkk3 enhances the generation of induced pluripotent stem cells but does not affect de novo derivation of embryonic stem cells, three-germ-layer differentiation or colony formation capacity of liver and pancreatic organoids. However, DKK3 expression levels in wildtype animals and serum levels in human patients are elevated upon injury. Accordingly, Dkk3-null mice display less liver damage upon acute and chronic failure mediated by increased proliferation in hepatocytes and LGR5+ liver progenitor cell population, respectively. Similarly, recovery from experimental pancreatitis is accelerated. Regeneration onset occurs in the acinar compartment accompanied by virtually abolished canonical-Wnt-signaling in Dkk3-null animals. This results in reduced expression of the Hedgehog repressor Gli3 and increased Hedgehog-signaling activity upon Dkk3 loss. Collectively, these data reveal Dkk3 as a key regulator of organ regeneration via a direct, previously unacknowledged link between DKK3, canonical-Wnt-, and Hedgehog-signaling., publishedVersion

Highlights • The global pandemic of Coronavirus Disease 2019 has drastically affected liver transplantation programs worldwide. • There was a significant decrease in the number of organ donations and liver transplantations performed in France. • The North East area which was the main Coronavirus Disease 2019 cluster area had > 25% decrease of the multiorgan procurement and liver transplantations in 2020 compared to 2019., Background The global pandemic of Coronavirus Disease 2019 (COVID-19) has potentially affected liver transplantation (LT) programs worldwide. The aim of this study was to determine whether the COVID-19 outbreak affected organ donation and LT activity in France. Methods Data on the number of brain-dead donor procurements and adult liver transplantations were compared between two periods (1st January- 31st May 2019 vs. 1st January-31st May 2020). Main findings There was a 28% decrease in the number of organ donations in 2020 (543 in 2020vs. 752 organ donations in 2019). A 22% decrease in the number of liver transplantations was also observed: 435 in 2020 vs. 556 LTs in 2019. Overall, the North East area which was the main COVID-19 cluster area, had > 25% decrease of the multiorgan procurement (-33% compared to 2019), and liver transplantation (-26% compared to 2019) activities in 2020 Conclusion This analysis confirmed that during the COVID-19 outbreak there was a significant decrease in the number of organ donations and liver transplantations performed in France.

Objective To identify factors that accurately predict 1-year survival for liver transplant recipients with a MELD score ≥40. Background Although transplant is beneficial for patients with the highest acuity (MELD ≥40), mortality in this group is high. Predicting which patients are likely to survive for >1 year would be medically and economically helpful. Methods The Scientific Registry of Transplant Recipients database was reviewed to identify adult liver transplant recipients from 2002 through 2016 with MELD score ≥40 at transplant. The relationships between 44 recipient and donor factors and 1-year patient survival were examined using random survival forests methods. Variable importance measures were used to identify the factors with the strongest influence on survival, and partial dependence plots were used to determine the dependence of survival on the target variable while adjusting for all other variables. Results We identified 5309 liver transplants that met our criteria. The overall 1-year survival of high-acuity patients improved from 69% in 2001 to 87% in 2016. The strongest predictors of death within 1 year of transplant were patient on mechanical ventilator before transplantation, prior liver transplant, older recipient age, older donor age, donation after cardiac death, and longer cold ischemia. Conclusions Liver transplant outcomes continue to improve even for patients with high medical acuity. Applying ensemble learning methods to recipient and donor factors available before transplant can predict survival probabilities for future transplant cases. This information can be used to facilitate donor/recipient matching and to improve informed consent.

The survival of liver transplantation (LT) recipients has been improved remarkably in short-term. The major causes of mortality in long-term include nonimmunological causes such as cardiovascular, de novo malignancy, chronic kidney disease, and recurrence of primary disease. Rejection-related mortality is rare in the long-term after LT. We discuss nonrejection causes of long-term morbidity/mortality, risk factors, and management strategies in LT recipients. In addition, we discuss osteoporosis, contraception, and pregnancy in LT recipients.

Objective: To assess long term graft and patient survival after donor liver retransplantation in children in Australia and New Zealand during 1986–2017; to determine the factors that influence survival. Design: Retrospective cohort analysis (registry data). Setting, participants: Australia and New Zealand Liver Transplant Registry data for all liver retransplantations in children (under 18 years of age), 1986–2017, in all four paediatric and six adult liver transplantation centres in the two countries. Main outcome measures: Graft and patient survival at one, 5, 10 and 15 years. Results: 142 liver retransplantations were undertaken in children (59 during 1986–2000, 83 during 2001–2017). Kaplan–Meier survival analysis indicated that survival was significantly greater during 2001–2017 than 1986–2000 (P

AIM. Posttransplant diabetes mellitus (PTDM) is a metabolic complication that usually occurs after liver transplantation (LT) due to immunosuppression. In this study, our aim was to identify PTDM incidence after LT in our center and the potential risk factors. MATERIALS AND METHODS. In this study, 238 adult LT patients were evaluated in terms of PTDM development. RESULTS. Of 238 patients included in the study, 170 (71.4%) were male, 68 (28.6%) were female and the mean age was 43.5± 13.7 years. Of all patients, PTDM developed in 24 (10.1%). Transient-Hyperglycemia (t-HG) was detected in 31 (13%) patients. PTDM and t-HG patients had a greater body weight than non-PTDM patients (BMI kg/m(2): 27.6± 5.3, 25.8± 4.3and 23.9± 3.3, respectively p

The mammalian liver possesses a remarkable regenerative ability. Two modes of damage response have been described: (1) The “oval cell” response emanates from the biliary tree when all hepatocytes are affected by chronic liver disease. (2) A massive, proliferative response of mature hepatocytes occurs upon acute liver damage such as partial hepatectomy (PHx). While the oval cell response has been captured in vitro by growing organoids from cholangiocytes, the hepatocyte proliferative response has not been recapitulated in culture. Here, we describe the establishment of a long-term 3D organoid culture system for mouse and human primary hepatocytes. Organoids can be established from single hepatocytes and grown for multiple months, while retaining key morphological, functional and gene expression features. Transcriptional profiles of the organoids resemble those of proliferating hepatocytes after PHx. Human hepatocyte organoids proliferate extensively after engraftment into mice and thus recapitulate the proliferative damage-response of hepatocytes. Modeling the regenerative ability of the liver in response to acute damage using long-term 3D organoid cultures in mice and human cells yields proliferative hepatocytes that are able to successfully engraft in animal models.

In liver transplantation, both cold and warm ischemia times are known to impact early graft function. The extraction time is a period during the initial phase of organ cooling which occurs during deceased donor procurement. During this time, the organ is at risk of suboptimal cooling. Whether donor extraction time, the time from donor aortic cross-clamp to removal of the donor organ from the body cavity has an effect on early graft function is not known.We investigated the effect of donor extraction time on early graft function in 292 recipients of liver grafts procured locally and transplanted at our center between June 2012 and December 2016. Early graft function was assessed using the model of early allograft function score in a multivariable regression model including donor extraction time, cold ischemia time, warm ischemia time, donor risk index, and terminal donor sodium.Donor extraction time had an independent effect on early graft function measured by the model of early allograft function score (coefficient, 0.021; 95% confidence interval, 0.007-0.035; P0.01; for each minute increase of donor extraction time). Besides donor extraction time, cold ischemia time, warm ischemia time, and donor risk index had a significant effect on early graft function.We demonstrate an independent effect of donor extraction time on graft function after liver transplantation. Efforts to minimize donor extraction time could improve early graft function in liver transplantation.

Cytomegalovirus (CMV) is a common posttransplant infection, most commonly seen in settings of excessive immunosuppression. Before the advent of CMV specific antiviral therapies, the standard treatment approaches for CMV disease were immunosuppression reductions to let the transplant recipient mount an immunologic response against CMV. Additionally, CMV is rarely identified as causing stricturing enteritis and has not previously been reported as causing stricturing enteritis in an adult transplant recipient. All identified reports of stricturing CMV enteritis have been reported in either pediatric patient populations or those with severe immunosuppression from human immunodeficiency virus and acquired immune deficiency syndrome. Our report presents the unusual case of an adult liver transplant recipient many years after transplant and on minimal immunosuppression with mycophenolate alone who developed stricturing CMV enteritis.

Data on adult liver transplants performed in the US in 2016 are no-table for (1) the largest total number of transplants performed (7841); (2) the shortest median waiting time in recent history (11.3 months); (3) continued reduction in waitlist registrations and transplants for hepatitis C-related indications; (4) increasing numbers of patients whose clinical profiles are consistent with non-alcoholic fatty liver disease; and (5) equilibration of transplant rates in patients with and without hepatocellular carcinoma. Despite the increase in the number of available organs, waitlist mortality remained an important concern. Graft survival rates continued to improve. In 2016, 723 new active candidates were added to the pediatric liver transplant waiting list, down from a peak of 826 in 2005. The number of prevalent candidates (on the list on December 31 of the given year) was stable, 408 active and 169 inactive. The number of pediatric living donor liver transplants decreased from a peak of 79 in 2015 to 62 in 2016, with most from donors closely related to the recipients. Graft survival continued to improve over the past decade among recipients of deceased donor and living donor livers.

Objective: The primary aim of this study is to evaluate the role of split liver transplantation (SLT) in a combined pediatric and adult liver transplant center. The secondary aim is to reflect on our clinical practice and discuss strategies to build a successful split program using an “intention to split policy.” Background: SLT is an established procedure to expand the organ pool and reduce wait list mortality; however, technical and logistic issues are limiting factors. Methods: Prospectively collected data and outcomes of SLT procedures performed between November 1992 and March 2014 were analyzed retrospectively. To assess the effect of standardization and learning curve, the experience was divided into 2 time periods. Results: Out of 3449 liver transplant procedures performed, 516(15%) were SLT. The recipients included 266 children (290 grafts; 56%) and 212 adults (226 grafts; 44%). The median donor age was 25(7–63 years) and the median weight was 70(22–111 kg). The cold and warm ischemic times improved significantly during the second period (SP) (2001–2014). With experience, there was a significant reduction in the biliary complications for both grafts. The introduction of “intention to split policy” resulted in a significantly increased usage of SLT. There was no mortality on the pediatric wait list for last 4 years. Over the last decade 65% of our pediatric transplants were SLT. The overall 1-, 5-, 10-year patient and graft survival of left graft recipients was 91%, 90%, and 89% and 90%, 87%, and 86%. For right grafts it was 87%, 82%, and 81% and 82%, 81%, and 79%, respectively. Conclusions: SLT is an effective surgical strategy to meet the demands in a combined adult and pediatric transplant center. Good outcomes can be achieved with a standardized technique.

Critical care management after liver transplantation requires a sophisticated monitoring and multi-disciplinary team work. An experienced team and advanced critical care/hospital facilities are necessary for an ideal critical care treatment today. Critical care management after liver transplantation has shown a rapid development since the introduction of liver transplantation. While one-year survival rate after liver transplantation was 79% in 1998, it raised to 90% in 2008 related to the improvements in preoperative optimization, surgical technique, anesthetic management, organ preservation, critial care and immunosuppressive treatment. Treatment of severe coagulopathy, prompt hemodynamic and respiratory stabilization, early weaning from mechanical ventilation, proper fluid-electrolyte therapy, prevention of graft rejection, protection of renal functions and prophylaxis/treatment of infection are particularly important in critical care management after liver transplantation. As early postoperative period of liver transplantation is a critical phase; close monitoring, stabilization of cardiopulmonary functions, frequent evaluation of graft function, early diagnosis of complications and rapid treatment of extrahepatic organ failure are mandatory in order to reduce mortality/morbidity.

Hypernatremic donors was regarded as the expanded criteria donors in liver transplantation. The study was to investigate the effects of donor hypernatremia on the outcomes of liver transplantation and identify the prognostic factors possibly contributing to the poor outcomes.Donor serum sodium levels before procurement were categorized as normal sodium (155 mmol/L), moderate high sodium (155-170 mmol/L), and severe high sodium (≥ 170 mmol/L). Furthermore, we subdivided the 142 hypernatremic donors (≥ 155 mmol/L) into two subgroups: subgroup A, the exposure time of liver grafts from hypernatremia to reperfusion was36 h; and subgroup B, the exposure time was ≥ 36 h. The outcomes included initial graft function, survival rates of grafts and recipients, graft loss and early events within the first year following liver transplantation.There were no significant differences in the 1-year survival rates of grafts and recipients, 1-year graft loss rates and early events among the normal, moderate high and severe high sodium groups. However, the overall survival rates of grafts and recipients in subgroup A were significantly higher than those in subgroup B. Cox model showed that the exposure time (HR = 1.117; 95% CI: 1.053-1.186; P 0.001), cold ischemia time (HR = 1.015; 95% CI: 1.006-1.024; P = 0.001) and MELD (HR = 1.061; 95% CI: 1.003-1.121; P = 0.037) were the important prognostic factors contributing to the poor outcomes of recipients with hypernatremic donors.The level of donor sodium immediately before organ procurement does not have negative effects on the early outcomes following adult liver transplantation. For hypernatremia liver donors, minimization of the exposure time from hypernatremia to reperfusion is critical to prevent graft loss.

Height explains a substantial proportion of gender-based disparity in waitlist mortality among liver transplant candidates. We sought to identify a clinically relevant height cutoff below which waitlist mortality increases significantly. We examined all nonstatus one adult liver transplant candidates from 2010 to 2014. We used a recursive application of the minimum P value approach with univariate competing risk regressions (deceased donor liver transplantation as the competing risk) to detect differences in waitlist mortality with regards to height. Of 69 883 candidates, 36% (24 819) were women and 64% (45 064) were men. Median height for all was 173 cm: 163 cm in women, 178 cm in men. The optimal search method of recursively evaluating smaller height intervals yielded 166 cm as the optimal height cutoff. Using height

Background Fluconazole represents a common antifungal option for the treatment of Candida infections in liver transplant recipients. Although adequate antifungal exposure is known to correlate with favorable outcomes in patients with invasive candidiasis, therapeutic drug monitoring (TDM) of fluconazole is currently not recommended. Methods We conducted a retrospective study including adult liver transplant recipients receiving fluconazole for invasive candidiasis and undergoing TDM. We assessed the correlation between clinical variables, fluconazole trough plasma levels (Cmin ), and outcome. Results Twenty-seven patients (74% males; median age 57 years) were included. Abdominal candidiasis was the most frequent infection (56%). Median duration of fluconazole therapy was 17 days (IQR 9-21). Fluconazole median Cmin was 11.0 mg/L (range 2.4-30.6 mg/L). Five (19%) patients required TDM-guided fluconazole dose increase. All-cause in hospital mortality was 33%. Fluconazole Cmin >11 mg/L significantly correlated with clinical success (OR 8.78, 95% CI 1.13-67.8, P = 0.04). Conclusions Our study identified decreased fluconazole Cmin as a factor associated with negative outcomes in liver transplant recipients with Candida infection. TDM of fluconazole may be advisable in this patient population.

Functional impairment is associated with mortality in adult liver transplant candidates. This has not been studied in pediatric liver transplant candidates. United Network for Organ Sharing Standard Transplant Analysis and Research files were used to investigate functional status, waitlist mortality, and posttransplant outcomes in children younger than 18 years who were waitlisted in 2006-2016 for primary liver transplant. Functional status was categorized, by using the Lansky Play-Performance Scale (LPPS), as normal/good (80-100), moderately impaired (50-70), or severely impaired (10-40) by center assessment. Among 3250 children not listed as Status 1A, 62% had an LPPS score of 80-100, 25% had a score of 50-70, and 13% had a score of 10-40 at listing. Children with an LPPS score of 10-40 at listing were more likely to die while on the waitlist (standardized hazard ratio 1.85, 95% confidence interval 1.09-3.13, P=.02) in analyses adjusting for being on a ventilator, breathing support, or dialysis and other illness severity measures. For the 2565 children transplanted, an LPPS score of 10-40 at listing drastically increased mortality risk by 1year posttransplant (hazard ratio 5.77, 95% confidence interval 3.05-10.91, P&nbsp

Background. Recurrence of hepatocellular carcinoma (HCC) is an important predictor of survival after liver transplantation (LT). Recent studies show that early diagnosis, aggressive treatment, and surveillance may improve outcomes after HCC recurrence. We sought to determine the current practices and policies regarding surveillance for HCC recurrence after LT. Methods. We conducted a web-based national survey of adult liver transplant centers in the United States to capture center-specific details of HCC surveillance post-LT. Responses were analyzed to generate numerical and graphical summaries. Results. Of 101 eligible adult liver transplant centers, 48 (48%) centers across the United States responded to the survey. Among the participating centers, 79% stratified transplant recipients for HCC recurrence risk, while 19% did not have any risk stratification protocol. Explant microvascular invasion (mVI) was the most common factor used in risk stratification. Use of pretransplant serum biomarkers such as alpha-fetoprotein (AFP) was variable, with only 48% of the participating centers reporting specific “cutoff” values. While a majority of centers (88%) reported having a routine imaging protocol for HCC recurrence surveillance, there was considerable heterogeneity in terms of frequency and duration of such surveillance. Of the centers that did risk stratify patients to identify those at higher risk of HCC recurrence, about 50% did not change their surveillance protocol. Conclusions. Our study affirms significant variability in center practices, and our results reflect the need for high-quality studies to guide risk stratification and surveillance for HCC recurrence.

Purpose To determine computed tomographic (CT) features of primary graft nonfunction (PNF) after liver transplantation in comparison with those of early graft failure or death by identifiable causes. Materials and Methods Institutional review board approval was obtained and informed consent was waived. Among 3947 adult liver transplantations performed in one institution between May 2002 and May 2015, 72 patients died or had graft failure within 10 days, and 38 of them were evaluated with CT. PNF was diagnosed in 21 patients. The other 17 patients who died or had early graft failure were considered the non-PNF control group. On unenhanced CT images, graft attenuation was compared qualitatively. Graft attenuation was measured quantitatively and, if available, the difference between preoperative and postoperative CT (interval change) attenuation was evaluated. Unenhanced CT was evaluated for relative parenchymal enhancement. Statistical analyses included the Fisher exact and χ2 tests with Yates correction and the Student t test. Results On unenhanced CT images, grafts with PNF more commonly showed low (eight of 26 [31%]) or extremely low (18 of 26 [69%]) qualitative attenuation compared with grafts in the non-PNF group (three of 21 [14%], one of 21 [5%]; P < .001). The mean attenuation value (30.5 HU ± 10.8) was significantly lower and the mean interval change (24.7 HU ± 12.5) was significantly higher in the PNF group than in the non-PNF group (49.7 HU ± 8.0 and 9.7 HU ± 10.1, respectively; P < .001 and P = .001). There was no significant difference in the proportion of grafts that showed poor enhancement on postcontrast CT images between the PNF group and the non-PNF group (nine of 24 [38%] vs two of 20 [10%], respectively; P = .08). Conclusion Recipients with PNF after liver transplantation tended to show low or extremely low attenuation on unenhanced CT images, and this finding was seen more frequently in patients with PNF than in those who died of identifiable causes and in those with early graft failure. © RSNA, 2016 Online supplemental material is available for this article.

The number of liver grafts obtained from a cadaver can be greatly increased with the application of split liver transplantation. In the last 10 years, pediatric waiting list mortality has been reduced significantly with the use of this form of liver transplantation, which has 2 major forms. In its most commonly used form, the liver can be transplanted into 1 adult and 1 child by splitting it into a right extended and a left lateral graft. For adult and pediatric recipients, the results of this procedure are comparable to those of whole-organ techniques. In another form, 2 hemi-grafts are obtained by splitting the liver, which can be transplanted into a medium-sized adult (the right side) and a large child/small adult (the left side). The adult liver graft pool is expanded through the process of full right/full left splitting; but it is also a critical technique when one considers the knowledge required of the potential anatomic variations and the high technical skill level needed. In this review, we provide some basic insights into the technical and anatomical aspects of these 2 forms of split liver transplantation and present an updated summary of both forms.

Background Diverse tacrolimus population pharmacokinetic (popPK) models in adult liver transplant recipients have been established to describe the PK characteristics of tacrolimus in the last two decades. However, their extrapolated predictive performance remains unclear. Therefore, in this study, we aimed to evaluate their external predictability and identify their potential influencing factors. Methods The external predictability of each selected popPK model was evaluated using an independent dataset of 84 patients with 572 trough concentrations prospectively collected from Huashan Hospital. Prediction- and simulation-based diagnostics and Bayesian forecasting were conducted to evaluate model predictability. Furthermore, the effect of model structure on the predictive performance was investigated. Results Sixteen published popPK models were assessed. In prediction-based diagnostics, the prediction error within ± 30% was below 50% in all the published models. The simulation-based normalised prediction distribution error test and prediction- and variability-corrected visual predictive check indicated large discrepancies between the observations and simulations in most of the models. Bayesian forecasting showed improvement in model predictability with two to three prior observations. Additionally, the predictive performance of the nonlinear Michaelis–Menten model was superior to that of linear one- and two-compartment models with first-order elimination, indicating the underlying nonlinear kinetics of tacrolimus in liver transplant recipients, which was consistent with the findings in adult kidney transplant recipients. Conclusions The published models performed inadequately in prediction- and simulation-based diagnostics. Bayesian forecasting may improve the predictive performance of the models. Furthermore, nonlinear kinetics of tacrolimus may be mainly caused by the properties of the drug itself, and incorporating nonlinear kinetics may be considered to improve model predictability.

Livers from older donors (OLDs; age ≥70) are risky and often declined; however, it is likely that some candidates will benefit from OLDs versus waiting for younger ones. To characterize the survival benefit of accepting OLD grafts, we used 2009-2017 SRTR data to identify 24 431 adult liver transplant (LT) candidates who were offered OLD grafts eventually accepted by someone. Outcomes from the time-of-offer were compared between candidates who accepted an OLD graft and matched controls within MELD ± 2 who declined the same offer. Candidates who accepted OLD grafts (n = 1311) were older (60.5 vs. 57.8 years, P < .001), had a higher median MELD score (25 vs. 22, P < .001), and were less likely to have hepatitis C cirrhosis (14.9% vs. 31.2%, P < .001). Five-year cumulative mortality among those who accepted versus declined the same OLD offer was 23.4% versus 41.2% (P < .001). Candidates who accepted OLDs experienced an almost twofold reduction in mortality (aHR:0.45 0.520.59 , P < .001) compared to those who declined the same offer, especially among the highest MELD (35-40) candidates (aHR:0.10 0.240.55 , P = .001). Accepting an OLD offer provided substantial long-term survival benefit compared to waiting for a better organ offer, notably among candidates with MELD 35-40. Providers should consider these benefits as they evaluate OLD graft offers.

Background The field of transplantation is shifting outcome priorities from 1-year survival to more comprehensive metrics including transplant rate and waitlist mortality. Identifying disenfranchised candidates (high waitlist death risk, low transplantation chance) can be a focus to improve outcomes. Methods Given the waitlist outcomes (continued waiting, death, and transplantation), we aimed to identify factors predicting the likelihood candidates would undergo transplant or death by performing multivariate competing risk analyses of 121 198 candidates in the United Network for Organ Sharing database. We incorporated these probabilities (likelihood of transplantation and waitlist death) into the Transplant Index (TI) to identify disenfranchised candidates (high likelihood of death, low likelihood of transplantation). Results Half of the patients had low incidences of death and transplantation within 90 days (TI-inactive). The remaining were stratified into 10 groups within a predictive index, the TI. Low TI groups (TI 10, 20, 30) had 90-day transplant rates of 50.8%, 41.6%, and 39.8% respectively, and their respective 90-day death rates were 22.8%, 15.1%, and 10.9%. High TI groups (TI 80, 90, >90) had 90-day transplantation rates of 53.7%, 64.3%, and 73.9%, respectively, and 90-day death rates of 5.9%, 6.5%, and 6.7% respectively. As TI increased, the likelihood of transplantation increased and that of death decreased. Low-TI groups represent the disenfranchised candidates. Conclusions The TI identifies disenfranchised candidates on the adult liver transplant waitlist. This is the subgroup that would benefit the most from efforts to increase access to transplantation.

Splitting deceased donor livers and creating 3 grafts from a whole liver may be feasible and shorten the waiting time for organ donation in patients with high mortality rates. We hypothesized that it might be reasonable to procure 3 grafts for donation from one deceased donor liver by splitting the liver into left (segment II, III, IV), right anterior (segment V, VIII), and right posterior lobes (segment VI, VII) for liver transplantation according to the portal system trifurcated variations. We designed the right anterior branch with the main portal trunk and middle hepatic artery to become inflow of right anterior lobe, the left portal vein and left hepatic artery to become the inflow of left lobe and right posterior branch, and right hepatic artery to become the inflow of right posterior lobe. We retrospectively reviewed the volumetric computed tomography and magnetic resonance cholangiopancreatography of 153 liver donors. The hepatic and portal veins, hepatic artery, and biliary system were reorganized and classified. The volumetric proportions of the liver grafts were measured. Trifurcation of the portal vein variation was found in approximately 13.7% of portal systemic variations. The left lobe accounted for 29.18% of the total liver volume, the right anterior lobe, 35.22%, and the right posterior lobe, 35.6%. We validated this principle by dissecting the explanted liver and identified the triple grafts' weights, percentages, vessels, and biliary ducts system. The splitting of deceased donor livers into 3 split liver grafts for use in liver transplantation surgery can be clinically useful.

Purpose Herpes zoster (HZ) is caused by reactivation of the varicella zoster virus, which occurs frequently in liver transplant recipients with impaired cellular immunity. The purpose of this study was to evaluate the incidence and risk factors for HZ after adult liver transplantation (LT). Methods In our institution, 993 patients underwent adult LT from January 1997 to December 2013. We retrospectively analyzed the incidence rate of HZ and risk factors for HZ after LT. Results Of 993 LT recipients, 101 (10.2%) were diagnosed with HZ. The incidence of HZ at 1, 3, 5, and 10 years was 6.6%, 9.1%, 10.0%, and 11.9%, respectively. Therefore, we observed that the incidence of HZ after LT was 16.3 per 1,000 person-years. Older age (≥50 years) at LT and mycophenolate mofetil (MMF) exposure were independent risk factors of HZ infection after adult LT. Conclusion Patients older than 50 years or with MMF exposure are considered to be at high risk for HZ. Therefore, adult liver recipients with such factors should not be given strong immunosuppression treatments.

The transition of young adults (YA) from paediatric to adult health services is a challenging time for patients, parents / care providers and health care professionals. This period has a higher prevalence of mental health problems and is associated with high rates of non-adherence.[1][1] These

Elucidating the mechanical force-induced regulatory machineries is extremely important for further understanding of the mechanisms underlying development, regeneration, and disease. Recent work demonstrates that mechanical forces generated by blood flow in liver vessels function to regulate embryonic liver development and may also contribute to regeneration in adult liver.