Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma: a multicenter cohort study in China.

OBJECTIVE: Sex-specific differences are observed in various liver diseases, but the influence of sex on the outcomes of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains to be determined. This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC. METHODS: Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed. The associations between donor, recipient, or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching (PSM). The survival associated with different sex-based donor-recipient transplant patterns was further studied. RESULTS: Among 3,769 patients enrolled in this study, the 1-, 3-, and 5-year overall survival (OS) rates of patients with HCC after LT were 96.1%, 86.4%, and 78.5%, respectively, in female recipients, and 95.8%, 79.0%, and 70.7%, respectively, in male recipients after PSM (P = 0.009). However, the OS was comparable between recipients with female donors and male donors. Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival (HR = 1.381, P = 0.046). Among the donor-recipient transplant patterns, the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival (P < 0.05). CONCLUSIONS: Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients, and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival. Livers from male donors may provide the most benefit to female recipients. Our results indicate that sex should be considered as a critical factor in organ allocation.

Impact of preoperative infection on the outcomes of liver transplant recipients: a national propensity score-matched retrospective cohort study in China.

BACKGROUND: Impact of preoperative infection on liver transplantation (LT) needs further investigation. MATERIALS AND METHODS: From 1 January 2015 to 31 December 2022, 24 122 eligible patients receiving LT were enrolled from the China Liver Transplant Registry database. The outcomes of LT were compared after using the propensity score-matched analysis. RESULTS: Compared to the noninfection group, patients in the infection group were more likely to have postoperative effusion, infection, abdominal bleeding, and biliary complications (all P <0.01), and they had shorter 30-day, 90-day survival, and overall survival (all P <0.01). Cox proportional hazards regression analysis revealed that MELD score and cold ischemia time were risk factors for the overall survival in the infection group (both P <0.05). Besides, compared to the nonpulmonary group, patients in the pulmonary group were more likely to have postoperative effusion and infection (both P <0.0001), and less likely to have postoperative abscess and early allograft dysfunction (both P <0.05). Patients in the nonabdominal group also had a higher proportion of postoperative infection than those in the abdominal group ( P <0.05). Furthermore, compared to the number=1 group, patients in the number ≥2 group were more prone to postoperative effusion and infection (both P <0.01), and they also had shorter 30-day and 90-day survival (both P <0.05). CONCLUSION: Preoperative infection can result in a higher incidence of early postoperative complications and shorter survival in liver transplant recipients. The types and number of infection sites will also influence the prognosis of liver transplant recipients.

Comparisons between White and Black Patients Hospitalized with Postliver Transplant Complications/Failure.

OBJECTIVES: The impact of race on patients presenting to North American hospitals with postliver transplant complications/failure (PLTCF) has not been studied fully. We compared in-hospital mortality and resource utilization outcomes between White and Black patients hospitalized with PLTCF. METHODS: This was a retrospective cohort study that evaluated the years 2016 and 2017 from the National Inpatient Sample. Regression analysis was used to determine in-hospital mortality and resource utilization. RESULTS: There were 10,805 hospitalizations for adults with liver transplants who presented with PLTCF. White and Black patients with PLTCF made up 7925 (73.3%) hospitalizations from this population. Among this group, 6480 were White (81.7%) and 1445 were Black (18.2%). Blacks were younger than Whites (mean age ± standard error of the mean: 46.8 ± 1.1 vs 53.6 ± 0.39 years, P < 0.01). Blacks were more likely to be female (53.9% vs 37.4%, P < 0.01). Charlson Comorbidity Index scores were not significantly different (scores ≥3: 46.7% vs 44.2%, P = 0.83). Blacks had significantly higher odds for in-hospital mortality (adjusted odds ratio 2.9, confidence interval [CI] 1.4-6.1; P < 0.01). Hospital charges were higher for Blacks compared with Whites (adjusted mean difference $48,432; 95% CI $2708-$94,157, P = 0.03). Blacks had significantly longer lengths of hospital stays (adjusted mean difference 3.1 days, 95% CI 1.1-5.1, P < 0.01). CONCLUSIONS: Compared with White patients hospitalized for PLTCF, Black patients had higher in-hospital mortality and resource use. Investigation into causes leading to this health disparity is needed to improve in-hospital outcomes.

Combined heart and liver transplantation: an updated systematic review.

INTRODUCTION: Combined heart and liver transplantation (CHLT) is one of the most complex procedures of surgery that has been implemented in the last 35 years. The aim of our meta-analysis was to investigate the safety and efficacy of CHLT. MATERIALS: The meta-analysis was designed according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) and AMSTAR (A MeaSurement Tool to Assess systematic Reviews) recommendations. A literature search was conducted up to April 2020 using the MEDLINE,® SCOPUS,® ClinicalTrials.gov, Embase™, Cochrane Central Register of Controlled Trials and Google Scholar™ databases. RESULTS: Our meta-analysis included 16 studies with 860 patients. The mortality rate following CHLT was 14.1%. One and five-year survival rates were 85.3% and 71.4% while the heart and liver rejection rates were 6.1% and 9.1% respectively. The hospital stay was 25.8 days and the intensive care unit stay was 9.9 days. Pooled values were also calculated for cardiopulmonary bypass duration, units of transfused red blood cells and fresh frozen plasma, postoperative infection rate, mechanical ventilation rate and follow-up duration. CONCLUSIONS: Despite its complexity, CHLT is a safe and effective procedure for the management of lethal diseases that lead to progressive heart and/or liver failure. Nevertheless, there must be strict adherence to the indications for surgery, and future studies should compare CHLT with isolated cardiac and hepatic transplantations.

Trends in Survival for Pediatric Transplantation.

OBJECTIVES: Progress in pediatric transplantation measured in the context of waitlist and posttransplant survival is well documented but falls short of providing a complete perspective for children and their families. An intent-to-treat analysis, in which we measure survival from listing to death regardless of whether a transplant is received, provides a more comprehensive perspective through which progress can be examined. METHODS: Univariable and multivariable Cox regression was used to analyze factors impacting intent-to-treat survival in 12 984 children listed for heart transplant, 17 519 children listed for liver transplant, and 16 699 children listed for kidney transplant. The Kaplan-Meier method and log-rank test were used to assess change in waitlist, posttransplant, and intent-to-treat survival. Wait times and transplant rates were compared by using χ2 tests. RESULTS: Intent-to-treat survival steadily improved from 1987 to 2017 in children listed for heart (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.96-0.97), liver (HR 0.95, 95% CI 0.94-0.97), and kidney (HR 0.97, 95% CI 0.95-0.99) transplant. Waitlist and posttransplant survival also improved steadily for all 3 organs. For heart transplant, the percentage of patients transplanted within 1 year significantly increased from 1987 to 2017 (60.8% vs 68.7%); however, no significant increase was observed in liver (68.9% vs 72.5%) or kidney (59.2% vs 62.7%) transplant. CONCLUSIONS: Intent-to-treat survival, which is more representative of the patient perspective than individual metrics alone, steadily improved for heart, liver, and kidney transplant over the study period. Further efforts to maximize the donor pool, improve posttransplant outcomes, and optimize patient care while on the waitlist may contribute to future progress.

Three decades' analysis of pediatric liver transplantation outcomes reveals limited long-term improvements.

BACKGROUND: The aim of this study was to assess improvements in long-term survival of pediatric patients after liver transplantation by analyzing outcomes in transplant recipients who survived beyond 1 year after transplantation. There has been a marked increase in the 1-year survival of pediatric patients, from 78% in transplant recipients between 1987 and 1990 to 95% in transplant recipients between 2011 and 2017. The long-term outcomes have not seen a similar trend, creating a disparity that warrants analysis. METHODS: We analyzed 13 753 pediatric patients who survived for 1 year after receiving orthotopic liver transplantation between 1987 and 2017. The study period was divided into six eras. Outcomes were analyzed using the Kaplan-Meier method for time-to-event analysis, and multivariable Cox regression. RESULTS: There were no significant gains in long-term outcomes among 1-year survivors over the past three decades. Log-rank tests for equality of survivor functions between each era and 1987-1990 were not statistically significant. Cause of death analysis revealed that although infections caused 20.6% of deaths in patients transplanted between 1987 and 1990, this number dropped to 5.6% in those transplanted between 2011 and 2017 (p = .01). Malignancy caused 10.6% of deaths in 1987-1990 but caused 22.2% of the deaths in 2011-2017 (p = .04). CONCLUSION: Despite the gratifying gains in short-term survival of pediatric patients, 1-year survivors have no significant improvements in long-term survival after undergoing a liver transplantation. Long-term sequelae of immunosuppression, such as malignancy and infection, continue to be the most common causes of death. This study highlights the necessity for better long-term management of immunosuppression.

Different combinations of the GLIM criteria for patients awaiting a liver transplant: Poor performance for malnutrition diagnosis but a potentially useful prognostic tool.

BACKGROUND & AIMS: Studies using the Global Leadership Initiative on Malnutrition (GLIM) criteria for patients with liver cirrhosis are limited. This study aimed to assess the impact of malnutrition according to the GLIM criteria on the outcomes of patients awaiting a liver transplant (LTx) and compare these criteria with Subjective Global Assessment (SGA). METHODS: This retrospective observational study included adult patients awaiting LTx. Patient clinical data, nutritional status according to various tools including SGA, and resting energy expenditure were assessed. The distinct phenotypic and etiologic criteria provided 36 different GLIM combinations. The GLIM criteria and SGA were compared using the kappa coefficient. The variables associated with mortality before and after the LTx and with a longer length of stay (LOS) after LTx (≥18 days) were assessed by Cox regression and logistic regression analyses, respectively. RESULTS: A total of 152 patients were included [median age 52.0 (interquartile range: 46.5-59.5) years; 66.4% men; 63.2% malnourished according to SGA]. The prevalence of malnutrition according to the GLIM criteria ranged from 0.7% to 30.9%. The majority of the GLIM combinations exhibited poor agreement with SGA. Independent predictors of mortality before and after LTx were presence of ascites or edema (p = 0.011; HR:2.58; CI95%:1.24-5.36), GLIM 32 (PA-phase angle + MELD) (p = 0.026; HR:2.08; CI95%:1.09-3.97), GLIM 33 (PA + MELD-Na≥12) (p = 0.018; HR:2.17; CI95%:1.14-4.13), and GLIM 34 (PA + Child-Pugh) (p = 0.043; HR:1.96; CI95%:1.02-3.77). Malnutrition according to GLIM 28 (handgrip strength + Child-Pugh) was independently associated with a longer LOS (p = 0.029; OR:7.21; CI95%:1.22-42.50). CONCLUSION: The majority of GLIM combinations had poor agreement with SGA, and 4 of the 36 GLIM combinations were independently associated with adverse outcomes.

Predictors of patient and graft survival following pediatric liver transplantation: Long-term analysis of more than 300 cases from single centre.

BACKGROUND: Pediatric liver transplant (PLT) activity has flourished over time although with limited expansion in the graft pool. The study aims to identify pre-transplant factors that predict post-transplant patient and graft survival in the PLT population. METHODS: Retrospective review of PLTs at a single tertiary transplant unit from 2000 to 2019. Univariate and multivariate analyses of pre-transplant factors were performed to identify predictors of patient and graft survival. RESULTS: Two hundred and seventy-six patients received 320 PLTs. The most common cause of graft loss was hepatic artery thrombosis (n = 13, 29.6%). The most common cause of mortality was sepsis (n = 11, 29.7%). Univariate analysis showed that the following variables had a significant (p < .05) impact on patient survival: recipient age, weight, height, graft type (technical variant graft), transplant category (acute liver failure), the era of transplant, and invasive ventilation. The following variables had a significant (p < .05) impact on graft survival: recipient age, weight, height, transplant category (acute liver failure), and the era of transplant. Multivariate analysis precluded the era of transplant as the only significant factor for patient survival; patients transplanted after 2005 had significantly higher patient survival. No independent factor predicting graft survival was identified. For children transplanted after 2005, the only factor that predicted patient survival was pre-transplant invasive ventilation. CONCLUSIONS: Our study suggests that the learning curve and pre-transplant invasive ventilation in the recipient have a significant impact on patient survival. The traditional view of worse outcomes of smaller PLT candidates should be changed.

Readmission After Surgical Resection and Transplantation for Hepatocellular Carcinoma: A Retrospective Cohort Study.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Liver resections and transplantations have increasingly become feasible options for potential cure. These complex surgeries are inherently associated with increased rates of readmission. In the meanwhile, hospital readmission rates are rapidly becoming an important quality of care metric. Therefore, it is very important to understand the effect of 30-day readmission on mortality and the factors associated with increased 30- and 90-day mortality rates. METHODS: This is a retrospective cohort study utilizing data from the National Cancer Database. Patients included were 18 years or older who underwent liver resection or liver transplantation for HCC between 2003 and 2011. Our primary outcomes of interest were 30- and 90-day mortality rates. Our primary independent variable of interest was 30-day readmission. RESULTS: 16 658 patients underwent either a liver resection or transplantation for HCC between 2003 and 2011. For patients with liver transplantations, increased readmission rates were associated with lower risks of 30-day mortality (P = .012) but a trend toward higher 90-day mortality (P = .057). Patients who underwent liver resection for HCC also demonstrated increased readmission rates to be associated with lower risk of 30-day mortality (P = .014) but higher 90-day mortality (P ≤ .001). CONCLUSION: This is the only study to utilize a national database to investigate the association between readmission rates and mortality rates of both liver transplantations and resections for patients with HCC. We demonstrate 30-day readmission to show no increase in 30-day mortality, but rather higher 90-day mortality.

Delayed sequential abdominal wall closure in pediatric liver transplantation to overcome "large for size" scenarios.

BACKGROUND: Primary abdominal wall closure after pediatric liver transplantation (PLT) is neither always possible nor advisable, given the graft-recipient size discrepancy and its potential large-for-size scenario. Our objective was to report the experience accumulated with delayed sequential closure (DSC) guided by Doppler ultrasound control. METHODS: Retrospective analysis of DSC performed from 2013 to March 2020. RESULTS: Twenty-seven DSC (26.5%) were identified out of 102 PLT. Transplant indications and type of grafts were similar among both groups. In patients with DSC, mean weight and GRWR were 9.4 ± 5.5 kg (3.1-26 kg) and 4.7 ± 2.4 (1.9-9.7), significantly lower and higher than the primary closure cohort, respectively. The median time to achieve definitive closure was 6 days (range 3-23 days), and the median number of procedures was 4 (range 2-9). Patients with DSC had longer overall PICU (22.5 ± 16.9 vs. 9.1 ± 9.7 days, p < .05) and hospital stay (33.4 ± 19.1 vs 23, 9 ± 19.8 days (p < .05). These differences are less remarkable if the analysis is performed in a subgroup of patients weighing less than 10 kg. Two patients presented vascular complications (7.4%) within DSC group. No differences were seen when comparing overall, 3-year graft and patient survival (96% and 96% in the DSC group). CONCLUSIONS: DSC is a simple and safe technique to ensure satisfactory clinical outcomes to overcome "large for size" scenarios in PLT. In addition, we were able to avoid using a permanent biological material for closing the abdomen.

Development and validation of a nomogram for predicting acute kidney injury after orthotopic liver transplantation.

BACKGROUND: We aim to develop and validate a nomogram model for predicting severe acute kidney injury (AKI) after orthotopic liver transplantation (OLT). METHODS: A total of 576 patients who received OLT in our center were enrolled. They were assigned to the development and validation cohort according to the time of inclusion. Univariable and multivariable logistic regression using the forward variable selection routine were applied to find risk factors for post-OLT severe AKI. Based on the results of multivariable analysis, a nomogram was developed and validated. Patients were followed up to assess the long-term mortality and development of chronic kidney disease (CKD). RESULTS: Overall, 35.9% of patients were diagnosed with severe AKI. Multivariable logistic regression analysis revealed that recipients' BMI (OR 1.10, 95% CI 1.04-1.17, p = 0.012), hypertension (OR 2.32, 95% CI 1.22-4.45, p = 0.010), preoperative serum creatine (sCr) (OR 0.96, 95% CI 0.95-0.97, p < 0.001), and intraoperative fresh frozen plasm (FFP) transfusion (OR for each 1000 ml increase 1.34, 95% CI 1.03-1.75, p = 0.031) were independent risk factors for post-OLT severe AKI. They were all incorporated into the nomogram. The area under the ROC curve (AUC) was 0.73 (p < 0.05) and 0.81 (p < 0.05) in the development and validation cohort. The calibration curve demonstrated the predicted probabilities of severe AKI agreed with the observed probabilities (p > 0.05). Kaplan-Meier survival analysis showed that patients in the high-risk group stratified by the nomogram suffered significantly poorer long-term survival than the low-risk group (HR 1.92, p < 0.01). The cumulative risk of CKD was higher in the severe AKI group than no severe AKI group after competitive risk analysis (HR 1.48, p < 0.05). CONCLUSIONS: With excellent predictive abilities, the nomogram may be a simple and reliable tool to identify patients at high risk for severe AKI and poor long-term prognosis after OLT.

National time trends in mortality and graft survival following liver transplantation from circulatory death or brainstem death donors.

BACKGROUND: Despite high waiting list mortality rates, concern still exists on the appropriateness of using livers donated after circulatory death (DCD). We compared mortality and graft loss in recipients of livers donated after circulatory or brainstem death (DBD) across two successive time periods. METHODS: Observational multinational data from the United Kingdom and Ireland were partitioned into two time periods (2008-2011 and 2012-2016). Cox regression methods were used to estimate hazard ratios (HRs) comparing the impact of periods on post-transplant mortality and graft failure. RESULTS: A total of 1176 DCD recipients and 3749 DBD recipients were included. Three-year patient mortality rates decreased markedly from 19.6 per cent in time period 1 to 10.4 per cent in time period 2 (adjusted HR 0.43, 95 per cent c.i. 0.30 to 0.62; P < 0.001) for DCD recipients but only decreased from 12.8 to 11.3 per cent (adjusted HR 0.96, 95 per cent c.i. 0.78 to 1.19; P = 0.732) in DBD recipients (P for interaction = 0.001). No time period-specific improvements in 3-year graft failure were observed for DCD (adjusted HR 0.80, 95% c.i. 0.61 to 1.05; P = 0.116) or DBD recipients (adjusted HR 0.95, 95% c.i. 0.79 to 1.14; P = 0.607). A slight increase in retransplantation rates occurred between time period 1 and 2 in those who received a DCD liver (from 7.3 to 11.8 per cent; P = 0.042), but there was no change in those receiving a DBD liver (from 4.9 to 4.5 per cent; P = 0.365). In time period 2, no difference in mortality rates between those receiving a DCD liver and those receiving a DBD liver was observed (adjusted HR 0.78, 95% c.i. 0.56 to 1.09; P = 0.142). CONCLUSION: Mortality rates more than halved in recipients of a DCD liver over a decade and eventually compared similarly to mortality rates in recipients of a DBD liver. Regions with high waiting list mortality may mitigate this by use of DCD livers.

Impact of Perioperative Massive Transfusion on Long Term Outcomes of Liver Transplantation: a Retrospective Cohort Study.

Background: Liver transplantation (LT) is associated with a significant risk of intraoperative hemorrhage and massive blood transfusion. However, there are few relevant reports addressing the long-term impacts of massive transfusion (MT) on liver transplantation recipients. Aim: To assess the effects of MT on the short and long-term outcomes of adult liver transplantation recipients. Methods: We included adult patients who underwent liver transplantation at West China Hospital from January 2011 to February 2015. MT was defined as red blood cell (RBC) transfusion of ≥10 units within 48 hours since the application of LT. Preoperative, intraoperative and postoperative information were collected for data analyzing. We used one-to-one propensity-matching to create pairs. Kaplan-Meier survival analysis was used to compare long-term outcomes of LT recipients between the MT and non-MT groups. Univariate and multivariate logistic regression analyses were performed to evaluate the risk factors associated with MT in LT. Results: Finally, a total of 227 patients were included in our study. After propensity score matching, 59 patients were categorized into the MT and 59 patients in non-MT groups. Compared with the non-MT group, the MT group had a higher 30-day mortality (15.3% vs 0, p=0.006), and a higher incidence of postoperative complications, including postoperative pulmonary infection, abdominal hemorrhage, pleural effusion and severe acute kidney injury. Furthermore, MT group had prolonged postoperative ventilation support (42 vs 25 h, p=0.007) and prolonged durations of ICU (12.9 vs 9.5 d, p<0.001) stay. Multivariate COX regression indicated that massive transfusion (OR: 2.393, 95% CI: 1.164-4.923, p=0.018) and acute rejection (OR: 7.295, 95% CI: 2.108-25.246, p=0.02) were significant risk factors affecting long-term survivals of LT patients. The 1-year and 3-year survival rates patients in MT group were 82.5% and 67.3%, respectively, while those of non-MT group were 93.9% and 90.5%, respectively. The MT group exhibited a lower long-term survival rate than the non-MT group (HR: 2.393, 95% CI: 1.164-4.923, p<0.001). Finally, the multivariate logistic regression revealed that preoperative hemoglobin <118 g/L (OR: 5.062, 95% CI: 2.292-11.181, p<0.001) and intraoperative blood loss ≥1100 ml (OR: 3.212, 95% CI: 1.586-6.506, p = 0.001) were the independent risk factor of MT in patients undergoing LT. Conclusion: Patients receiving MT in perioperative periods of LT had worse short-term and long-term outcomes than the non-MT patients. Massive transfusion and acute rejection were significant risk factors affecting long-term survivals of LT patients, and intraoperative blood loss of over 1100 ml was the independent risk factor of MT in patients undergoing LT. The results may offer valuable information on perioperative management in LT recipients who experience high risk of MT.

Early postoperative mortality in liver transplant recipients involving indications other than hepatocellular carcinoma. A retrospective cohort study / Mortalidad postoperatoria precoz en los receptores de trasplante hepático por indicaciones distintas al carcinoma hepatocelular (non-HCC). Estudio retrospectivo de cohortes

Aims: To analyze the perioperative differences in a consecutive cohort of liver transplant recipients (LTRs) classified according to the indication of transplantation, and assess their impact upon early mortality 90 days after transplantation. Design: A retrospective cohort study was carried out.ScopeA single university hospital. Patients: A total of 892 consecutive adult LTRs were included from January 1995 to December 2017. Recipients with acute liver failure, retransplantation or with grafts from non-brain death donors were excluded. Two cohorts were analyzed according to transplant indication: hepatocellular carcinoma (HCC-LTR) versus non-carcinoma (non-HCC-LTR). Main variables of interest: Recipient early mortality was the primary endpoint. The pretransplant recipient and donor characteristics, surgical time data and postoperative complications were analyzed as independent predictors. ResultsThe crude early postoperative mortality rate related to transplant indication was 13.3% in non-HCC-LTR and 6.6% in HCC-LTR (non-adjusted HR=2.12, 95%CI=1.25–3.60; p=0.005). Comparison of the perioperative features between the cohorts revealed multiple differences. Multivariate analysis showed postoperative shock (HR=2.02, 95%CI=1.26–3.24; p=0.003), early graft vascular complications (HR=4.01, 95%CI=2.45–6.56; p<0.001) and multiorgan dysfunction syndrome (HR=18.09, 95%CI=10.70–30.58; p<0.001) to be independent predictors of mortality. There were no differences in early mortality related to transplant indication (adjusted HR=1.60, 95%CI=0.93–2.76; p=0.086). Conclusions: The crude early postoperative mortality rate in non-HCC-LTR was higher than in HCC-LTR, due to a greater incidence of postoperative complications with an impact upon mortality (shock at admission to intensive care and the development of multiorgan dysfunction syndrome). (AU)

Objetivos: Analizar las diferencias perioperatorias de una cohorte de trasplantados hepáticos (LTR) clasificados por la indicación de trasplante, y evaluar su impacto sobre la mortalidad precoz (90 días postrasplante). Diseño: Estudio de cohorte retrospectivo. Ámbito: Institución universitaria. Pacientes: Desde 1995 hasta 2017 fueron incluidos 892 LTR. Se excluyeron los receptores con fallo hepático agudo, retrasplante o de donantes sin muerte cerebral. Se analizaron 2 cohortes según el motivo del trasplante: carcinoma hepatocelular (HCC-LTR) vs. causas diferente al carcinoma (non-HCC-LTR).Principales variables de interés: La variable principal fue la mortalidad precoz. Las características pretrasplante de receptores, donantes, tiempo quirúrgico y complicaciones postoperatorias se estudiaron como predictores independientes. Resultados: La mortalidad postoperatoria temprana bruta relacionada con la indicación de trasplante fue del 13,3% en non-HCC-LTR y del 6,6% en HCC-LTR (HR no ajustada: 2,12; IC 95%: 1,25-3,60; p=0,005). La comparación de características perioperatorias entre las cohortes mostró múltiples diferencias. El shock postoperatorio (HR: 2,02; IC 95%: 1,26-3,24), complicaciones vasculares tempranas del injerto (HR: 4,01; IC 95%: 2,45-6,56) y síndrome de disfunción multiorgánica (HR: 18,09; IC 95%: 10,70-30,58) fueron predictores independientes de mortalidad. La indicación de trasplante no mostró significación en el análisis multivariante (HR ajustada: 1,60; IC 95%: 0,93-2,76; p=0,086). Conclusiones: La mortalidad postoperatoria temprana bruta en non-HCC-LTR fue mayor que en HCC-LTR debido a la mayor incidencia de complicaciones postoperatorias con impacto en la mortalidad (shock al ingreso en la UCI y aparición del síndrome de disfunción multiorgánica). (AU)

Predictors of mortality and outcomes of liver transplant in spur cell hemolytic anemia.

Spur cell hemolytic anemia (SCHA) is a rare, acquired, nonimmune hemolytic anemia of decompensated cirrhosis. Data describing prognostic impact, outcomes of liver transplant, and clinical hematologic characteristics of SCHA are absent or limited. We performed a multicenter, 24-year observational cohort study of patients with SCHA, retrospectively analyzing hepatic and hematologic parameters, independent predictors of mortality, and long-term outcomes of liver transplant. Sixty-nine patients with SCHA met eligibility for inclusion. The median (interquartile range) age was 53 (42-59) years; 46.4% were female, and 11 (15.9%) received liver transplant. Thirty-nine patients (56.5%) were red blood celltransfusion-dependent. All 11 patients undergoing transplant had rapid and complete resolution of SCHA, with improvement in median hematocrit from 22.1% to 34.6% post-transplant (p = .001) and excellent post-transplant outcomes. In multivariable logistic models adjusting for age, sex, etiology of cirrhosis, active/recent variceal bleeding, and Child-Turcotte-Pugh score, transfusion dependence had an odds ratio (OR) for 90-day mortality of 9.14 (95% CI, 2.46-34.00) and reduced pre-transfusion hematocrit had an OR of 4.73 (95% CI, 1.42-15.82) per 6% decrease; increased red cell transfusion requirement, reduced hemoglobin, increased lactate dehydrogenase, and increased indirect bilirubin were also independently predictive of higher 90-day mortality. Model for end-stage liver disease (MELD)-Na and Child-Turcotte-Pugh scores consistently significantly underestimated 90-day mortality, with standardized mortality ratios (SMRs) >1 across all scores/classes [MELD-Na 20-29, SMR 2.42 (1.18-4.44); Child-Turcotte-Pugh class B, SMR 4.46 (1.64-9.90)]. In conclusion, SCHA is associated with substantial excess mortality than predicted by MELD-Na or Child-Turcotte-Pugh scores and uniformly resolves with liver transplant, without recurrence. Multiple parameters of hemolytic anemia severity independently predict higher 90-day mortality.

MELD 3.0: The Model for End-Stage Liver Disease Updated for the Modern Era.

BACKGROUND & AIMS: The Model for End-Stage Liver Disease (MELD) has been established as a reliable indicator of short-term survival in patients with end-stage liver disease. The current version (MELDNa), consisting of the international normalized ratio and serum bilirubin, creatinine, and sodium, has been used to determine organ allocation priorities for liver transplantation in the United States. The objective was to optimize MELD further by taking into account additional variables and updating coefficients with contemporary data. METHODS: All candidates registered on the liver transplant wait list in the US national registry from January 2016 through December 2018 were included. Uni- and multivariable Cox models were developed to predict survival up to 90 days after wait list registration. Model fit was tested using the concordance statistic (C-statistic) and reclassification, and the Liver Simulated Allocation Model was used to estimate the impact of replacing MELDNa with the new model. RESULTS: The final multivariable model was characterized by (1) additional variables of female sex and serum albumin, (2) interactions between bilirubin and sodium and between albumin and creatinine, and (3) an upper bound for creatinine at 3.0 mg/dL. The final model (MELD 3.0) had better discrimination than MELDNa (C-statistic, 0.869 vs 0.862; P < .01). Importantly, MELD 3.0 correctly reclassified a net of 8.8% of decedents to a higher MELD tier, affording them a meaningfully higher chance of transplantation, particularly in women. In the Liver Simulated Allocation Model analysis, MELD 3.0 resulted in fewer wait list deaths compared to MELDNa (7788 vs 7850; P = .02). CONCLUSION: MELD 3.0 affords more accurate mortality prediction in general than MELDNa and addresses determinants of wait list outcomes, including the sex disparity.

Baseline haemoglobin and thromboelastometry are predictive of red blood cell requirements and one-year mortality in liver transplantation.

BACKGROUND: To determine the predictive capacity of baseline haemoglobin and maxim clot firmness (MCF) EXTEM thromboelastometry for intraoperative red blood cell (RBC) requirements and its influence on mortality. METHODS: 591 adult liver transplant (LT) recipients from ten Spanish centres were reviewed. The main outcomes were the percentage of patients who received RBC and massive transfusion (≥ 6 RBC units), RBC units transfused, and mortality. RESULTS: 76 % received a donor after brain death graft and 24 % a controlled donor after circulatory death graft. Median (interquartile ranges) RBC transfusion was 2 (0-4) units, and 63 % of patients were transfused. Comparing transfused and non-transfused patients, mean (standard deviation) for baseline haemoglobin was 10.4 (2.1) vs. 13.0 (1.9) g/dl (p = 0.001), EXTEM MCF was 51(11) vs. 55(9) mm (p = 0.001). Haemoglobin and EXTEM MCF were inversely associated with the need of transfusion odds ratio (OR) of 0.558 (95 % CI 0.497-0.627, p < 0.001) and OR 0.966 (95 % CI0.945-0.987, p = 0.002), respectively. Pre-operative baseline haemoglobin ≤ 10 g/dL predicted RBC transfusion, sensitivity of 93 % and specificity of 47 %. Massive transfusion (MT) was received by 19 % of patients. Haemoglobin ≤10 g/dL predicted MT with sensitivity 73 % and specificity of 52 %. One-year patient and graft survival were significantly lower in patients who required MT (78 % and 76 %, respectively) vs. those who did not (94 % and 93 %, respectively). DISCUSSION: whereas EXTEM MCF is less dreterminant predicting RBC requirements, efforts are required to improve preoperative haemoglobin up to 10 g/dl in patients awaiting LT.

The Contribution of Serum Complement Component 3 Levels to 90-Day Mortality in Living Donor Liver Transplantation.

The contributions of the complement system have been elucidated in the process of solid organ transplantation, including kidney transplantation. However, the role of complement in liver transplantation is unknown. We sought to elucidate the time-dependent changes of peritransplantational serum complement levels and the relationships with posttransplant outcomes and other immunological biomarkers. We enrolled 82 patients who underwent living-related donor liver transplantation (LDLT). Nine patients (11%) died within 90 days after LDLT (non-survivors). The following immunomarkers were collected preoperatively and at 1, 2, and 4 week(s) after LDLT: serum C3, C4, immunoglobulin G (IgG), and peripheral blood leukocyte populations characterized by CD3, CD4, CD8, CD16, CD19, CD20, CD22, and CD56. Consequently, C3 and C4 increased time-dependently after LDLT. Preoperatively, C3 was negatively correlated with the MELD score, Child-Pugh score, CD16-positive leukocyte percentage, and the CD56-positive leukocyte percentage. Non-survivors had lower levels of C3 at 2 weeks in comparison to survivors (median [interquartile range]: 56 [49-70] mg/dL vs. 88 [71-116] md/dL, p=0.0059). When the cutoff value of C3 at 2 weeks to distinguish non-survivors was set to 71 mg/dL, the sensitivity, specificity, and area under the ROC curve were 87.5%, 75.0%, and 0.80, respectively. A principal component analysis showed an inverse relationship between the C3 and C4 levels and the percentage of CD8-, CD16-, and CD56-positive leukocytes at 1 and 2 week(s). All non-survivors were included in the cluster that showed higher percentages of CD8-, CD16-, and CD56-positive leukocytes at 2 weeks. In conclusion, we demonstrated the relationship between complement, outcomes, and other immunomarkers in LDLT and suggested the usefulness of C3 at 2 weeks after LDLT in distinguishing the mortality.