Effect of recipient age on prioritisation for liver transplantation in the UK: a population-based modelling study.

BACKGROUND: Following the introduction of an algorithm aiming to maximise life-years gained from liver transplantation in the UK (the transplant benefit score [TBS]), donor livers were redirected from younger to older patients, mortality rate equalised across the age range and short-term waiting list mortality reduced. Understanding age-related prioritisation has been challenging, especially for younger patients and clinicians allocating non-TBS-directed livers. We aimed to assess age-related prioritisation within the TBS algorithm by modelling liver transplantation prioritisation based on data from a UK transplant unit and comparing these data with other regions. METHODS: In this population-based modelling study, serum parameters and age at liver transplantation assessment of patients attending the Scottish Liver Transplant Unit, Edinburgh, UK, between December, 2002, and November, 2023, were combined with representative synthetic data to model TBS survival predictions, which were compared according to age group (25-49 years vs ≥60 years), chronic liver disease severity, and disease cause. Models for end-stage liver disease (UKELD [UK], MELD [Eurotransplant region], and MELD 3.0 [USA]) were used as validated comparators of liver disease severity. FINDINGS: Of 2093 patients with chronic liver disease, 1808 (86%) had complete datasets and liver disease parameters consistent with eligibility for the liver transplant waiting list in the UK (UKELD ≥49). Disease severity as assessed by UKELD, MELD, and MELD 3.0 did not differ by age (median UKELD scores of 56 for patients aged ≥60 years vs 56 for patients aged 25-49 years; MELD scores of 16 vs 16; and MELD 3.0 scores of 18 vs 18). TBS increased with advancing age (R=0·45, p<0·0001). TBS predicted that transplantation in patients aged 60 years or older would provide a two-fold greater net benefit at 5 years than in patients aged 25-49 years (median TBS 1317 [IQR 1116-1436] in older patients vs 706 [411-1095] in younger patients; p<0·0001). Older patients were predicted to have shorter survival without transplantation than younger patients (263 days [IQR 144-473] in older patients vs 861 days [448-1164] in younger patients; p<0·0001) but similar survival after transplantation (1599 days [1563-1628] vs 1573 days [1525-1614]; p<0·0001). Older patients could reach a TBS for which a liver offer was likely below minimum criteria for transplantation (UKELD <49), whereas many younger patients were required to have high-urgent disease (UKELD >60). US and Eurotransplant programmes did not prioritise according to age. INTERPRETATION: The UK liver allocation algorithm prioritises older patients for transplantation by predicting that advancing age increases the benefit from liver transplantation. Restricted follow-up and biases in waiting list data might limit the accuracy of these benefit predictions. Measures beyond overall waiting list mortality are required to fully capture the benefits of liver transplantation. FUNDING: None.

Current status of liver transplantation for human immunodeficiency virus-infected patients in mainland China.

According to the report from the Chinese Center for Disease Control and Prevention, the prevalence of human immunodeficiency virus (HIV) infection exceeded 1.2 million individuals by the year 2022, with an annual increase of about 80000 cases. The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%, almost twice the rate of the general population in China. In addition to the well-documented susceptibility to opportunistic infections and new malignancies, HIV infected patients frequently experience liver-related organ damage, with the liver and kidneys being the most commonly affected. This often leads to the development of end-stage liver and kidney diseases. Therefore, organ transplantation has emerged as an important part of active treatment for HIV infected patients. However, the curative effect is not satisfactory. HIV infection has been considered a contraindication for organ transplantation. Until the emergence of highly active anti-retroviral therapy in 1996, the once intractable replication of retrovirus was effectively inhibited. With prolonged survival, the failure of important organs has become the main cause of death among HIV patients. Therefore, transplant centers worldwide have resumed exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion. This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation (LT) in mainland China. To date, our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV, and all but one, who died two months postoperatively due to sepsis and progressive multi-organ failure, have survived. Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions, cytomegalovirus infection, bacteremia, pulmonary infections, acute kidney injury, new-onset cancers, or vascular and biliary complications.

Liver Transplantation at a Small Volume Center-The Role of Network System.

BACKGROUND: Liver transplantation (LT) is typically performed at specialized, high-volume centers. However, some smaller centers also offer liver transplantation services, but their outcomes and safety have been a subject of debate. To overcome these difficulties, we tried to build a Catholic Medical Center (CMC) network to share our experiences and overcome the lack of volume. In this study, we reviewed the overall outcome of patients undergoing LT at a small-volume procedure center, with a focus on patient and graft survival rates. METHODS: Between July 2014 and September 2021, 60 adults underwent LT at Bucheon Saint Mary's Hospital. The overall outcomes were analyzed in terms of perioperative outcomes, complications, and overall survival rate. In addition, the patients were divided into a benign end-stage liver disease (ESLD) group (n = 44) and a hepatocellular carcinoma (HCC) group (n = 16). The baseline characteristics, perioperative outcomes, complications, and overall survival rate were analyzed between the 2 groups. RESULTS: Of a total of 60 LT, living donor liver transplantation (LDLT) was 26, and deceased donor liver transplantation was 34. LDLT was 14 (31.8%) in the ESLD group and 12 (75.0%) in the HCC group. The overall 1-year, 3-year, and 5-year survival rates were 86.7%, 79.7%, and 77.7%, respectively. The survival difference was not statistically significant (P = .214) between the 2 groups. CONCLUSION: We suggest that with appropriate patient selection and adequate resources, LT can be safely performed at smaller centers with the assistance of the CMC network, thus expanding access to this life-saving procedure.

Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis: A Randomized Clinical Trial.

Importance: The benefits of prophylactic antibiotics for hospitalized patients with severe alcohol-related hepatitis are unclear. Objective: To determine the efficacy of amoxicillin-clavulanate, compared with placebo, on mortality in patients hospitalized with severe alcohol-related hepatitis and treated with prednisolone. Design, Setting, and Participants: Multicenter, randomized, double-blind clinical trial among patients with biopsy-proven severe alcohol-related hepatitis (Maddrey function score ≥32 and Model for End-stage Liver Disease [MELD] score ≥21) from June 13, 2015, to May 24, 2019, in 25 centers in France and Belgium. All patients were followed up for 180 days. Final follow-up occurred on November 19, 2019. Intervention: Patients were randomly assigned (1:1 allocation) to receive prednisolone combined with amoxicillin-clavulanate (n = 145) or prednisolone combined with placebo (n = 147). Main Outcome and Measures: The primary outcome was all-cause mortality at 60 days. Secondary outcomes were all-cause mortality at 90 and 180 days; incidence of infection, incidence of hepatorenal syndrome, and proportion of participants with a MELD score less than 17 at 60 days; and proportion of patients with a Lille score less than 0.45 at 7 days. Results: Among 292 randomized patients (mean age, 52.8 [SD, 9.2] years; 80 [27.4%] women) 284 (97%) were analyzed. There was no significant difference in 60-day mortality between participants randomized to amoxicillin-clavulanate and those randomized to placebo (17.3% in the amoxicillin-clavulanate group and 21.3% in the placebo group [P = .33]; between-group difference, -4.7% [95% CI, -14.0% to 4.7%]; hazard ratio, 0.77 [95% CI, 0.45-1.31]). Infection rates at 60 days were significantly lower in the amoxicillin-clavulanate group (29.7% vs 41.5%; mean difference, -11.8% [95% CI, -23.0% to -0.7%]; subhazard ratio, 0.62; [95% CI, 0.41-0.91]; P = .02). There were no significant differences in any of the remaining 3 secondary outcomes. The most common serious adverse events were related to liver failure (25 in the amoxicillin-clavulanate group and 20 in the placebo group), infections (23 in the amoxicillin-clavulanate group and 46 in the placebo group), and gastrointestinal disorders (15 in the amoxicillin-clavulanate group and 21 in the placebo group). Conclusion and Relevance: In patients hospitalized with severe alcohol-related hepatitis, amoxicillin-clavulanate combined with prednisolone did not improve 2-month survival compared with prednisolone alone. These results do not support prophylactic antibiotics to improve survival in patients hospitalized with severe alcohol-related hepatitis. Trial Registration: ClinicalTrials.gov Identifier: NCT02281929.

Travel distance and social vulnerability index: Impact on liver-related mortality among patients with end-stage liver disease.

INTRODUCTION: The reasons for the geographic disparities in liver-related mortality across the US remain ill-defined. We sought to investigate the impact of travel distance to liver transplantation (LT) programs and social vulnerability on county differences in liver-related mortality. METHODS: Data on LT registrants were obtained from the Scientific Registry of Transplant Recipients Standard Analytic Files (SRTR SAFs) between 2004 and 2019. Liver-related mortality data were obtained from the Center for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) platform. Spatial epidemiological clustering of county-level LT registration and liver-related mortality rates was determined using local Moran's I. Comparison analyses assessed social vulnerability index (SVI) and travel distance within various county clusters. RESULTS: Among 151 864 LT waitlist registrants who were diagnosed with liver disease due to hepatitis C virus (HCV) or hepatitis B virus (HBV) (n = 68 479, 45.1%), alcohol (n = 38 328, 25.2%), non-alcoholic steatohepatitis (NASH) (n = 17 485, 11.5%), liver tumors (n = 16 644, 11.0%), and other diseases (n = 10 928, 7.2%), median SVI was 59.3 (IQR, 40.1-83.4). SVI (76.2 vs. 24.3, p < .001) was greater in the highest versus lowest liver-related mortality quartiles. The travel distances to LT centers (143.1 miles vs. 107.2 miles, p < .001) was longer in the lowest versus highest LT registration quartiles. Counties with low LT registration rates and high liver-related mortality rates were associated with long travel distances and high SVI. In contrast, while counties with high LT registration rates and high liver-related mortality rates had comparable SVI, travel distance was relatively shorter. CONCLUSION: Counties with greater SVIs were associated with higher liver-related mortality, with the highest SVI  counties having the highest overall liver-related mortality. Longer travel distances were associated with higher liver-related mortality. These findings highlight the impact of social determinants of health (SDOH) on liver disease outcomes.

MELD-GRAIL-Na Is a Better Predictor of Mortality Than MELD in Korean Patients with Cirrhosis.

Background and Objectives: The Child-Pugh (CP) score and Model for End-Stage Liver Disease (MELD) are classical systems for predicting mortality in patients with liver cirrhosis (LC). The MELD-GFR assessment in liver disease-sodium (MELD-GRAIL-Na) was designed to better reflect renal function and, therefore, provide better mortality predictions. This study aimed to compare the prediction accuracy of MELD-GRAIL-Na compared to CP and MELD in predicting short-term (1- and 3-month) mortality in Korean patients. Materials and Methods: Medical records of patients with LC admitted to the Konkuk University Hospital from 2015 to 2020 were retrospectively reviewed. Predictive values of the CP, MELD, and MELD-GRAIL-Na for 1-month and 3-month mortality were calculated using the area under the receiver operating curve (AUROC) and were compared using DeLong's test. Results: In total, 1249 patients were enrolled; 102 died within 1 month, and 146 within 3 months. AUROCs of CP, MELD, and MELD-GRAIL-Na were 0.831, 0.847, and 0.857 for 1-month mortality and 0.837, 0.827, and 0.835 for 3-month mortality, respectively, indicating no statistical significance. For patients with CP classes B and C, AUROCs of CP, MELD, and MELD-GRAIL-Na were 0.782, 0.809, and 0.825 for 1-month mortality and 0.775, 0.769, and 0.786 for 3-month mortality, respectively. There was a significant difference between CP and MELD-GRAIL-Na in predicting 1-month mortality (p = 0.0428) and between MELD and MELD-GRAIL-Na in predicting 1-month (p = 0.0493) and 3-month mortality (p = 0.0225). Conclusions: Compared to CP and MELD, MELD-GRAIL-Na was found to be a better and more useful system for evaluating short-term (1- and 3-month) mortality in Korean patients with cirrhosis, especially those with advanced cirrhosis (CP class B and C).

Prognosis of Children Undergoing Liver Transplantation: A 30-Year European Study.

OBJECTIVES: The European Liver Transplant Registry has been collecting data on virtually all pediatric liver transplant (PLT) procedures in Europe since 1968. We analyzed patient outcome over time and identified parameters associated with long-term patient outcome. METHODS: Participating centers and European organ-sharing organizations provided retrospective data to the European Liver Transplant Registry. To identify trends, data were grouped into consecutive time spans: era A: before 2000, era B: 2000 to 2009, and the current era, era C: since 2010. RESULTS: From June 1968 until December 2017, 16 641 PLT were performed on 14 515 children by 133 centers. The children <7 years of age represented 58% in era A, and 66% in the current era (P <.01). The main indications for PLT were congenital biliary diseases (44%) and metabolic diseases (18%). Patient survival at 5 years is currently 86% overall and 97% in children who survive the first year after PLT. The survival rate has improved from 74% in era A to 83% in era B and 85% in era C (P <.0001). Low-volume centers (<5 PLT/year) represented 75% of centers but performed only 19% of PLT and were associated with a decreased survival rate. In the current era, however, survival rates has become irrespective of volume. Infection is the leading cause of death (4.1%), followed by primary nonfunction of the graft (1.4%). CONCLUSIONS: PLT has become a highly successful medical treatment that should be considered for all children with end-stage liver disease. The main challenge for further improving the prognosis remains the early postoperative period.

Acute Kidney Injury in Patients with Liver Cirrhosis: Prevalence, Predictors, and In-Hospital Mortality at a District Hospital in Ghana.

BACKGROUND: Acute kidney injury (AKI) is one of the most severe complications of cirrhosis and portends an ominous prognosis with an estimated mortality of about 50% in a month and 65% within a year. Infection and hypovolemia have been found to be the main precipitating factors of AKI in liver cirrhosis. Early detection and treatment of AKI may improve outcomes. AKI in patients with liver cirrhosis in Ghana and their impact on inpatient mortality are largely unknown. This study was aimed at determining the prevalence, precipitating factors, predictors, and in-hospital mortality of AKI in patients with liver cirrhosis admitted to a district hospital in Ghana. METHODS: Consecutive hospitalized patients with liver cirrhosis from 1 January 2018 to 30 April 2020 were recruited. Patient's demographic data and clinical features were collected using a standardized questionnaire. Biochemical and haematological tests as well as abdominal ultrasound scans were done for all patients. All patients were then followed up until discharge or death. RESULTS: There were 117 (65.4%) males out of the 179 patients with a mean age of 49.94 and 45.84 years for those with and without AKI, respectively. The prevalence of AKI was 27.9% (50/179). Out of 50 participants with AKI, 64.0% (32/50) died, contributing 41.0% of all in-patient mortality amongst participants. There was a significant association between AKI and death (p ≤ 0.001). The major precipitating factors of AKI were infections (60.0%), hypovolemia (20.0%) due to gastrointestinal bleeding and gastroenteritis, and refractory ascites (16.0%). Alkaline phosphatase, INR, model for end-stage liver disease sodium, sodium, and blood urea nitrogen were independent predictors of AKI. CONCLUSION: AKI was common among patients with liver cirrhosis with high in-patient mortality. Identification of these precipitants and independent predictors of AKI may lead to prompt and targeted treatment with reduction in patient mortality.

The use of tracheostomy to support critically ill children receiving orthotopic liver transplantation: a single-center experience.

BACKGROUND: Children with end-stage liver disease and multi-organ failure, previously considered as poor surgical candidates, can now benefit from liver transplantation (LT). They often need prolonged mechanical ventilation (MV) post-LT and may need tracheostomy to advance care. Data on tracheostomy after pediatric LT are lacking. METHOD: Retrospective chart review of children who required tracheostomy in the peri-LT period in a large, freestanding quaternary children's hospital from 2014 to 2019. RESULTS: Out of 205 total orthotopic LTs performed in 200 children, 18 (9%) required tracheostomy in the peri-transplant period: 4 (2%) pre-LT and 14 (7%) post-LT. Among those 14 needing tracheostomy post-LT, median age was 9 months [IQR = 7, 14] at LT and 10 months [9, 17] at tracheostomy. Nine (64%) were infants and 12 (85%) were cirrhotic at the time of LT. Seven (50%) were intubated before LT. Median MV days prior to LT was 23 [7, 36]. Eight (57%) patients received perioperative continuous renal replacement therapy (CRRT). The median MV days from LT to tracheostomy was 46 [33, 56]; total MV days from initial intubation to tracheostomy was 57 [37, 66]. Four (28%) children died, of which 3 (21%) died within 1 year of transplant. Total ICU and hospital length of stay were 92 days [I72, 126] and 177 days [115, 212] respectively. Among survivors, 3/10 (30%) required MV at home and 8/10 (80%) were successfully decannulated at 400 median days [283, 584]. CONCLUSION: Tracheostomy though rare after LT remains a feasible option to support and rehabilitate critically ill children who need prolonged MV in the peri-LT period.

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.

Recovery and outcomes of patients denied early liver transplantation for severe alcohol-associated hepatitis.

BACKGROUND AND AIMS: Liver transplantation (LT) in alcohol-associated hepatitis (AH) remains controversial, in part because spontaneous recovery (SR) can occur. There is a paucity of data on SR in patients with severe AH who undergo LT evaluation. The purpose of this study was to determine factors associated with SR and survival in patients with severe AH who undergo LT evaluation. APPROACH AND RESULTS: This is a retrospective study of ALD patients with Model for End-Stage Liver Disease (MELD) >25 and <90 days abstinence who underwent LT evaluation at a single center between 2012 and 2018. One hundred forty-four patients (median age, 45.5 years; 68.1% male) were included. Forty-nine (34%) underwent LT and 95 (66%) patients did not undergo LT, and of those, 34 (23.6%) experienced SR. Factors associated with recovery were younger age (OR, 0.92; p = 0.004), lower index international normalized ratio (INR; 0.31; p = 0.03), and lower peak MELD (OR, 0.83; p = 0.02). Only 7 patients (20.6%) achieved a compensated state with a MELD <15 and absence of therapy for ascites or HE. Survival was improved in patients who underwent early LT when compared to SR. Survival was impaired in SR following relapse to alcohol use when compared to SR patients who abstained and LT recipients. Among all 6-month survivors of AH, alcohol use trended toward an association with mortality (HR, 2.05; p = 0.17), but only LT was associated with decreased mortality risk (HR, 0.20; p = 0.005). CONCLUSIONS: SR from AH after LT evaluation is associated with age, index INR, and lower peak MELD. Most recovered patients continue to experience end-stage complications. LT is the only factor associated with lower mortality.

Racial/ethnic disparities in wait-list outcomes are only partly explained by socioeconomic deprivation among children awaiting liver transplantation.

BACKGROUND AND AIMS: Racial/ethnic minority children have worse liver transplant (LT) outcomes. We evaluated whether neighborhood socioeconomic deprivation affected associations between race/ethnicity and wait-list mortality. APPROACH AND RESULTS: We included children (age <18) listed 2005-2015 in the Scientific Registry of Transplant Recipients. We categorized patients as non-Hispanic White, Black, Hispanic, and other. We matched patient ZIP codes to a neighborhood socioeconomic deprivation index (range, 0-1; higher values indicate worse deprivation). Primary outcomes were wait-list mortality, defined as death/delisting for too sick, and receipt of living donor liver transplant (LDLT). Competing risk analyses modeled the association between race/ethnicity and wait-list mortality, with deceased donor liver transplant (DDLT) and LDLT as competing risks, and race/ethnicity and LDLT, with wait-list mortality and DDLT as competing risks. Of 7716 children, 17% and 24% identified as Black and Hispanic, respectively. Compared to White children, Black and Hispanic children had increased unadjusted hazard of wait-list mortality (subhazard ratio [sHR], 1.44; 95% CI, 1.18, 1.75 and sHR, 1.48; 95% CI, 1.25, 1.76, respectively). After adjusting for neighborhood deprivation, insurance, and listing laboratory Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease, Black and Hispanic children did not have increased hazard of wait-list mortality (sHR, 1.12; 95% CI, 0.91, 1.39 and sHR, 1.21; 95% CI, 1.00, 1.47, respectively). Similarly, Black and Hispanic children had a decreased likelihood of LDLT (sHR, 0.58; 95% CI, 0.45, 0.75 and sHR, 0.61; 95% CI, 0.49, 0.75, respectively). Adjustment attenuated the effect of Black and Hispanic race/ethnicity on likelihood of LDLT (sHR, 0.79; 95% CI, 0.60, 1.02 and sHR, 0.89; 95% CI, 0.70, 1.11, respectively). CONCLUSIONS: Household and neighborhood socioeconomic factors and disease severity at wait-list entry help explain racial/ethnic disparities for children awaiting transplant. A nuanced understanding of how social adversity contributes to wait-list outcomes may inform strategies to improve outcomes.

Impact of MELD 30-allocation policy on liver transplant outcomes in Italy.

BACKGROUND & AIMS: In Italy, since August 2014, liver transplant (LT) candidates with model for end-stage liver disease (MELD) scores ≥30 receive national allocation priority. This multicenter cohort study aims to evaluate time on the waiting list, dropout rate, and graft survival before and after introducing the macro-area sharing policy. METHODS: A total of 4,238 patients registered from 2010 to 2018 were enrolled and categorized into an ERA-1 Group (n = 2,013; before August 2014) and an ERA-2 Group (n = 2,225; during and after August 2014). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of receiving a LT or death between the two eras. The Fine-Gray model was used to estimate the HR for dropout from the waiting list and graft loss, considering death as a competing risk event. A Fine-Gray model was also used to estimate risk factors of graft loss. RESULTS: Patients with MELD ≥30 had a lower median time on the waiting list (4 vs.12 days, p <0.001) and a higher probability of being transplanted (HR 2.27; 95% CI 1.78-2.90; p = 0.001) in ERA-2 compared to ERA-1. The subgroup analysis on 3,515 LTs confirmed ERA-2 (odds ratio 0.56; 95% CI 0.46-0.68; p = 0.001) as a protective factor for better graft survival rate. The protective variables for lower dropouts on the waiting list were: ERA-2, high-volume centers, no competition centers, male recipients, and hepatocellular carcinoma. The protective variables for graft loss were high-volume center and ERA-2, while MELD ≥30 remained related to a higher risk of graft loss. CONCLUSIONS: The national MELD ≥30 priority allocation was associated with improved patient outcomes, although MELD ≥30 was associated with a higher risk of graft loss. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes. CLINICAL TRIAL NUMBER: NCT04530240 LAY SUMMARY: Italy introduced a new policy in 2014 to give national allocation priority to patients with a model for end-stage liver disease (MELD) score ≥30 (i.e. very sick patients). This policy has led to more liver transplants, fewer dropouts, and shorter waiting times for patients with MELD ≥30. However, a higher risk of graft loss still burdens these cases. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes.

The MELD Score Is Superior to the Maddrey Discriminant Function Score to Predict Short-Term Mortality in Alcohol-Associated Hepatitis: A Global Study.

INTRODUCTION: Several scoring systems predict mortality in alcohol-associated hepatitis (AH), including the Maddrey discriminant function (mDF) and model for end-stage liver disease (MELD) score developed in the United States, Glasgow alcoholic hepatitis score in the United Kingdom, and age, bilirubin, international normalized ratio, and creatinine score in Spain. To date, no global studies have examined the utility of these scores, nor has the MELD-sodium been evaluated for outcome prediction in AH. In this study, we assessed the accuracy of different scores to predict short-term mortality in AH and investigated additional factors to improve mortality prediction. METHODS: Patients admitted to hospital with a definite or probable AH were recruited by 85 tertiary centers in 11 countries and across 3 continents. Baseline demographic and laboratory variables were obtained. The primary outcome was all-cause mortality at 28 and 90 days. RESULTS: In total, 3,101 patients were eligible for inclusion. After exclusions (n = 520), 2,581 patients were enrolled (74.4% male, median age 48 years, interquartile range 40.9-55.0 years). The median MELD score was 23.5 (interquartile range 20.5-27.8). Mortality at 28 and 90 days was 20% and 30.9%, respectively. The area under the receiver operating characteristic curve for 28-day mortality ranged from 0.776 for MELD-sodium to 0.701 for mDF, and for 90-day mortality, it ranged from 0.773 for MELD to 0.709 for mDF. The area under the receiver operating characteristic curve for mDF to predict death was significantly lower than all other scores. Age added to MELD obtained only a small improvement of AUC. DISCUSSION: These results suggest that the mDF score should no longer be used to assess AH's prognosis. The MELD score has the best performance in predicting short-term mortality.

Frailty is associated with increased risk of cirrhosis disease progression and death.

BACKGROUND AND AIMS: The Liver Frailty Index (LFI) is a well-studied tool that evaluates frailty in patients with cirrhosis. Consisting of grip strength, chair stands, and balance testing, the LFI has been associated with increased mortality in patients awaiting liver transplant. We aimed to extend our understanding of frailty in cirrhosis by exploring the relationship between the LFI and the risk of (1) cirrhosis progression, (2) mortality, and (3) unplanned hospitalizations, in both compensated and decompensated disease. APPROACH AND RESULTS: Adult patients with cirrhosis from four centers in North America and one in India were included. Frailty was measured at baseline using the LFI and categorized as robust (LFI < 3.2), prefrail (LFI 3.2-4.5), and frail (LFI > 4.5). Progression of cirrhosis was defined by an increase in clinical stage, ranging from 1 to 5, from baseline using the D'Amico classification. Factors associated with progression, mortality, and hospitalizations were evaluated using multivariate regression models, with transplant as a competing risk. In total, 822 patients with cirrhosis were included. Average Model for End-Stage Liver Disease (MELD) score was 15.5 ± 6.0. In patients with compensated cirrhosis, being frail versus robust was associated with increased risk of progression to the next cirrhosis stage or to death (HR, 2.45; 95% CI, 1.14-5.29) and with an increased risk of unplanned hospitalizations (2.32; 95% CI, 1.13-4.79), after adjusting for age, sex, and MELD score. Similar HRs were observed in patients with decompensated cirrhosis. CONCLUSIONS: Frailty was an independent predictor of cirrhosis progression or death and unplanned hospitalization across patients with compensated and decompensated cirrhosis. Future studies are needed to evaluate the possibility of slowing cirrhosis disease progression by reversing or preventing frailty.

Factors determining the mortality in cirrhosis patients with invasive candidiasis: A systematic review and meta-analysis.

The impact of invasive candidiasis (IC) on the outcomes in the non-conventional high-risk cirrhosis population is poorly characterized. Therefore, we reviewed the outcomes and their influencing factors in cirrhosis patients with IC. PubMed, Embase, Ovid, CINHAL, and Web of Science were searched for full-text observational studies describing mortality due to IC in cirrhosis. We did a systematic review and random-effects meta-analysis to pool the point-estimate and comparative-odds of mortality. The estimate's heterogeneity was explored on sub-groups, outliers-test, and meta-regression. We evaluated the asymmetry in estimates on funnel plot and Eggers regression. Quality of studies was assessed on the New-Castle Ottawa scale. Of 3143 articles, 13 studies (611 patients) were included (good/fair quality: 6/7). IC patients were sick with a high model for end-stage liver disease (MELD: 27.0) and long hospital stay (33.2 days). The pooled-mortality was 54.7% (95% CI: 41.3--67.5), I2: 80%, P < 0.01. Intensive care unit (ICU) admission (P < 0.001), site of infection; viz. peritonitis and candidemia (P = 0.014) and high MELD of cases (P = 0.029) were predictors of high mortality. The odds of mortality due to IC was 4.4 times higher than controls and was 8.5 and 3.3 times higher than non-infected, and bacterially-infected controls. Studies in ICU-admitted (OR: 5.0) or acute-on-chronic liver failure (ACLF, OR: 6.3) patients had numerically higher odds of mortality than all-hospitalized cirrhosis patients (OR: 4.0). In conclusion, substantially high mortality is reported in cirrhosis patients with IC. ICU admission, ACLF, high MELD, peritonitis, and candidemia are key factors determining high mortality in cirrhosis patients with IC. LAY SUMMARY: We report a high mortality rate of 55% in patients with liver cirrhosis and invasive candidiasis. Higher odds (4.4 times) of death, especially in patients with ACLF (6.3 times) or ICU admission (5.0 times) were seen. Candida peritonitis and candidemia are associated with high mortality in cirrhosis.

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.

Expanding the Donor Pool: First Use of Hepatitis B Virus Nat Positive Solid Organ Allografts Into Seronegative Recipients.

OBJECTIVES: The aim of this study was to assess the 1-year safety and effectiveness of HBV Nucleic Acid Test positive (HBV NAT+) allografts in seronegative kidney transplant (KT) and liver transplant (LT) recipients. SUMMARY BACKGROUND DATA: Despite an ongoing organ shortage, the utilization of HBV NAT+ allografts into seronegative recipients has not been investigated. METHODS: From January 2017 to October 2020, a prospective cohort study was conducted among consecutive KT and LT recipients at a single institution. Primary endpoints were post-transplant HBV viremia, graft and patient survival. RESULTS: With median follow-up of 1-year, there were no HBV-related complications in the 89 HBV NAT+ recipients. Only 9 of 56 KTs (16.1%) and 9 of 33 LTs (27.3%) experienced post-transplant HBV viremia at a median of 185 (KT) and 269 (LT) days postoperatively. Overall, viremic episodes resolved to undetected HBV DNA after a median of 80 days of entecavir therapy in 16 of 18 recipients. Presently, 100% of KT recipients and 93.9% of LT recipients are HBV NAT- with median follow-up of 13 months, whereas 0 KT and 8 LT (24.2%) recipients are HBV surface antigen positive indicating chronic infection. KT and LT patient and allograft survival were not different between HBV NAT+ and HBV NAT- recipients (P > 0.05), whereas HBV NAT+ KT recipients had decreased waitlist time and pretransplant duration on dialysis (P < 0.01). CONCLUSIONS: This is the largest series describing the transplantation of HBV NAT+ kidney and liver allografts into HBV seronegative recipients without chronic HBV viremia or decreased 1-year patient and graft survival. Increasing the utilization of HBV NAT+ organs in nonviremic recipients can play a role in decreasing the national organ shortage.

Sarcopenia adversely impacts postoperative complications in living-donor liver transplantation recipients.

Despite technological and immunological innovations, living-donor liver transplant (LDLT) recipients still face substantial risk of postoperative complications. Sarcopenia is being recognized more and more as a biomarker that correlates with poor outcomes in surgical patients. The purpose of this study was to evaluate the relationship between sarcopenia and significant surgical complications in LDLT recipients. This retrospective review included patients who had received LDLT at our institute from 2005 to 2017. Sarcopenia was assessed using the psoas muscle index (PMI) in cross-sectional images. ROC curve analysis was used to determine the ability of PMI to predict postoperative complications. Correlations between major postoperative complications and sarcopenia were evaluated using regression analysis. A total of 271 LDLT recipients were included. No significant differences were found between PMI and major postoperative complications in male patients. Female recipients with major postoperative complications had significantly lower mean PMI values (P = 0.028), and the PMI cut-off value was 2.63 cm2/m2. Postoperative massive pleural effusion requiring pigtail drainage occurred more frequently in the sarcopenia group than in the non-sarcopenia group (P = 0.003). 1-, 3-, 5- and 10-year overall survival rates in female were significantly poorer in the sarcopenia group (n = 14) compared with the non-sarcopenia group (n = 108), at 92.9% versus 97.2%, 85.7% versus 95.4%, 85.7% versus 92.5% and 70.1 versus 82.0%, respectively (P = 0.041) and 94.6%, 89.9%, 85.9% and 78.5% in male patients. Sarcopenia is associated with a significantly higher risk of major postoperative complications in females. PMI and sarcopenia together are predictive of major postoperative complications and survival rates in female LDLT recipients.

Automated Measurements of Body Composition in Abdominal CT Scans Using Artificial Intelligence Can Predict Mortality in Patients With Cirrhosis.

Body composition measures derived from already available electronic medical records (computed tomography [CT] scans) can have significant value, but automation of measurements is needed for clinical implementation. We sought to use artificial intelligence to develop an automated method to measure body composition and test the algorithm on a clinical cohort to predict mortality. We constructed a deep learning algorithm using Google's DeepLabv3+ on a cohort of de-identified CT scans (n = 12,067). To test for the accuracy and clinical usefulness of the algorithm, we used a unique cohort of prospectively followed patients with cirrhosis (n = 238) who had CT scans performed. To assess model performance, we used the confusion matrix and calculated the mean accuracy of 0.977 ± 0.02 (0.975 ± 0.018 for the training and test sets, respectively). To assess for spatial overlap, we measured the mean intersection over union and mean boundary contour scores and found excellent overlap between the manual and automated methods with mean scores of 0.954 ± 0.030, 0.987 ± 0.009, and 0.948 ± 0.039 (0.983 ± 0.013 for the training and test set, respectively). Using these automated measurements, we found that body composition features were predictive of mortality in patients with cirrhosis. On multivariate analysis, the addition of body composition measures significantly improved prediction of mortality for patients with cirrhosis over Model for End-Stage Liver Disease alone (P < 0.001). Conclusion: The measurement of body composition can be automated using artificial intelligence and add significant value for incidental CTs performed for other clinical indications. This is proof of concept that this methodology could allow for wider implementation into the clinical arena.