Search

Background: The optimal cardiovascular assessment of liver transplant (LT) candidates is unclear. We aimed to evaluate the performance of CT-based coronary tests (coronary artery calcium score [CACS] and coronary CT angiography [CCTA]) and a modification of the CAD-LT score (mCAD-LT, excluding family history of CAD) to diagnose significant coronary artery disease (CAD) before LT and predict the incidence of post-LT cardiovascular events (CVE)., Methods: We retrospectively analysed a single-centre cohort of LT candidates who underwent non-invasive tests; invasive coronary angiography (ICA) was performed depending on the results of non-invasive tests. mCAD-LT was calculated in all patients., Results: Six-hundred-and-thirty-four LT candidates were assessed and 351 of them underwent LT. CACS, CCTA and ICA were performed in 245, 123 and 120 LT candidates, respectively. Significant CAD was found in 30% of patients undergoing ICA. The AUROCs of mCAD-LT (.722) and CCTA (.654) were significantly higher than that of CACS (.502) to predict the presence of significant CAD. Specificity of the tests ranged between 31% for CCTA and 53% for CACS. Among patients who underwent LT, CACS ≥ 400 and mCAD-LT were independently associated with the incidence of CVE; in patients who underwent CCTA before LT, significant CAD at CCTA also predicted post-LT CVE., Conclusion: In this cohort, mCAD-LT score and CT-based tests detect the presence of significant CAD in LT candidates, although they tend to overestimate it. Both mCAD-LT score and CT-based tests classify LT recipients according to their risk of post-LT CVE and can be used to improve post-LT risk mitigation., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)

Liver transplantation is the most effective treatment for end-stage liver disease. Transplant indications have been progressively increasing, with a huge discrepancy between the supply and demand of optimal organs. In this context, the use of extended criteria donor grafts has gained importance, even though these grafts are more susceptible to ischemic reperfusion injury (IRI). Hepatic IRI is an inherent and inevitable consequence of all liver transplants; it involves ischemia-mediated cellular damage exacerbated upon reperfusion and its severity directly affects graft function and post-transplant complications. Strategies for organ preservation have been constantly improving since they first emerged. The current gold standard for preservation is perfusion solutions and static cold storage. However, novel approaches that allow extended preservation times, organ evaluation, and their treatment, which could increase the number of viable organs for transplantation, are currently under investigation. This review discusses the mechanisms associated with IRI, describes existing strategies for liver preservation, and emphasizes novel developments and challenges for effective organ preservation and optimization.

Background: The management of liver transplantation has become a complex process involving different healthcare professionals. Teamwork, standardisation and definition of the best practices are essential for success, patient satisfaction and society's favourable perception of transplantation programmes.ISO 9001:2015 certification provides the necessary elements to help implement a quality management system (QMS) to ensure that patient care is performed with the highest guarantees of clinical quality and safety. The aim of this study is to describe the steps, strengths and limitations in the implementation of a QMS in a liver transplant programme (LTP)., Project Management Method: This included analysing the starting point, setting up a working group, training, defining the scope of certification, preparing documentation, and conducting an internal and external audit, which culminated in the ISO 9001 quality certification award. The scope of QMS includes all the processes of LTP, from referral of candidates to long-term follow-up after transplantation., Results: The project was structured in seven phases that took place between 2008 and 2011. The implementation of QMS led to the generation of all the necessary documentation to meet the requirements of the standard, including internal and legal requirements related to the transplant activity. The establishment of indicators to measure the effectiveness of processes, risk management and the identification of incidents allows us to implement measures devoted to avoiding the deficiencies and to meet the established objectives., Conclusion: ISO 9001:2015 certification has contributed to the adaptation of a new quality and safety culture focused on the patient. All activities are protocolised, everything is recorded, measured, and verified, and all steps are taken as planned. Work is carried out in terms of continuous improvement. This has led to less variability in daily clinical practice and a better understanding of work dynamics., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Over the last 50 years, liver transplantation has evolved into a procedure routinely performed in many countries worldwide. Those able to access this therapy frequently experience a miraculous risk-benefit ratio, particularly if they face the imminently life-threatening disease. Over the decades, the success of liver transplantation, with dramatic improvements in early posttransplant survival, has aggressively driven demand. However, despite the emergence of living donors to augment deceased donors as a source of organs, supply has lagged far behind demand. As a result, rationing has been an unfortunate focus in recent decades. Recent shifts in the epidemiology of liver disease combined with transformative innovations in liver preservation suggest that the underlying premise of organ shortage may erode in the foreseeable future. The focus will sharpen on improving equitable access while mitigating constraints related to workforce training, infrastructure for organ recovery and rehabilitation, and their associated costs. Research efforts in liver preservation will undoubtedly blossom with the aim of optimizing both the timing and conditions of transplantation. Coupled with advances in genetic engineering, regenerative biology, and cellular therapies, the portfolio of innovation, both broad and deep, offers the promise that, in the future, liver transplantation will not only be broadly available to those in need but also represent a highly durable life-saving therapy., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: More than a half of patients undergoing liver transplantation (LT) receive intraoperative transfusion. Portal hypertension (PHT) may contribute to perioperative blood loss. We study the relationship between preoperative hepatic venous pressure gradient (HVPG) values and intraoperative transfusion requirements in adult patients undergoing LT., Methods: 160 cirrhotic patients undergoing first elective LT (2009-2019) with an HVPG measurement within the previous 6 months were included. Surgical technique was piggyback with portocaval shunt (PCS). The association of HVPG and other variables with transfusion requirements and blood loss were studied., Results: Blood loss (ml/kg) was positively correlated with HVPG, among other variables, but at multivariable analysis it only remained associated with MELD-Na and HCC indication. Regarding RBC transfusion, MELD-Na and hemoglobin were independently associated with the need and magnitude of RBC transfusion. Subanalysis by surgical stage (hepatectomy, anhepatic, neohepatic) and by serial HVPG cut-offs found no clear associations with either bleeding or transfusion., Discussion: The severity of PHT plays a minor role on bleeding and transfusion during LT in a contemporary cohort with systematic PCS. Main determinants of transfusion are liver function and baseline hemoglobin, which would seem the suitable goal to optimize transfusion in LT., Competing Interests: Disclosures The authors disclose no conflicts of interest., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

This review discusses long-term complications from immunosuppressants after liver transplantation and the management of these complications. Common complications of calcineurin inhibitors include nephrotoxicity and metabolic diseases. Nephrotoxicity can be managed by targeting a lower drug level and/or adding an immunosuppressant of a different class. Metabolic disorders can be managed by treating the underlying condition and targeting a lower drug level. Gastrointestinal adverse effects and myelosuppression are common complications of antimetabolites that are initially managed with dose reduction or discontinuation if adverse events persist. Mammalian targets of rapamycin inhibitors are associated with myelosuppression, proteinuria, impaired wound healing, and stomatitis, which may require dose reduction or discontinuation. Induction agents and agents used for steroid-refractory rejection or antibody-mediated rejection are reviewed. Other rare complications of immunosuppressants are discussed as well., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Although liver transplantation (LT) recipients are at high cardiovascular risk (CVR), the management of CVR factors (CVRF) after LT is far from optimal and needs to be improved. For this reason, we developed a multidisciplinary protocol to standardize the identification, risk stratification, management, and targets of therapy of CVRF during the first post-LT year. The grade of identification and control of CVRF 12 months after LT in the postintervention cohort (LT January 2018-January 2020, n = 150) were compared with a control cohort who underwent LT between July 2015 and December 2016 (n = 100). Before LT, the prevalence of metabolic-associated fatty liver disease as the indication of LT and the presence of obesity were significantly higher in the postintervention cohort, whereas the prevalence of other CVRF and renal dysfunction tended to be higher. Cyclosporine A was used less frequently in the postintervention cohort, whereas everolimus tended to increase. At 12 months after LT, the proportion of patients with measured blood pressure (88% vs. 56%), glycosilated hemoglobin (HbA1c; 96% vs. 72%), and high-density lipoprotein/low-density lipoprotein cholesterol (67% vs. 33%) was higher in the postintervention than in the control cohort (all p < 0.001). Blood pressure (64% vs. 36%, p = 0.02) and HbA1c (85% vs. 70%, p = 0.1) were within target in more individuals with hypertension and diabetes mellitus, respectively, in the postintervention cohort. Median total cholesterol levels were lower in the postintervention (184 mg/dl; interquartile range [IQR], 160-210 mg/dl) than in the control cohort (212 mg/dl; IQR, 186-240 mg/dl; p = 0.02). At 2 years after LT, the incidence of cardiovascular events was 14% in the control cohort and 6% in the postintervention cohort (p = 0.063). In conclusion, a multidisciplinary, multiprofessional strategy can achieve a higher grade of assessment and management of post-LT CVR despite a worsening metabolic profile of LT recipients., (© 2022 American Association for the Study of Liver Diseases.)

Background: A difficulty score to predict intraoperative surgical complexity in liver transplantation has never been developed. The aim of this study was to assess factors associated with a difficult liver transplant and develop a score to predict difficult surgery., Methods: All patients undergoing deceased donor whole liver transplantation from 2012 to 2019 at a single center were included. Estimated intraoperative blood loss (mL/kg) and surgery duration (skin-to-arterial reperfusion time) were used as surrogates of difficulty. Based on these variables, the study population was divided into 2 groups: high risk and standard risk of difficulty. Univariate and multivariate analyses were performed to identify predictors associated with a demanding liver transplantation and develop a difficulty score., Results: A total of 515 patients were included in the study population, and 101 (20%) were considered difficult operations. Patients with a higher risk of difficulty showed a significantly higher rate of Clavien-Dindo ≥III complications (50.5% vs 24.4%, P = .001) and a longer hospital stay (19 vs 16 days, P = .001). Preoperative factors associated with difficulty were retransplantation (odds ratio 4.34, P = .001), preoperative portal vein thrombosis (odds ratio 3.419, P = .001), previous upper abdominal surgery (odds ratio 2.161, P = .003), spontaneous bacterial peritonitis (odds ratio 1.985, P &lt; .02), and prior variceal bleeding (odds ratio 1.401, P = .051). A 10-point difficulty score was created, showing a negative predictive value of 84% at 4 points., Conclusion: Difficult liver transplantation surgery, as assessed by skin-to-arterial reperfusion time and estimated blood loss, is associated with worse perioperative outcomes. We developed a simple score with clinical preoperative variables that predicts difficult surgery, and therefore, it may help to optimize allocation policies and perioperative logistics., (Copyright © 2022 Elsevier Inc. All rights reserved.)

There is growing evidence that liver transplantation (LT) is the most effective treatment for acute-on-chronic liver failure grade-3 (ACLF-3). This study examines whether and how this evidence translates into practice by analyzing the variability in intensive care unit (ICU) admissions, listing strategies, and LT activity for patients with ACLF-3 across transplantation centers in Europe. Consecutive patients who were admitted to the ICU with ACLF-3, whether or not they were listed and/or transplanted with ACLF-3, between 2018 and 2019 were included across 20 transplantation centers. A total of 351 patients with ACLF-3 were included: 33 had been listed prior to developing ACLF-3 and 318 had not been listed at the time of admission to the ICU. There was no correlation between the number of unlisted patients with ACLF-3 admitted to the ICU and the number listed or transplanted while in ACLF-3 across centers. By contrast, there was a correlation between the number of patients listed and the number transplanted while in ACLF-3. About 21% of patients who were listed while in ACLF-3 died on the waiting list or were delisted. The percentage of LT for patients with ACLF-3 varied from 0% to 29% for those transplanted with decompensated cirrhosis across centers (average = 8%), with an I 2 index of 68% (95% confidence interval, 49%-80%), showing substantial heterogeneity among centers. The 1-year survival for all patients with ACLF-3 was significantly higher in centers that listed and transplanted more patients with ACLF-3 (>10 patients) than in centers that listed and transplanted fewer: 36% versus 20%, respectively (p = 0.012). Patients with ACLF-3 face inequity of access to LT across Europe. Waitlisting strategies for patients with ACLF-3 influence their access to LT and, ultimately, their survival., (© 2022 American Association for the Study of Liver Diseases.)

The International Liver Transplantation Society and the Spanish Society of Liver Transplantation consensus conference on extrahepatic cancer and liver transplantation (LT) was held on January 28-30, 2021. Working groups were organized to focus on one topic and develop evidence-based recommendations specifically addressing (a) nonhepatic cancer in LT candidates, (b) de novo malignancies after LT, (c) prevention and management of donor-derived malignancies after LT, and (d) nonhepatic cancer in the pediatric population. All consensus conference attendees voted on the recommendations proposed as well as the quality of evidence according to the Grading of Recommendations, Assessment, Development and Evaluation system., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Anticoagulation and antiplatelet therapies are increasingly used in liver transplant (LT) candidates and recipients due to cardiovascular comorbidities, portal vein thrombosis, or to manage posttransplant complications. The implementation of the new direct-acting oral anticoagulants and the recently developed antiplatelet drugs is a great challenge for transplant teams worldwide, as their activity must be monitored and their complications managed, in the absence of robust scientific evidence. In this changing and clinically heterogeneous scenario, the Spanish Society of Liver Transplantation and the Spanish Society of Thrombosis and Haemostasis aimed to achieve consensus regarding the indications, drugs, dosing, and timing of anticoagulation and antiplatelet therapies initiated from the inclusion of the patient on the waiting list to post-LT surveillance. A multidisciplinary group of experts composed by transplant hepatologists, surgeons, hematologists, transplant-specialized anesthesiologists, and intensivists performed a comprehensive review of the literature and identified 21 clinically relevant questions using the patient-intervention-comparison-outcome format. A preliminary list of recommendations was drafted and further validated using a modified Delphi approach by a panel of 24 transplant delegates, each representing a LT institution in Spain. The present consensus statement contains the key recommendations together with the core supporting scientific evidence, which will provide guidance for improved and more homogeneous clinical decision making., Competing Interests: A.B. has received a lecture fee from Octapharma. The remaining authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Cancer is the leading cause of death after liver transplantation (LT). This multicenter case-control nested study aimed to evaluate the effect of maintenance immunosuppression on post-LT malignancy. The eligible cohort included 2495 LT patients who received tacrolimus-based immunosuppression. After 13 922 person/years follow-up, 425 patients (19.7%) developed malignancy (cases) and were matched with 425 controls by propensity score based on age, gender, smoking habit, etiology of liver disease, and hepatocellular carcinoma (HCC) before LT. The independent predictors of post-LT malignancy were older age (HR = 1.06 [95% CI 1.05-1.07]; p < .001), male sex (HR = 1.50 [95% CI 1.14-1.99]), smoking habit (HR = 1.96 [95% CI 1.42-2.66]), and alcoholic liver disease (HR = 1.53 [95% CI 1.19-1.97]). In selected cases and controls (n = 850), the immunosuppression protocol was similar (p = .51). An increased cumulative exposure to tacrolimus (CET), calculated by the area under curve of trough concentrations, was the only immunosuppression-related predictor of post-LT malignancy after controlling for clinical features and baseline HCC (CET at 3 months p = .001 and CET at 12 months p = .004). This effect was consistent for de novo malignancy (after excluding HCC recurrence) and for internal neoplasms (after excluding non-melanoma skin cancer). Therefore, tacrolimus minimization, as monitored by CET, is the key to modulate immunosuppression in order to prevent cancer after LT., (© 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Antivitamin K agent (AVK) reversal in patients with cirrhosis awaiting liver transplantation (LT) is not defined in guidelines. We investigated the effect of reversion with prothrombin complex concentrate (PCC) on intraoperative transfusion, bleeding, and safety in LT patients on AVK., Study Design and Methods: In 511 patients undergoing LT, we identified 25 patients treated with AVK (AVK group) and 13 patients with incidental portal vein thrombosis (PVT) without AVK (incidental PVT group). Fifty patients who underwent LT without PVT or AVK matched by age, model for end stage of liver disease (MELD), body mass index (BMI), and cirrhosis etiology were selected as the control group., Results: There were no significant differences between the three groups in intraoperative blood loss, transfusion, and postoperative bleeding. In the AVK group, there were no differences between patients who received PCC and those who did not in intraoperative blood loss, red blood cells, fibrinogen, and platelet transfusion, or postoperative bleeding. PCC use had no effect on RBC transfusion in patients who had international normalized ratio or clotting time above versus below median values of the two parameters at baseline (2.3 and 103 s, respectively). No thrombotic events were detected in patients who received PCC., Discussion: These data suggest that systematic administration of PCC to revert AVK prior to LT should be reconsidered., (© 2021 AABB.)

De novo malignancies (DNMs) following liver transplantation (LT) have been reported as 1 of the major causes of late mortality, being the most common cause of death in the second decade after LT. The overall incidence of DNMs is reported to be in the range of 3.1% to 14.4%, and the incidence is 2- to 3-fold higher in transplant recipients than in age- and sex-matched healthy controls. Long-term immunosuppressive therapy, which is the key in maintaining host tolerance and achieving good long-term outcomes, is known to contribute to a higher risk of DNMs. However, the incidence and type of DNM also depends on different risk factors, including patient demographics, cause of the underlying chronic liver disease, behavior (smoking and alcohol abuse), and pre-existing premalignant conditions. The estimated standardized incidence ratio for different DNMs is also variable. The International Liver Transplantation Society-Spanish Society of Liver Transplantation Consensus Conference working group on DNM has summarized and discussed the current available literature on epidemiology, risk factors, management, and survival after DNMs. Recommendations for screening and surveillance for specific tumors, as well as immunosuppression and cancer-specific management in patients with DNM, are summarized., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Controlled donation after circulatory death (cDCD) has expanded the donor pool for liver transplantation (LT). However, transfusion requirements and perioperative outcomes should be elucidated. The aim of this multicenter study was to assess red blood cell (RBC) transfusions, one-year graft and patient survival after LT after cDCD with normothermic regional perfusion (NRP) compared with donors after brain death (DBD)., Methods: 591 LT carried out in ten centers during 2019 were reviewed. Thromboelastometry was used to manage coagulation and blood product transfusion in all centers. Normothermic regional perfusion was the standard technique for organ recovery., Results: 447 patients received DBD and 144 cDCD with NRP. Baseline MCF Extem was lower in the cDCD group There were no differences in the percentage of patients (63% vs. 61% p = 0.69), nor in the number of RBC units transfused (4.7 (0.2) vs 5.5 (0.4) in DBD vs cDCD, p = 0.11. Twenty-six patients (6%) died during admission for LT in the DBD group compared with 3 patients (2%) in the cDCD group (p = 0.15). To overcome the bias due to a worse coagulation profile in cDCD recipients, matched samples were compared. No differences in baseline laboratory data, or in intraoperative use of RBC or one-year outcome data were observed between DBD and cDCD recipients., Conclusions: cDCD with NRP is not associated with increased RBC transfusion. No differences in graft and patient survival between cDCD and DBD were found. Donors after controlled circulatory death with NRP can increasingly be utilized with safety, improving the imbalance between organ donors and the ever-growing demand., (Copyright © 2021 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Uhl's anomaly is an extremely rare congenital heart defect characterized by absence of the right ventricle myocardium and preserved left ventricular myocardium. Although the disease has a poor prognosis and is generally fatal in the perinatal period, some patients may reach adulthood., Methods: We describe a case of Uhl's anomaly complicated with heart failure and decompensated cardiac cirrhosis in a 42-year-old man treated by combined heart-liver transplant., Results: The patient underwent heart transplant using the bicaval technique followed by subsequent liver transplant with the piggyback technique without venovenous bypass. Total ischemia time was 108 minutes for the heart and 360 and 25 minutes of cold and warm ischemia, respectively, for the liver. No intraoperative complications occurred. The patient was discharged without severe complications on postoperative day 22. Pathologic examination of the organs reported advanced cirrhosis of the liver and severe dilated myocardiopathy of right ventricle with absence of myocardium and a normal left ventricle. Twenty-seven months after the transplant the patient has been free from hospital admissions, with normal function of both transplanted organs., Conclusions: We report the first successful combined heart-liver transplant for Uhl's anomaly indication in an adult patient. Despite of the insufficient knowledge of natural history of this exceptional disease, we successfully apply the management principles of other end-stage right heart disorders complicated with liver failure., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To evaluate the results of isolated liver and combined liver and kidney transplantation in a retrospective series of 32 patients with hepatorenal liver and kidney disease., Materials and Methods: A retrospective observational study that enrolled patients with polycystic liver disease (PLD) and polycystic liver and kidney disease (PLKD) who were evaluated for transplantation between January 1999 and December 2019 at Hospital Clínic de Barcelona [Clinical Hospital of Barcelona]., Results: We included a total of 53 patients enrolled, 32 (60.3%) had indication for transplantation, of which 12 received a single liver transplant and 20 received a double liver and kidney transplant. The mean age was 52 years and 83.9% of the recipients were women. The main indication for liver transplantation was disabling symptomatic hepatomegaly (93.5%). Among the postoperative complications, in the combined liver and kidney transplant group, hepatic artery thrombosis in one case and renal artery thrombosis in other were detected. In both groups there was one case of inferior vena cava lesion. Three patients presented acute cellular rejection responding to corticosteroids and one presented humoral rejection which was treated with plasmapheresis. During the follow-up period of 80 (27-121) months, the liver transplant survival rate was 100% and the kidney transplant survival rate was 90%. Two patients in the combined liver and kidney transplant group died (one due to cardiovascular causes and the other due to intestinal adenocarcinoma)., Conclusions: Isolated liver transplantation or combined liver and kidney transplantation in selected patients with polycystic disease yields excellent results, with few complications, very good transplant survival and excellent patient survival (93.8%)., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

Objectives: Our study aims to explore the clinical characteristics of Omicron infection in pediatric liver transplant recipients (PLTRs), after the national COVID-19 outbreak. Additionally, we will investigate changes in vaccine coverage and parental attitudes towards vaccinating their children after this current outbreak., Methods: We conducted a web-based questionnaire survey to gather information on Omicron infection, vaccination status, and guardian attitude among PLTRs. Besides, utilized valid questionnaire and long-term follow-up information processing techniques, and performed statistical analysis of relevant parameters., Results: 528 valid questionnaires were collected, among which, 251 responses replied Omicron infection status. The Omicron infection rate in Chinese PLTRs was 56.2% (141/251), similar to the report in the normal population (around 60%). 99.3% of infected PLTRs presented mild symptoms, mostly with fever (78.0%), followed by Cough (76.6%), with a mean RTPCR conversion time of 7 days; the overall PLTRs' vaccination rate in this study was 13.3%, similar to that of our previous study (9.4%). Besides, we found no significant differences of either infection rate or clinical symptoms between the vaccinated and unvaccinated groups. Moreover, the study showed 61.6% of guardians supported COVID-19 inoculation despite the outbreak of Omicron status., Conclusions: The symptoms of Omicron infection in Chinese PLTRs were relatively mild, vaccine immunization had a limited effect on PLTRs' defense against Omicron infection, besides, their guardians supported the inoculation policy with a caution., Clinical Trial Registration: http://www.chictr.org.cn , identifier ChiCTR2200055968., Competing Interests: Declarations. Ethics approval and consent to participate: The Ethics Committee of Renji Hospital, Shanghai Jiao Tong University School of Medicine has sanctioned our study. All participants were thoroughly informed about the survey and gave their full consent to participate before completing the questionnaire. Consent for publication: All authors have consented to publication. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Liver transplantation (LT) is the most successful treatment for patients with decompensated cirrhosis. The availability of effective and safe etiological treatments has altered the natural history of decompensated cirrhosis. Recently, the concept of recompensation has been defined. Patients who achieve recompensation may be removed from the waiting list for LT. Therefore, achieving an etiological cure is the cornerstone in the treatment of patients with decompensated cirrhosis. However, most patients improve their liver function after an etiologic cure, and only a proportion of patients achieve true recompensation after an etiological cure. Some patients maintain a condition of "MELD purgatory," that is, an improvement in the Model for End-Stage Liver Disease score without relevant clinical improvement that prevents delisting and may be even detrimental because lower Model for End-Stage Liver Disease score delays LT. Herein, we review the available evidence regarding recompensation and the management of recompensated patients on the waiting list for LT., (Copyright © 2024 American Association for the Study of Liver Diseases.)

The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case-control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p < .001) and at 6 months (63.4% vs. 90.1%, p < .001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p = .001) and 6 months (p < .001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17-83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03-1.36), and therapy with renin-angiotensin-aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47-34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background & Aims: To what extent patients with alcohol-related decompensated cirrhosis can improve until recovery from decompensation remains unclear. We aimed to investigate the probability of recovery and delisting due to improvement in patients with alcohol-related decompensated cirrhosis on the waiting list (WL) for liver transplantation (LT)., Methods: We conducted a registry-based, multicenter, retrospective study including all patients admitted to the LT WL in Catalonia (Spain) with the indication of alcohol-, HCV-, cholestasis- or non-alcoholic steatohepatitis-related decompensated cirrhosis between January 2007 and December 2018. Competing-risk analysis was used to investigate variables associated with delisting due to improvement in patients with alcohol-related decompensated cirrhosis. Criteria for delisting after improvement were not predefined. Outcomes of patients after delisting were also studied., Results: One-thousand and one patients were included, 420 (37%) with alcohol-related decompensated cirrhosis. Thirty-six (8.6%) patients with alcohol-related decompensated cirrhosis were delisted after improvement at a median time of 29 months after WL admission. Lower model for end-stage liver disease (MELD) score, higher platelets and either female sex or lower height were independently associated with delisting due to improvement, while time of abstinence did not reach statistical significance in multivariate analysis (p = 0.055). Five years after delisting, the cumulative probability of remaining free from liver-related death or LT was 76%, similar to patients with HCV-related decompensated cirrhosis delisted after improvement., Conclusions: A significant proportion of LT candidates with alcohol-related cirrhosis can be delisted due to improvement, which is predicted by low MELD score and higher platelet count at WL admission. Women also have a higher probability of being delisted after improvement, partially due to reduced early access to LT for height discrepancies. Early identification of patients with potential for improvement may avoid unnecessary transplants., Lay Summary: Patients with alcohol-related cirrhosis can improve until being delisted in approximately 9% of cases. Low model for end-stage liver disease score and high platelet levels at admission predict delisting after improvement, and women have higher probabilities of being delisted due to improvement. Long-term outcomes after delisting are generally favorable., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Recurrent attacks of acute intermittent porphyria (AIP) result in poor quality of life and significant risks of morbidity and mortality. Liver transplantation (LT) offers a cure, but published data on outcomes after LT are limited. We assessed the pretransplant characteristics, complications, and outcomes for patients with AIP who received a transplant. Data were collected retrospectively from the European Liver Transplant Registry and from questionnaires sent to identified transplant and porphyria centers. We studied 38 patients who received transplants in 12 countries from 2002 to 2019. Median age at LT was 37 years (range, 18-58), and 34 (89%) of the patients were women. A total of 9 patients died during follow-up, and 2 patients were retransplanted. The 1-year and 5-year overall survival rates were 92% and 82%, which are comparable with other metabolic diseases transplanted during the same period. Advanced pretransplant neurological impairment was associated with increased mortality. The 5-year survival rate was 94% among 19 patients with moderate or no neuropathy at LT and 83% among 10 patients with severe neuropathy (P = 0.04). Pretransplant renal impairment was common. A total of 19 (51%) patients had a GFR < 60 mL/minute. Although few patients improved their renal function after LT, neurological impairments improved, and no worsening of neurological symptoms was recorded. No patient had AIP attacks after LT, except for a patient who received an auxiliary graft. LT is a curative treatment option for patients with recurrent attacks of AIP. Severe neuropathy and impaired renal function are common and increase the risk for poor outcomes. If other treatment options fail, an evaluation for LT should be performed early., (Copyright © 2020 The Authors. Liver Transplantation published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background and Aims: Despite concerns that liver transplant (LT) recipients may be at increased risk of unfavorable outcomes from COVID-19 due the high prevalence of co-morbidities, immunosuppression and ageing, a detailed analysis of their effects in large studies is lacking., Methods: Data from adult LT recipients with laboratory confirmed SARS-CoV2 infection were collected across Europe. All consecutive patients with symptoms were included in the analysis., Results: Between March 1 and June 27, 2020, data from 243 adult symptomatic cases from 36 centers and 9 countries were collected. Thirty-nine (16%) were managed as outpatients while 204 (84%) required hospitalization including admission to the ICU (39 of 204, 19.1%). Forty-nine (20.2%) patients died after a median of 13.5 (10-23) days, respiratory failure was the major cause. After multivariable Cox regression analysis, age >70 (HR, 4.16; 95% CI, 1.78-9.73) had a negative effect and tacrolimus (TAC) use (HR, 0.55; 95% CI, 0.31-0.99) had a positive independent effect on survival. The role of co-morbidities was strongly influenced by the dominant effect of age where comorbidities increased with the increasing age of the recipients. In a second model excluding age, both diabetes (HR, 1.95; 95% CI, 1.06-3.58) and chronic kidney disease (HR, 1.97; 95% CI, 1.05-3.67) emerged as associated with death CONCLUSIONS: Twenty-five percent of patients requiring hospitalization for COVID-19 died, the risk being higher in patients older than 70 and with medical co-morbidities, such as impaired renal function and diabetes. Conversely, the use of TAC was associated with a better survival thus encouraging clinicians to keep TAC at the usual dose., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The number of patients awaiting liver transplantation (LT) in Spain has halved from 2015 to 2019 due to the reduction of candidates with hepatitis C and the successful implementation of nonheart beating donation programs across the country. The Spanish Society for Liver Transplantation has committed to take advantage of this situation by developing consensus around potential areas to expand the current indications for LT. The consensus group was composed of 6 coordinators and 23 expert delegates, each one representing an LT institution in Spain., Methods: A modified Delphi approach was used to identify areas to expand indications for LT and to build consensus around paramount aspects, such as inclusion criteria and waitlist prioritization within each area. The scientific evidence and strength of recommendations were assessed by the "Grading of Recommendations Assessment, Development, and Evaluation" system., Results: The consensus process resulted in the identification of 7 potential areas to expand criteria in LT: recipient's age, hepatocellular carcinoma, alcoholic hepatitis, acute-on-chronic liver failure, hilar and intrahepatic cholangiocarcinoma, and unresectable liver metastases of colorectal cancer., Conclusions: We present the main recommendations issued for each topic, together with their core supporting evidence. These recommendations may allow for expanding criteria for LT homogenously in Spain and may provide a guidance to other countries/institutions facing a similar scenario., Competing Interests: The authors of the present manuscript have no conflict of interest to disclose as described by the Transplantation Journal., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background & Aims: The incidence and outcomes of coronavirus disease 2019 (COVID-19) in immunocompromised patients are a matter of debate., Methods: We performed a prospective nationwide study including a consecutive cohort of liver transplant patients with COVID-19 recruited during the Spanish outbreak from 28 February to 7 April, 2020. The primary outcome was severe COVID-19, defined as the need for mechanical ventilation, intensive care, and/or death. Age- and gender-standardised incidence and mortality ratios (SIR and SMR) were calculated using data from the Ministry of Health and the Spanish liver transplant registry. Independent predictors of severe COVID-19 among hospitalised patients were analysed using multivariate Cox regression., Results: A total of 111 liver transplant patients were diagnosed with COVID-19 (SIR = 191.2 [95% CI 190.3-192.2]). The epidemiological curve and geographic distribution overlapped widely between the liver transplant and general populations. After a median follow-up of 23 days, 96 patients (86.5%) were admitted to hospital and 22 patients (19.8%) required respiratory support. A total of 12 patients were admitted to the ICU (10.8%). The mortality rate was 18%, which was lower than in the matched general population (SMR = 95.5 [95% CI 94.2-96.8]). Overall, 35 patients (31.5%) met criteria of severe COVID-19. Baseline immunosuppression containing mycophenolate was an independent predictor of severe COVID-19 (relative risk = 3.94; 95% CI 1.59-9.74; p = 0.003), particularly at doses higher than 1,000 mg/day (p = 0.003). This deleterious effect was not observed with calcineurin inhibitors or everolimus and complete immunosuppression withdrawal showed no benefit., Conclusions: Being chronically immunosuppressed, liver transplant patients have an increased risk of acquiring COVID-19 but their mortality rates are lower than the matched general population. Upon hospital admission, mycophenolate dose reduction or withdrawal could help in preventing severe COVID-19. However, complete immunosuppression withdrawal should be discouraged., Lay Summary: In liver transplant patients, chronic immunosuppression increases the risk of acquiring COVID-19 but it could reduce disease severity. Complete immunosuppression withdrawal may not be justified. However, mycophenolate withdrawal or temporary conversion to calcineurin inhibitors or everolimus until disease resolution could be beneficial in hospitalised patients., Competing Interests: Conflicts of interest JC has received lecture fees from Chiesi, Astellas, and Novartis and is an advisory to Chiesi. MR-P has received lecture fees from Astellas, Novartis, and Intercept Pharma. MS has received lecture fees from Astellas, Novartis, and Chiesi and is an advisory to Jazz and Novartis. MG has received speaker fees from and/or acted as advisor for Astellas, Novartis, Chiesi, Baxter, and Medtronic. MN has received lecture fees from Astellas Pharma. MI has received lecture fees from BMS. CV has received lecture fees from Novartis, Abbie, and Gilead. AC has received lecture fees from Astellas Pharma. GB-F has received lecture fees from Bayer and Astellas. JLM has received lecture fees from Bayer and Gilead. JP has received lecture fees by Astellas, Chiesi, and Gilead. AA-M, AM-S, JG, JN, JB-S, AC, LL, AC, AF-Y, CL, IF, CF, LC, SP, PR, MG-D, RG-G, LH, FN, AO, JA, EF, FG-P, ST and GDR have no conflict of interest to disclose regarding this manuscript. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The Sustained Alcohol use post-Liver Transplant (SALT) and the High-Risk Alcohol Relapse (HRAR) scores were developed to predict a return to alcohol use after a liver transplant (LT) for alcohol-associated liver disease. A retrospective analysis of deceased donor LT from October 2018 to April 2022 was performed. All patients underwent careful pre-LT psychosocial evaluation. Data on alcohol use, substance abuse, prior rehabilitation, and legal issues were collected. After LT, all were encouraged to participate in rehabilitation programs and underwent interval phosphatidylethanol testing. Patients with alcohol-associated liver disease were stratified by < or > 6 months of sobriety before listing. Those with <6 months were further stratified as acute alcoholic hepatitis (AH) by NIAAA criteria and non-AH. The primary outcome was the utility of the SALT (<5 vs. ≥5) and HRAR (<3 vs. ≥3) scores to predict a return to alcohol use (+phosphatidylethanol) within 1 year after LT. Of the 365 LT, 86 had > 6 months of sobriety, and 85 had <6 months of sobriety; 41 with AH and 44 non-AH. In those with AH, the mean time of abstinence to LT was 58 days, and 71% failed prior rehabilitation. Following LT, the return to drinking was similar in the AH (24%) compared to <6-month non-AH (15%) and >6-month alcohol-associated liver disease (22%). Only 4% had returned to heavy drinking. The accuracy of both the SALT and HRAR scores to predict a return to alcohol was low (accuracy 61%-63%) with poor sensitivity (46% and 37%), specificity (67%-68%), positive predictive value (22%-26%) with moderate negative predictive value (81%-83%), respectively with higher negative predictive values (95%) in predicting a return to heavy drinking. Both SALT and HRAR scores had good negative predictive value in identifying patients at low risk for recidivism., (Copyright © 2024 American Association for the Study of Liver Diseases.)

In a setting characterized by a growing prevalence of patients with alcohol-associated and metabolic dysfunction-associated steatotic liver diseases, coupled with an aging patient demographic, the incidence of cardiac comorbidities in liver transplant candidates is on the rise. These comorbidities not only pose barriers to transplant eligibility but also impact the intraoperative course and affect posttransplant outcomes. As such, there is a significant need to optimize the clinical management of these cardiac comorbidities. However, there is a scarcity of evidence regarding the best practices for managing cardiac comorbidities such as coronary and valvular heart diseases, arrhythmia, and cardiomyopathy in this population, both before and during transplant surgery. These conditions necessitate a coordinated and multidisciplinary approach to care. In this manuscript, we conduct a comprehensive review of the most recent evidence pertaining to the preoperative and intraoperative management of these cardiac comorbidities in liver transplant candidates. Our aim is to provide recommendations that improve and standardize their clinical care., (Copyright © 2024 American Association for the Study of Liver Diseases.)

MicroRNAs (miRNAs) are small noncoding RNAs that can be detected in plasma and whose expression is associated with pathological processes. The role of miRNAs in the noninvasive diagnosis of T cell-mediated rejection (TCMR) after liver transplantation (LT) is unclear. Thus, we aimed to assess the effectiveness of a panel of 4 miRNAs (155-5p, 122-5p, 181a-5p, and 148-3p) in diagnosing TCMR in LT recipients with graft dysfunction (GD), and we compared its accuracy with previously published tests for diagnosing TCMR based on routine laboratory parameters. From a prospective cohort of 145 patients followed during the first year after transplant, 49 developed GD and underwent a liver biopsy and plasma collection for miRNA analysis using quantitative real-time polymerase chain reaction. Patients with GD due to TCMR (n = 21) exhibited significantly higher (P < 0.001) expression of miRNA 155-5p (2.05 versus 0.07), 122-5p (19.36 versus 1.66), and 181a-5p (1.33 versus 0.37) compared with those with GD from other causes (n = 28). The area under the receiver operating characteristic curve of miRNAs 155-5p, 122-5p, and 181a-5p for the diagnosis of TCMR was 0.87, 0.91, and 0.89, respectively, significantly higher than those of the other noninvasive tests (P < 0.001). Furthermore, miRNA 155-5p identified all patients who presented TCMR during the first 2 weeks after transplant. miRNA plasmatic expression differentiates TCMR from other causes of GD in patients who have undergone LT and may be a useful tool in clinical practice., (Copyright © 2020 American Association for the Study of Liver Diseases.)

Livers from donation after circulatory death (DCD) donors are an increasingly more common source of organs for transplantation. While there are few high-level studies in the field of DCD liver transplantation, clinical practice has undergone progressive changes during the past decade, in particular due to mounting use of postmortem normothermic regional perfusion (NRP). In Spain, uncontrolled DCD has been performed since the late 1980s/early 1990s, while controlled DCD was implemented nationally in 2012. Since 2012, the rise in DCD liver transplant activity in Spain has been considerable, and the great majority of DCD livers transplanted in Spain today are recovered with NRP. A panel of the Spanish Liver Transplantation Society was convened in 2018 to evaluate current evidence and accumulated experience in DCD liver transplantation, in particular addressing issues related to DCD liver evaluation, acceptance criteria, and recovery as well as recipient selection and postoperative management. This panel has created a series of consensus statements for the standard of practice in Spain and has published these statements with the hope they might help guide other groups interested in implementing new forms of DCD liver transplantation and/or introducing NRP into their clinical practices., (© 2020 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

Recipients of simultaneous liver-kidney transplantations (SLKTs) have a lower risk of rejection compared with recipients of kidney transplants alone. However, there is disagreement about the impact of pretransplant anti-human leukocyte antigen sensitization on patient and kidney graft survival in the long term. The aim of the study was to evaluate the impact of the recipient immunological risk and comorbidities in renal graft outcomes on SLKT. We reviewed the SLKTs performed in our center from May 1993 until September 2017. Patient and graft survival were analyzed according to the immunological risk, comorbidities, liver and kidney rejection episodes, immunosuppression, and infections. A total of 20 recipients of SLKT were considered in the high immunological risk (HIR) group, and 68 recipients were included in the low immunological risk (LIR) control group. The prevalence of hepatitis C virus infection, second renal transplant, and time on dialysis prior to transplantation were significantly higher in the HIR group. The incidence of acute kidney rejection was higher in the HIR group (P<0.01). However, death-censored kidney graft survival as well as the estimated glomerular filtration rate at follow-up were not different between the 2 groups. Comorbidities, but not the immunological risk, impact negatively on patient survival. Despite the higher incidence of rejection in the HIR SLKT group, longterm renal function and graft survival were similar to the LIR group., (Copyright © 2020 by the American Association for the Study of Liver Diseases.)

Whilst prophylaxis of hepatitis B is universally accepted after liver transplantation (LT), national recommendations for the prophylaxis and treatment of hepatitis B virus (HBV) infection after LT are lacking in Spain. The aim of the VII consensus meeting organised by the Spanish Society of Liver Transplantation (SETH) was to set recommendations on the prophylaxis and treatment of hepatitis B after LT. The scientific evidence and strength of recommendations was evaluated by using the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) system. This document describes the recommendations and their level of evidence for: the definition and risk factors for hepatitis B recurrence after LT, monitoring and prophylaxis of hepatitis B recurrence at different periods after LT, treatment of hepatitis B before and after LT, and the prophylaxis of HBV infection by the recipients of LT with hepatitis B core antigen positive donors., (Copyright © 2020 Elsevier España, S.L.U. All rights reserved.)

Background: Information on the risk factors, particularly kidney function, and impact of long-term cardiovascular events (CVE) after liver transplantation (LT) remains scarce., Methods: This is a retrospective, single-center study that included consecutive LT recipients between 2007 and 2017. The incidence of CVE, their risk factors, and their impact on patient survival were investigated., Results: We included 627 LT recipients. The incidence of CVE was 8% and 20% at 12 and 60 months after LT, respectively. The independent risk factors of long-term (beyond 12 mo) CVE were age at LT (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.01-1.07), male gender (HR, 2.48; 95% CI, 1.21-5.05), history of pre-LT cardiovascular disease (HR, 2.19; 95% CI, 1.2-3.98), and immunosuppression with cyclosporine A (HR, 1.93; 95% CI, 1.14-3.3). In patients with pre-LT cardiovascular disease, creatinine levels 12 months after LT significantly impacted the risk of long-term CVE. Long-term CVE (HR, 2.12; 95% CI, 1.24-3.61), hepatitis C as the etiology of liver disease (HR, 2.18; 95% CI, 1.29-3.67), cytomegalovirus infection (HR, 1.89; 95% CI, 1.08-3.3), and donor age (HR, 1.02; 95% CI, 1.01-1.04) were independent factors associated with post-LT patient death., Conclusions: Age, male gender, cardiovascular disease before LT, and cyclosporine A were associated with the risk of long-term CVE. The impact of serum creatinine was restricted to patients with pre-LT cardiovascular disease. In these patients, preservation of kidney function early after LT may lessen the incidence of CVE, which are an independent predictor of post-LT death.

Despite unique immunoregulatory properties pointing toward tolerance, the liver allograft can be negatively impacted by humoral alloreactivity, with immediate as well as long-term harmful consequences. With regard to the unmet need of long-term outcomes improvement after liver transplantation, donor-specific antibodies have recently been the matter of intense study in this context. We review here recent advances regarding the understanding of the impact of preformed as well as de novo anti-human leukocyte antigen donor-specific antibodies in liver transplantation and discuss potential strategies to overcome this problem., (Copyright © 2019 Elsevier España, S.L.U. All rights reserved.)

Background: Alcohol-associated hepatitis (AH) is associated with significant mortality. Model for End-Stage Liver Disease (MELD) score is used to predict short-term mortality and aid in treatment decisions. MELD is frequently updated in the course of AH. However, once the most updated MELD is known, it is uncertain if previous ones still have prognostic value, which might be relevant for transplant allocation and trial design. We aimed to investigate the predictive performance of updated MELDs in a prospectively collected cohort of patients with AH by the InTeam consortium., Methods: Three hundred seven patients (with 859 MELD values within 60 d of admission) fulfilled the inclusion criteria. The main endpoint was time to death or transplant up to 90 days. We used a joint model approach to assess the predictive value of updated MELDs., Results: Updated MELD measurements had a strong prognostic value for death/transplant (HR: 1.20, 95% CI: 1.14-1.27) (p < 0.0001). Previous MELD values did not add predictive value to the most current MELD. We also showed that MELD at day 28 (MELD28) had a significant predictive value for subsequent mortality/transplant in a landmark analysis (HR: 1.18, 95% CI: 1.12-1.23). We show that the use of an ordinal scale including death, transplant, and MELD28 as a trial outcome could substantially reduce the sample size required to demonstrate short-term benefit of an intervention., Conclusion: We show that updated MELDs during the trajectory of AH predict subsequent mortality or the need for transplant. MELD28 inclusion in an ordinal outcome (together with death or transplant) could increase the efficiency of randomized controlled trials., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Purpose: Hepatic veno-occlusive disease (HVOD) after liver transplantation (LT) is almost always a fatal complication. We assessed the outcomes of HVOD in a single institute and analyzed a literature-based cohort., Methods: We reviewed the medical records of recipients of LT performed between 1995 and 2020 at our institute and the literature on HVOD after LT. We then analyzed the clinical features based on a "pooled" cohort of cases identified in our institute and reported in the literature., Results: HVOD was diagnosed in 3 of 331 LT recipients, all of whom died in hospital, on days 164, 12, and 13, respectively. Our comprehensive review of the literature, as well as our cases, identified eight cases of HVOD that developed within 14 days after LT (early-onset type). Early-onset HVOD had a significantly worse prognosis than HVOD that developed beyond 2 weeks after LT (non-early-onset type), which was identified in 22 cases (25.0% vs. 86.1% of the 3-month graft survival rate). The most common causes of early-onset and non-early-onset types were acute cellular rejection (50%) and drug-induced disease (50%), respectively., Conclusion: Early-onset HVOD developing within 14 days after LT has a poor prognosis., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Alcohol liver disease (ALD) may coexist with hepatitis C (HCV) in many transplant recipients (alcoholic cirrhosis with hepatitis C [AHC]). Our objective was to determine whether there were differences in postliver transplantation outcomes of patients with AHC when compared with those with alcoholic cirrhosis (AC) and/or alcoholic hepatitis (AH)., Methods: Using UNOS explant data sets (2016-2020), the survival probabilities of AC, AH, and AHC were compared by Kaplan-Meier survival analysis. Cox proportional-hazard regression analysis was used to determine outcomes after adjusting for disease confounders. The outcomes were also compared with predirect antiviral agent (DAA) period., Results: During study period, 8369 biopsy-proven ALD liver transplant recipients were identified. Of those, 647 had AHC (HCV + alcohol), 353 had AH, and 7369 had AC. MELD-Na score (28.7 ± 9.5 versus 23.8 ± 10.7; P  < 0.001) and presence of ACLF-3 (19% versus 11%; P  < 0.001) were higher in AC + AH as compared with AHC. AHC and AC+AH has similar adjusted mortality at 1-y, but 3-y (hazard ratios, 1.76; 95% confidence intervals, 1.32-2.35; P  < 0.0001) and 5-y (hazard ratios, 1.64; 95% confidence intervals, 1.24-2.15; P  = 0.0004) mortality rates were higher in AHC. Survival improved in the DAA era (2016-2020) compared with 2009 to 2013 in AHC, but remained worse in AHC group versus AC and/or AH. Malignancy-related mortality was higher in AHC (15% versus 9.3% in AC) in the DAA era., Conclusions: AHC was associated with lower 3- and 5-y post-LT survival as compared with ALD without HCV and the worse outcomes in AHC group continued in the DAA era., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The selection of liver transplantation (LT) candidates with alcohol-use disorder (AUD) is influenced by the risk of alcohol relapse (AR) after LT. We aimed to investigate the risk factors of AR after LT and its impact on graft and recipient outcomes. A retrospective study was conducted that included all consecutive patients with AUD undergoing LT from January 2004 to April 2016 (n = 309), excluding patients with alcoholic hepatitis. Odds ratios (ORs) and 95% confidence intervals (CIs) for AR were analyzed by multinomial logistic regression. Cox regression with time-dependent covariates was used to analyze patient survival and graft cirrhosis. There were 70 (23%) patients who presented AR (median follow-up, 68 months), most of them (n = 44, 63%) presenting heavy AR. The probability of heavy AR was 2.3%, 7.5%, 12%, and 29% at 1, 3, 5, and 10 years after LT, respectively. The independent risk factors for heavy AR included a High-Risk Alcoholism Relapse (HRAR) score ≥3 (OR, 2.39; 95% CI, 1.02-5.56; P = 0.04) and the duration of abstinence (months) before LT (OR, 0.81; 95% CI, 0.66-0.98; P = 0.03). In recipients with <6 months of abstinence before LT, the probability of heavy AR after LT was higher in patients with an HRAR score ≥3 than in those with an HRAR score <3 (20%, 36.7%, and 47% versus 6.8%, 12.4%, and 27% at 1, 3, and 5 years, respectively; log-rank 0.013). The risk of graft cirrhosis was increased in patients with heavy AR (hazard ratio, 3.44; 95% CI, 1.58-7.57; P = 0.002) compared with nonrelapsers, with no differences in patient survival. In conclusion, the HRAR score is helpful in identifying the risk of harmful AR after LT in candidates with <6 months of alcohol abstinence without alcoholic hepatitis. These patients could benefit from a longterm integrative patient-centered approach after LT until lifestyle changes are implemented., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

The development of noninvasive biomarkers that reflect the state of immunosuppression (IS) remains an unmet need in liver transplantation (LT). Torque Teno virus (TTV) is a highly prevalent, nonpathogenic DNA virus whose plasma levels may be associated with the immune status of the host. The aim of this study was to assess the role of TTV as a biomarker of IS in LT recipients. TTV DNA in plasma was quantified by real-time polymerase chain reaction at different time points during the first year after transplant in a prospectively followed cohort of 63 de novo LT recipients, and any correlation between TTV DNA and biopsy-proven acute cellular rejection (ACR) and opportunistic infections was then evaluated. In addition, TTV DNA was studied in 10 longterm LT recipients in monotherapy with tacrolimus, 10 tolerant recipients, and 10 healthy controls. TTV was detected in the plasma of all patients. Among the 63 LT recipients, 20 episodes of ACR were diagnosed, and there were 28 opportunistic infections, 26 of them being cytomegalovirus (CMV) infections. TTV viremia was significantly lower during ACR (4.41 versus 5.95 log 10 copies/mL; P = 0.002) and significantly higher during CMV infections (5.79 versus 6.59 log 10 copies/mL; P = 0.009). The area under the receiver operating characteristic curve of TTV viral load for the diagnosis of moderate ACR was 0.869, with a sensitivity and negative predictive value of 100%, respectively, for a cutoff point of 4.75 log 10 copies/mL. There were no statistically significant differences in TTV DNA in either longterm or tolerant patients and healthy controls. In conclusion, plasma TTV DNA levels are associated with immune-related events after LT and could constitute a potential biomarker of the state of IS during the first months after transplant., (Copyright © 2018 by the American Association for the Study of Liver Diseases.)

Background & Aims: Patients with decompensated cirrhosis on the waiting list for liver transplantation (LT) commonly develop complications that may preclude them from reaching LT. Circulatory dysfunction leading to effective arterial hypovolemia and activation of vasoconstrictor systems is a key factor in the pathophysiology of complications of cirrhosis. The aim of this study was to investigate whether treatment with midodrine, an alpha-adrenergic vasoconstrictor, together with intravenous albumin improves circulatory dysfunction and prevents complications of cirrhosis in patients awaiting LT., Methods: A multicenter, randomized, double-blind, placebo-controlled trial (NCT00839358) was conducted, including 196 consecutive patients with cirrhosis and ascites awaiting LT. Patients were randomly assigned to receive midodrine (15-30 mg/day) and albumin (40 g/15 days) or matching placebos for one year, until LT or drop-off from inclusion on the waiting list. The primary endpoint was incidence of any complication (renal failure, hyponatremia, infections, hepatic encephalopathy or gastrointestinal bleeding). Secondary endpoints were mortality, activity of endogenous vasoconstrictor systems and plasma cytokine levels., Results: There were no significant differences between both groups in the probability of developing complications of cirrhosis during follow-up (p = 0.402) or one-year mortality (p = 0.527). Treatment with midodrine and albumin was associated with a slight but significant decrease in plasma renin activity and aldosterone compared to placebo (renin -4.3 vs. 0.1 ng/ml.h, p < 0.001; aldosterone -38 vs. 6 ng/dl, p = 0.02, at week 48 vs. baseline). Plasma norepinephrine only decreased slightly at week 4. Neither arterial pressure nor plasma cytokine levels changed significantly., Conclusions: In patients with cirrhosis awaiting LT, treatment with midodrine and albumin, at the doses used in this study, slightly suppressed the activity of vasoconstrictor systems, but did not prevent complications of cirrhosis or improve survival., Lay Summary: Patients with cirrhosis who are on the liver transplant waiting list often develop complications which prevent them from receiving a transplant. Circulatory dysfunction is a key factor behind a number of complications. This study was aimed at investigating whether treating patients with midodrine (a vasoconstrictor) and albumin would improve circulatory dysfunction and prevent complications. This combined treatment, at least at the doses administered in this study, did not prevent the complications of cirrhosis or improve the survival of these patients., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: The selection of liver transplant (LT) candidates with alcohol-related liver disease (ALD) is influenced by the risk of alcohol relapse (AR), yet the ability to predict AR is limited. We evaluate psychosocial factors associated with post-LT AR and compare the performance of high-risk alcoholism risk (HRAR), sustained alcohol use post-LT (SALT), and the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) scores in predicting relapse., Methods: A retrospective analysis of ALD patients undergoing LT from 2015 to 2021 at a single US transplant center was performed. Risk factors associated with post-LT AR were evaluated and test characteristics of 3 prediction models were compared., Results: Of 219 ALD LT recipients, 23 (11%) had AR during a median study follow-up of 37.5 mo. On multivariate analysis, comorbid psychiatric illness (odds ratio 5.22) and continued alcohol use after advice from a health care provider (odds ratio 3.8) were found to be significantly associated with post-LT AR. On sensitivity analysis, SIPAT of 30 was optimal on discriminating between ALD LT recipients with and without post-LT AR. SIPAT outperformed both the HRAR and SALT scores (c-statistic 0.67 versus 0.59 and 0.62, respectively) in identifying post-LT AR. However, all scores had poor positive predictive value (<25%)., Conclusions: AR after LT is associated with comorbid psychiatric illness and lack of heeding health care provider advice to abstain from alcohol. Although SIPAT outperformed the HRAR and SALT scores in predicting AR, all are poor predictors. The current tools to predict post-LT AR should not be used to exclude LT candidacy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The goal of the Spanish Liver Transplantation Society (La Sociedad Española de Trasplante Hepático) is to promote and create consensus documents about current topics in liver transplantation with a multidisciplinary approach. To this end, on October 20, 2016, the 6th Consensus Document Meeting was held, with the participation of experts from the 24 authorized Spanish liver transplantation programs. This Edition discusses the following subjects, whose summary is offered below: 1) limits of simultaneous liver-kidney transplantation; 2) limits of elective liver re-transplantation; and 3) liver transplantation after resection and hepatocellular carcinoma with factors for a poor prognosis. The consensus conclusions for each of these topics is provided below., (Copyright © 2018. Publicado por Elsevier España, S.L.U.)

Thromboprophylaxis is not well defined after liver transplantation (LT). The aim of this study was to evaluate the incidence of splanchnic vein thrombosis (SVT) and nonsplanchnic vein thrombosis (NSVT) after LT. Liver transplantations performed between 2009 and 2013 in our institution were reviewed. Demographic, intraoperative, and postoperative data were recorded. Low-molecular-weight heparin was only administered postoperatively if intraoperative thrombectomy was performed or in patients preoperatively anticoagulated. Of a total of 328 patients, 72% were male with a median age of 56 years, score of model for end-stage liver disease 18 (11-23), and 88% had liver cirrhosis. The incidence of postoperative venous thrombotic events was 4.6%: 8 (2.4%) patients had SVT and 7 (2.1%) patients had NSVT. After logistic regression analysis, intraoperative thrombectomy and Child A classification emerged as risk factors for SVT (odds ratio [OR]: 77, 95% confidence interval [95% CI]: 14-421) and NSVT (OR: 20, 95% CI: 3-170), respectively. The incidence of SVT in patients who undergo intraoperative thrombectomy was 33%, whereas the incidence of NSVT in patients grouped as Child A was 7.5%. Our results suggest that thromboprophylaxis should be considered after LT in patients with cirrhosis grouped as Child A and in patients who undergo intraoperative thrombectomy.

A subset of patients with hepatocellular carcinoma (HCC) beyond Milan criteria might obtain acceptable survival outcomes after liver transplantation. Living donor liver transplantation (LDLT) has emerged as a feasible alternative to overcome the paucity of donors. In 2001, we started a protocol for LDLT in Child A-B patients with HCC fulfilling a set of criteria-the Barcelona Clinic Liver Cancer (BCLC) expanded criteria-that expanded the conventional indications of transplantation: 1 tumor ≤ 7 cm, 5 tumors ≤ 3 cm, and 3 tumors ≤ 5 cm without macrovascular invasion or downstaging to Milan after locoregional therapies. We present a prospective cohort of 22 patients with BCLC extended indications based on size/number (n = 17) or downstaging (n = 5) treated with LDLT between 2001 and 2014. Characteristics of the patients were as follows: median age, 57 years old; males/female, n = 20/2; Child-Pugh A/B, n = 16/6; and alpha fetoprotein < 100 ng/mL, n = 21. Twelve patients received neoadjuvant locoregional therapies. At the time of transplantation, 12 patients had HCC staging beyond Milan criteria and 10 within. Pathological reports showed that 50% exceeded BCLC expanded criteria. Perioperative mortality was 0%. After a median follow-up of 81 months, the 1-, 3-, 5-, and 10-year survival was 95.5%, 86.4%, 80.2%, and 66.8%, respectively. Overall, 7 patients recurred (range, 9-108 months), and the 5-year and 10-year actuarial recurrence rates were 23.8% and 44.4%, respectively. In conclusion, a proper selection of candidates for extended indications of LDLT for HCC patients provide survival outcomes comparable to those obtained within the Milan criteria, but these results need confirmation. Liver Transplantation 24 369-379 2018 AASLD., (© 2017 by the American Association for the Study of Liver Diseases.)

Mannose-binding lectin (MBL) is synthesized by the liver and binds to microbes. MBL2 gene polymorphisms produce intermediate/low/null or normal MBL serum levels (MBL-deficient or MBL-sufficient phenotypes, respectively). We aimed to evaluate the incidence and severity of infection, rejection, and survival within 1 year after liver transplantation (LT) according to donor and recipient MBL2 gene polymorphisms. A repeated-event analysis for infection episodes (negative binomial regression, Andersen-Gill model) was performed in 240 LTs. Four hundred twenty-eight infectious episodes (310 bacterial, 15 fungal, 65 cytomegalovirus [CMV]-related, and 38 viral non-CMV-related episodes) and 48 rejection episodes were recorded. The main bacterial infections were urinary (n = 82, 26%) and pneumonia (n = 69, 22%). LT recipients of MBL-deficient livers had a higher risk of bacterial infection (incidence rate ratio [IRR] 1.48 [95% confidence interval 1.04-2.09], p = 0.028), pneumonia (IRR 2.4 [95% confidence interval 1.33-4.33], p = 0.013), and septic shock (IRR 5.62 [95% confidence interval 1.92-16.4], p = 0.002) compared with recipients of MBL-deficient livers. The 1-year bacterial infection-related mortality was higher in recipients of MBL-deficient versus MBL-sufficient livers (65.8% vs. 56.1%, respectively; p = 0.0097). The incidence of rejection, viral, or fungal infection was similar in both groups. Recipient MBL2 genotype did not significantly increase the risk of bacterial infection. LT recipients of MBL-deficient livers have a higher risk of bacterial infection, pneumonia, septic shock, and 1-year bacterial infection-related mortality after LT., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background & Aims: Antiviral therapy for the treatment of hepatitis C (HCV) infection has proved to be safe and efficacious in patients with cirrhosis awaiting liver transplantation (LT). However, the information regarding the clinical impact of viral eradication in patients on the waiting list is still limited. The aim of the study was to investigate the probability of delisting in patients who underwent antiviral therapy, and the clinical outcomes of these delisted patients., Methods: Observational, multicenter and retrospective analysis was carried out on prospectively collected data from patients positive for HCV, treated with an interferon-free regimen, while awaiting LT in 18 hospitals in Spain., Results: In total, 238 patients were enrolled in the study. The indication for LT was decompensated cirrhosis (with or without hepatocellular carcinoma [HCC]) in 171 (72%) patients, and HCC in 67 (28%) patients. Sustained virologic response (SVR) rate was significantly higher in patients with compensated cirrhosis and HCC (92% vs. 83% in patients with decompensated cirrhosis with or without HCC, p=0.042). Among 122 patients with decompensated cirrhosis without HCC, 29 (24%) were delisted due to improvement. No patient with baseline MELD score >20 was delisted. After delisting (median follow-up of 88weeks), three patients had clinical decompensations and three had de novo HCC. Only two of the patients with HCC had to be re-admitted onto the waiting list. The remaining 23 patients remained stable, with no indication for LT., Conclusions: Antiviral therapy is safe and efficacious in patients awaiting LT. A quarter of patients with decompensated cirrhosis can be delisted asa result of clinical improvement, which appears to be remain stable in most patients. Thus, delisting is a safe strategy that could spare organs and benefit other patients with a more urgent need., Lay Summary: Antiviral therapy in patients awaiting liver transplantation is safe and efficacious. Viral eradication allows removal from the waiting list of a quarter of treated patients. Delisting because of clinical improvement is a safe strategy that can spare organs for patients in urgent need., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)