IL-1 Signal Inhibition in Alcohol-Related Hepatitis: A Randomized, Double-Blind, Placebo-Controlled Trial of Canakinumab.

BACKGROUND AND AIMS: Short-term mortality in alcohol-related hepatitis (AH) is high, and no current therapy results in durable benefit. A role for interleukin (IL)-1ß has been demonstrated in the pathogenesis of alcohol-induced steatohepatitis. This study explored the safety and efficacy of canakinumab (CAN), a monoclonal antibody targeting IL-1ß, in the treatment of patients with AH. METHODS: Participants with biopsy-confirmed AH and discriminant function ≥32 but Model for End-Stage Liver Disease ≤27 were randomly allocated 1:1 to receive either CAN 3 mg/kg or placebo (PBO). Liver biopsies were taken before and 28 days after treatment. The primary endpoint was the overall histological improvement in inflammation analyzed by the modified intention-to-treat principle. RESULTS: Fifty-seven participants were randomized: 29 to CAN and 28 to PBO. Two participants had histology that did not corroborate the clinical diagnosis. Of the remaining 55 participants, paired histology data were evaluable from 48 participants. In CAN-treated participants, 14 (58%) of 24 demonstrated histological improvement compared with 10 (42%) of 24 in the PBO group (P = .25). There was no improvement in prognostic scores of liver function. Four (7%) of the 55 participants died within 90 days, 2 in each group. The number of serious adverse events was similar between CAN vs PBO. In post hoc exploratory analyses after adjustment for baseline prognostic factors, CAN therapy was associated with overall histological improvement (P = .04). CONCLUSIONS: CAN therapy in severe AH participants with Model for End-Stage Liver Disease ≤27 did not alter biochemical or clinical outcomes compared with PBO. Nonsignificant histological improvements did not translate into clinical benefit. EudraCT, Number: 2017-003724-79; ClinicalTrials.gov, Number: NCT03775109.

Application of model for end-stage liver disease as disease classification in cardiac valve surgery: a retrospective study based on the INSPIRE database.

Background: Model for end-stage liver disease (MELD) is an effective predictive marker for renal, hepatic, and cardiac dysfunctions. In this study, we explore the correlation between MELD scores and the outcomes of patients undergoing cardiac valve surgery. Methods: We conducted a retrospective analysis of clinical data from patients who underwent cardiac valve surgery, encompassing procedures on the aortic valve, mitral valve, and tricuspid valve, using the Informative Surgical Patient dataset for Innovative Research Environment (INSPIRE) database, we conducted receiver operating characteristic (ROC) analyses on the study participants and chose MELD as the primary scoring tool for our study due to its optimal area under the curve (AUC), patients were stratified into high (MELD ≥18) and low (MELD <18) groups based on the determined cutoff value. The perioperative clinical data of the two groups were compared. Results: The analysis revealed 751 patients in the low MELD group (75.5%) and 244 patients (24.5%) in the high MELD group. Patients in the high MELD group exhibited a lower body mass index (BMI) compared to those in the low MELD group. In comparison to the low MELD group, the high MELD group exhibited a higher rate of emergency surgery (10.66% vs. 5.99%, P=0.01), along with prolonged anesthesia time, surgery time, and cardiopulmonary bypass (CPB) time. Regarding clinical prognosis, the high MELD group demonstrated a higher 28-day mortality rate (10.66% vs. 0.8%, P<0.001), as also observed in the analysis of three valve subgroups. Additionally, the high MELD group experienced longer hospitalization and intensive care unit (ICU) stay, and a higher proportion of patients requiring mechanical circulatory support, including intra-aortic balloon pump (IABP) assist (14.75% vs. 3.86%, P<0.001), extracorporeal membrane oxygenation (ECMO) assist (7.38% vs. 0.8%, P<0.001), and continuous renal replacement therapy (CRRT) (27.87% vs. 1.46%, P<0.001) post-surgery. The Kaplan-Meier survival curves illustrated a significantly lower mortality rate in the low MELD group compared to the high MELD group, with highly significant statistical differences (P<0.001). Conclusions: The MELD score demonstrates a robust predictive value for clinical outcomes following cardiac valve surgery, underscoring its utility as a viable metric for disease stratification research.

Developing a nomogram for forecasting the 28-day mortality rate of individuals with bleeding esophageal varices using model for end-stage liver disease scores.

BACKGROUND: This study aimed to create a nomogram using the model for end-stage liver disease (MELD) that can better predict the risk of 28-day mortality in patients with bleeding esophageal varices. METHODS: Data on patients with bleeding esophageal varices were retrospectively collected from the Medical Information Mart for Intensive Care database. Variables were selected using the least absolute shrinkage and selection operator logistic regression model and were used to construct a prognostic nomogram. The nomogram was evaluated against the MELD model using various methods, including receiver operating characteristic (ROC) curve analysis, calibration plotting, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). RESULTS: A total of 280 patients were included in the study. The patient's use of vasopressin and norepinephrine, respiratory rate, temperature, mean corpuscular volume, and MELD score were included in the nomogram. The area under the ROC curve, NRI, IDI, and DCA of the nomogram indicated that it performs better than the MELD alone. CONCLUSION: A nomogram was created that outperformed the MELD score in forecasting the risk of 28-day mortality in individuals with bleeding esophageal varices.

Hepatopulmonary Syndrome: A Comprehensive Review.

Hepatopulmonary syndrome (HPS) is defined by abnormally dilated blood vessels and shunts within the lungs, leading to impaired oxygen exchange. This condition results from intricate interactions between the liver, the gastrointestinal system, and the lungs. This complex system primarily affects pulmonary endothelial, immunomodulatory, and respiratory epithelial cells. Consequently, this contributes to pathological pulmonary changes characteristic of HPS. A classification system based on the severity of oxygen deficiency has been proposed for grading the physiological dysfunction of HPS. Contrast-enhanced echocardiography is considered the primary radiological evaluation for identifying abnormal blood vessel dilations within the lungs, which, combined with an elevated alveolar-arterial gradient, is essential for making the diagnosis. Liver transplantation is the sole effective definitive treatment that can reverse the course of the condition. Despite often being symptomless, HPS carries a significant risk of mortality before transplantation, regardless of the severity of liver disease. Meanwhile, there is varying data regarding survival rates following liver transplantation. The adoption of the model for end-stage liver disease (MELD) standard exception policy has notably improved the results for individuals with HPS compared to the period before MELD was introduced. This review offers a summary of the present understanding, highlighting recent advancements in the diagnosis and treatment of HPS. Furthermore, it aims to augment comprehension of the condition's fundamental mechanisms through insights derived from experimental models and translational research.

Changing landscape of liver transplant in the United States-time for a new innovative way to define and utilize the "non-standard liver allograft"-a proposal.

Since the first liver transplant was performed over six decades ago, the landscape of liver transplantation in the US has seen dramatic evolution. Numerous advancements in perioperative and operative techniques have resulted in major improvements in graft and patient survival rates. Despite the increase in transplants performed over the years, the waitlist mortality rate continues to remain high. The obesity epidemic and the resultant metabolic sequelae continue to result in more marginal donors and challenging recipients. In this review, we aim to highlight the changing characteristics of liver transplant recipients and liver allograft donors. We focus on issues relevant in successfully transplanting a high model for end stage liver disease recipient. We provide insights into the current use of terms and definitions utilized to discuss marginal allografts, discuss the need to look into more consistent ways to describe these organs and propose two new concepts we coin as "Liver Allograft Variables" (LAV) and "Liver Allograft Composite Score" (LACS) for this. We discuss the development of spectrum of risk indexes as a dynamic tool to characterize an allograft in real time. We believe that this concept has the potential to optimize the way we allocate, utilize and transplant livers across the US.

Outcome Predictors of Acute-on-Chronic Liver Failure: A Narrative Review.

Complications of acute-on-chronic liver failure (ACLF) include increased short-term mortality. Extrahepatic organ failures result from chronic liver disease and acute hepatic injury. This combination characterizes end-stage liver disease. Its rapid progression makes it challenging for hepatologists and intensivists to treat. The varied definitions of this condition lead to varied clinical presentations. Hepatic or extrahepatic failures are more prevalent in chronic hepatitis B or cirrhosis patients who receive an additional injury. Numerous intensity parameters and prognosis ratings, including those for hepatitis B virus (HBV), have been developed and verified for various patients and causes of the disease. Liver regeneration, liver transplantation (LT), or antiviral therapy for HBV-related ACLF are the main treatment aims for various organ failures. LT is the best treatment for HBV-ACLF. In some HBV-related ACLF patients, nucleos(t)ide analogs and artificial liver assistance may enhance survival. Combining epidemiological and clinical studies, this review updates our understanding of HBV-ACLF's definition, diagnosis, epidemiology, etiology, therapy, and prognosis.

Low liver reserve is a risk factor for acute pancreatitis in patients with acute liver failure.

AIM: Acute pancreatitis is a complication of acute liver failure (ALF). This study aimed to investigate the prevalence of and clinical features associated with acute pancreatitis in patients with ALF. METHODS: We retrospectively analyzed a cohort of ALF patients without hepatic encephalopathy diagnosed during a period 2011-2018, and compared clinical features between patients with acute pancreatitis and those without. Acute pancreatitis was diagnosed according to the Acute Pancreatitis Clinical Practice Guidelines 2021. A multivariate analysis was carried out to identify factors associated with acute pancreatitis. RESULTS: There were 83 ALF patients without hepatic encephalopathy (34 men; 11 deaths; 6 liver transplants; median age, 63 years). Acute pancreatitis occurred in nine patients (10.8%). The median time duration from ALF to the onset of acute pancreatitis was 8 days. The survival rate was lower in patients with than those without acute pancreatitis (22% vs. 86%). The model for end-stage liver disease score (hazard ratio 1.10, 95% confidence interval 1.03-1.18) was found to be a significant factor associated with acute pancreatitis, whereas triglyceride, age, and sex were not. CONCLUSIONS: A high model for end-stage liver disease score may be a marker to stratify patients with ALF at a risk of acute pancreatitis.

Comprehensive Treatment of Total Arch Replacement in a Patient With Liver Cirrhosis: A Case Report.

A 78-year-old woman with liver cirrhosis due to chronic hepatitis C visited our department for treatment of a thoracic aortic aneurysm. Her Child-Pugh classification was class A, and her model for end-stage liver (MELD) disease score was 8. As she also had thrombocytopenia associated with splenomegaly and esophageal varices, endoscopic injection sclerotherapy and partial splenic embolization were performed before total arch replacement surgery for treating esophageal varices to reduce the bleeding risk during transesophageal echocardiography and for thrombocytopenia, respectively. After endoscopic injection sclerotherapy and partial splenic embolization, the platelet count increased; hence, total arch replacement surgery was performed. By combining partial splenic embolization and endoscopic injection sclerotherapy, we were able to safely perform transesophageal echocardiography and total arch replacement surgery in the perioperative period.

MELD3.0 is superior to MELDNa and MELD for prediction of mortality in patients with cirrhosis: An external validation in a multi-ethnic population.

Background and Aim: The model for end-stage liver disease (MELD) was updated to MELDNa and recently to MELD3.0 to predict survival of cirrhotic patients. We validated the prognostic performance of MELD3.0 and compared with MELDNa and MELD amongst cirrhotic inpatients. Methods: Demographical, clinical, biochemical, and survival data of cirrhotic inpatients in Singapore General Hospital (SGH) from 01 January 2018 to 31 December 2018, were studied retrospectively. Patients were followed up from first admission in 2018 until death or until 01 April 2023. Area under the receiver operating characteristic curves (AUROC) were computed for the discriminative effects of MELD3.0, MELDNa, and MELD to predict 30-, 90-, and 365-day mortalities. AUROC was compared with DeLong's test. The cutoff MELD3.0 score for patients at high risk of 30-day mortality was determined using Youden's Index. Survival curves of patients with MELD3.0 score above and below the cutoff were estimated with Kaplan-Meier method and compared with log-rank analysis. Results: Totally 862 patients were included (median age 71.0 years [interquartile range, IQR: 64.0-79.0], 65.4% males, 75.8% Chinese). Proportion of patients with Child-Turcotte-Pugh classes A/B/C were 55.5%/35.5%/9.0%. Median MELD3.0/MELDNa/MELD scores were 12.2 (IQR: 8.7-18.3)/11.0 (IQR: 8.0-17.5)/10.3 (IQR: 7.8-15.0). Median time of follow-up was 51.9 months (IQR: 8.5-59.6). The proportion of 30-/90-/365-day mortalities was 5.7%/13.2%/26.9%. AUROC of MELD3.0/MELDNa/MELD in predicting 30-, 90-, and 365-day mortalities, respectively, were 0.823/0.793/0.783, 0.754/0.724/0.707, 0.682/0.654/0.644 (P < 0.05). Optimal cutoff to predict 30-day mortality was MELD3.0 > 19 (sensitivity = 67.4%, specificity = 82.4%). Patients with MELD3.0 > 19, compared with patients with MELD3.0 ≤ 19, had shorter median time to death (98.0 days [IQR: 28.8-398.0] vs 390.0 days [IQR: 134.3-927.5]), and higher proportion of 30-day mortality (68.8% vs 43.0%) (P < 0.001). Conclusion: MELD3.0 performs better than MELDNa and MELD in predicting mortality in cirrhotic inpatients. MELD3.0 > 19 predicts higher 30-day mortality.

A novel scoring system to predict short-term mortality after living donor liver transplantation for acute liver failure.

Liver transplantation is often the only lifesaving option for acute liver failure (ALF); however, the predictors of short-term mortality (death within one year) after living donor liver transplantation (LDLT) for ALF have yet to be defined. We retrospectively collected patients ≥18 years old who underwent LDLT for ALF between 2010 and 2020 at 35 centers in Asia. Univariate and multivariate logistic regression analyses were conducted to identify the clinical variables related to short-term mortality and establish a novel scoring system. The Kaplan-Meier method was performed to explore the association between the score and overall survival. Of the 339 recipients, 46 (13.6%) died within 1 year after LDLT. Multivariate analyses revealed 4 independent risk factors for death: use of vasopressors or mechanical ventilation, the higher model for end-stage liver disease score, and a lower graft-to-recipient weight ratio. The internally validated c-statistic of the short-term mortality after transplant (SMT) score derived from these 4 variables was 0.80 (95% confidence interval: 0.74-0.87). The SMT score successfully stratified recipients into low-, intermediate-, and high-risk groups with 1-year overall survival rates of 96%, 80%, and 50%, respectively. In conclusion, our novel SMT score based on 4 predictors will guide ALF recipient and living donor selection.

Direct-Acting Antiviral Therapy for Patients with Chronic Hepatitis C Infection and Decompensated Cirrhosis.

Patients with chronic hepatitis C virus (HCV) infection and decompensated cirrhosis are an important population for antiviral therapy yet under-represented in clinical trials. HCV direct-acting antiviral (DAA) therapies, unlike interferon-containing regimens, can be safely utilized in decompensated patients. Per guidelines from the American Association for the Study of Liver Diseases (AASLD), therapy of choice in HCV and decompensated cirrhosis is sofosbuvir, an HCV polymerase inhibitor, combined with a replication complex inhibitor (NS5A inhibitor) with or without ribavirin. Combination therapy with a HCV protease inhibitor and an NS5A inhibitor is effective in this population but is specifically not recommended in AASLD guidelines due to safety concerns. Important risk factors for further decompensation during DAA therapy are serum albumin < 3.5 g/dL, MELD (Model for End-Stage Liver Disease) score > 14, or HCV genotype 3 infection. Although sustained virologic response (SVR) is achieved less often in patients with decompensated vs compensated cirrhosis, in clinical studies response rates are > 80%. Both Child-Turcotte-Pugh Class at baseline and viral genotype can affect these response rates. Achieving SVR lowers risk of mortality, but to a lesser extent than in individuals with compensated cirrhosis. Likewise, treating patients for HCV infection along with successful treatment for hepatocellular carcinoma improves risks of both liver-related and overall mortality. In fewer than one third of cases, treating transplant-eligible, HCV-infected patients pre-transplant enables their delisting from transplant wait lists.

Recovery of cardiac electrophysiological alterations by heart rate complexity based on multiscale entropy following liver transplantation.

Autonomic nervous dysfunction is a known cardiac sequalae in patients with end-stage liver disease and is associated with a poor prognosis. Heart rate analysis using nonlinear models such as multiscale entropy (MSE) or complexity may identify marked changes in these patients where conventional heart rate variability (HRV) measurements do not. To investigate the application of heart rate complexity (HRC) based on MSE in liver transplantation settings. Thirty adult recipients of elective living donor liver transplantation were enrolled. HRV parameters using conventional HRV analysis and HRC analysis were obtained at the following time points: (1) 1 day before surgery, (2) postoperative day (POD) 7, (3) POD 14, (4) POD 90, and (5) POD 180. Preoperatively, patients with MELD score ≥ 25 had significantly lower HRC compared to patients with lower MELD scores. This difference in HRC disappeared by POD 7 following liver transplantation and subsequent analyses at POD 90 and 180 continued to show no significant difference. Our results indicated a significant negative correlation between HRC based on MSE analysis and liver disease severity preoperatively, which may be more sensitive than conventional linear HRV analysis. HRC in patients with MELD score ≧ 25 improved over time and became comparable to those with MELD < 25 as early as in 7 days.

Acute-on-Chronic Liver Failure: Causes, Clinical Parameters, and Predictors of Mortality.

Objectives This study aimed to identify the causes, clinical characteristics, and 28-day in-hospital mortality predictors in patients with acute-on-chronic liver failure (ACLF). Methods A cross-sectional study enrolled sixty-four patients aged 18-70 years with acute-on-chronic liver failure. The study was conducted at the Gastroenterology Department, Lahore General Hospital. The study classified ACLF according to the criteria of the European Association for the Study of the Liver - Chronic Liver Failure (EASL-CLIF). Patients were followed for 28 days for mortality outcomes. The outcomes between Survivor and Non-survivor groups were compared using the Chi-Square/Fisher's Exact Test for categorical variables and the Mann-Whitney U test for continuous variables. Results In this study, age and duration of chronic liver disease were not significantly different between survivors and non-survivors. The etiology of liver disease and ACLF causes had no impact on 28-day mortality. Non-survivors had lower mean arterial pressure, and higher mortality was linked with lower Glasgow Coma Scale scores, upper gastrointestinal bleeding, and Grade IV hepatic encephalopathy. Significant differences in bilirubin, serum creatinine, urea, and C-reactive protein levels were observed at 28 days. Survival rates were highest with single organ failure (35.94%) and decreased with multiple organ failures. The overall survival rate was 51.56%. Predictive validity for mortality was assessed using the Area Under the Curve (AUC), with Child-Turcotte-Pugh (CTP) at 0.679, Model for End-Stage Liver Disease (MELD) at 0.819, and Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) at 0.771. Conclusion This study concludes that in acute-on-chronic liver failure, factors like age, gender, and disease etiology do not significantly predict 28-day mortality. Key mortality indicators include clinical parameters such as lower Glasgow Coma Scale scores, hepatic encephalopathy Grade IV, and laboratory findings like elevated bilirubin and serum creatinine. The MELD score is the most compelling prognostic tool.

The Free Triiodothyronine, Gamma-Glutamyl Transpeptidase and Spontaneous Bacterial Peritonitis Index: A Novel Model for Predicting 1-Year Mortality in Patients with HBV-Related Hepatic Encephalopathy.

Background and Aims: Hepatic encephalopathy (HE) is characterized by neuropsychiatric manifestations in patients with decompensated cirrhosis (DC) and/or liver failure. This study aimed to investigate the predictive value of thyroid hormone in patients with HE. Methods: Patients with DC and HE were enrolled, and multivariate logistic analysis was conducted to analyze the risk factors for 1-year mortality. Results: Among the 81 patients with HBV-related DC and HE, 9 (11.1%) died within 3 months, and 15 (18.5%) died within the first year. More patients with FT3 < 3.5pmol/L had ascites (33.3% vs 8.9%, P<0.01) and higher model for end-stage liver disease (MELD) (Z=3.669, P<0.01). Additionally, free triiodothyronine (FT3) levels were lower in the non-survivor group (P<0.01). FT3 exhibited a negative correlation with international normalized ratio and MELD (both P<0.05). Multivariate analysis revealed that FT3, gamma-glutamyl transpeptidase (GGT), and spontaneous bacterial peritonitis (SBP) were independent risk factors for 1-year mortality of HE. A new model incorporating FT3, GTT, and SBP demonstrated superiority to MELD based on the AUROC (0.9 and 0.752, P=0.04). Conclusion: Low FT3, but not thyroid-stimulating hormone and free tetraiodothyronine, was identified as an independent risk factor for 1-year mortality in patients with DC and HE. The newly proposed prognostic model, which includes FT3, GTT, and SBP, holds significant predictive value.

Different serum sodium assay, different model for end stage liver disease - sodium scores in patients awaiting liver transplant: A cross-sectional study.

INTRODUCTION AND AIMS: Sodium can be measured with direct or indirect methods; abnormal plasma total protein concentration can impact on sodium measured by indirect ion-selective electrodes (ISE). Serum sodium is an important item to determine the Model for End Stage Liver Disease Sodium (MELD-Na) score, commonly used for liver graft allocation. Patients with cirrhosis usually have hypoproteinemia. The aim of this study was to determine if there was a significant difference between the MELD-Na scores calculated based on the results of two different serum sodium ISE: indirect and direct. METHODS: This was a retrospective study; we included 166 patients that underwent liver transplant assessment, and that had paired (i.e. same date and time) direct and indirect sodium determinations. We calculated the MELD-Na scores with both sodium determinations, and we compared them. RESULTS: There was a significant difference between MELD-Na scores; the mean difference was 0.4±1.3. If MELD-Na score had been determined by the sodium measured by the direct ISE, 69 patients (42%) would have stayed in the same place on the waiting list, 67 patients (40%) would have moved up, and 30 patients (18%) would have moved down. CONCLUSIONS: There was a statistically significant difference between the MELD-Na scores calculated based on the two different sodium concentrations, which would theoretically result in changes in the order of the waiting list. This finding should prompt studies to assess if MELD-Na calculated based on direct methods has a better performance to predict clinically relevant outcomes.

MELD 3.0 in Advanced Chronic Liver Disease.

The MELD (model for end-stage liver disease) 3.0 score was developed to replace the MELD-Na score that is currently used to prioritize liver allocation for cirrhotic patients awaiting liver transplantation in the United States. The MELD 3.0 calculator includes new inputs from patient sex and serum albumin levels and has new weights for serum sodium, bilirubin, international normalized ratio, and creatinine levels. It is expected that use of MELD 3.0 scores will reduce overall waitlist mortality modestly and improve access for female liver transplant candidates. The utility of MELD 3.0 and PELDcre (pediatric end-stage liver disease, creatinine) scores for risk stratification in cirrhotic patients undergoing major abdominal surgery, placement of a transjugular intrahepatic portosystemic shunt, and other interventions requires further study. This article reviews the background of the MELD score and the rationale to create MELD 3.0 as well as potential implications of using this newer risk stratification tool in clinical practice.

[Transplantation for acute-on-chronic liver failure]. / Transplantation beim akut-auf-chronischen Leberversagen.

A review and discussion of the current literature on liver transplantation for acute-on-chronic liver failure (ACLF) was performed. The ACLF represents an acute deterioration of liver function with pre-existing liver disease and is associated with increasing multiorgan failure, depending on the stage. The 28-day mortality ranges to well over 70% in stage 3 and requires rapid intensive medical treatment involving an interdisciplinary team experienced in transplantation medicine. Under optimized conditions, liver transplantation provides long-term survival rates comparable to other indications. Achieving this requires a differentiated donor selection, choosing the appropriate time for transplantation in the context of a dynamic disease course and the use of appropriate surgical techniques.

The positive impact of the COVID 19 pandemic on organ utilisation in liver transplantation.

Background: As the world recovers from the aftermath of devastating waves of an outbreak, the ongoing Coronavirus disease 2019 pandemic has presented a unique perspective to the transplantation community of ''organ utilisation'' in liver transplantation, a poorly defined term and ongoing hurdle in this field. To this end, we report the key metrics of transplantation activity from a high-volume liver transplantation centre in the United Kingdom over the past two years. Methods: Between March 2019 and February 2021, details of donor liver offers received by our centre from National Health Service Blood & Transplant, and of transplantation were reviewed. Differences in the activity before and after the outbreak of the pandemic, including short term post-transplant survival, have been reported. Results: The pandemic year at our centre witnessed a higher utilisation of Donation after Cardiac Death livers (80.4% vs. 58.3%, p = 0.016) with preserved United Kingdom donor liver indices and median donor age (2.12 vs. 2.02, p = 0.638; 55 vs. 57 years, p = 0.541) when compared to the pre-pandemic year. The 1- year patient survival rates for recipients in both the periods were comparable. The pandemic year, that was associated with increased utilisation of Donation after Cardiac Death livers, had an ischaemic cholangiopathy rate of 6%. Conclusions: The pressures imposed by the pandemic led to increased utilisation of specific donor livers to meet patient needs and minimise the risk of death on the waiting list, with apparently preserved early post-transplant survival. Optimum organ utilisation is a balancing act between risk and benefit for the potential recipient, and technologies like machine perfusion may allow surgeons to increase utilisation without compromising patient outcomes.

Corrected QT interval in cirrhosis: A systematic review and meta-analysis.

BACKGROUND: Corrected QT (QTc) interval is prolonged in patients with liver cirrhosis and has been proposed to correlate with the severity of the disease. However, the effects of sex, age, severity, and etiology of cirrhosis on QTc have not been elucidated. At the same time, the role of treatment, acute illness, and liver transplantation (Tx) remains largely unknown. AIM: To determine the mean QTc in patients with cirrhosis, assess whether QTc is prolonged in patients with cirrhosis, and investigate whether QTc is affected by factors such as sex, age, severity, etiology, treatment, acute illness, and liver Tx. METHODS: In the present systematic review and meta-analysis, the searching protocol "{[QTc] OR [QT interval] OR [QT-interval] OR [Q-T syndrome]} AND {[cirrhosis] OR [Child-Pugh] OR [MELD]}" was applied in PubMed, EMBASE, and Google Scholar databases to identify studies that reported QTc in patients with cirrhosis and published after 1998. Seventy-three studies were considered eligible. Data concerning first author, year of publication, type of study, method used, sample size, mean age, female ratio, alcoholic etiology of cirrhosis ratio, Child-Pugh A/B/C ratio, mean model for end-stage liver disease (MELD) score, treatment with ß-blockers, episode of acute gastrointestinal bleeding, formula for QT correction, mean pulse rate, QTc in patients with cirrhosis and controls, and QTc according to etiology of cirrhosis, sex, Child-Pugh stage, MELD score, and liver Tx status (pre-Tx/post-Tx) were retrieved. The Newcastle-Ottawa quality assessment scale appraised the quality of the eligible studies. Effect estimates, expressed as proportions or standardized mean differences, were combined using the random-effects, generic inverse variance method of DerSimonian and Laird. Subgroup, sensitivity analysis, and meta-regressions were applied to assess heterogeneity. The study has been registered in the PROSPERO database (CRD42023416595). RESULTS: QTc combined mean in patients with cirrhosis was 444.8 ms [95% confidence interval (CI): 440.4-449.2; P < 0.001 when compared with the upper normal limit of 440 ms], presenting high heterogeneity (I2 = 97.5%; 95%CI: 97.2%-97.8%); both Egger's and Begg's tests showed non-significance. QTc was elongated in patients with cirrhosis compared with controls (P < 0.001). QTc was longer in patients with Child-Pugh C cirrhosis when compared with Child-Pugh B and A (P < 0.001); Child-Pugh B patients presented longer QTc when compared with Child-Pugh A patients (P = 0.003). The MELD score was higher in patients with cirrhosis with QTc > 440 ms when compared with QTc ≤ 440 ms (P < 0.001). No correlation of QTc with age (P = 0.693), sex (P = 0.753), or etiology (P = 0.418) was detected. ß-blockers shortened QTc (P< 0.001). QTc was prolonged during acute gastrointestinal bleeding (P = 0.020). Tx tended to improve QTc (P < 0.001). No other sources of QTc heterogeneity were revealed. CONCLUSION: QTc is prolonged in cirrhosis independently of sex, age, and etiology but is correlated with severity and affected by ß-blockers and acute gastrointestinal bleeding. QTc is improved after liver Tx.

Prognostic and diagnostic scoring models in acute alcohol-associated hepatitis: A review comparing the performance of different scoring systems.

Alcohol-associated hepatitis (AAH) is a severe form of liver disease caused by alcohol consumption. In the absence of confounding factors, clinical features and laboratory markers are sufficient to diagnose AAH, rule out alternative causes of liver injury and assess disease severity. Due to the elevated mortality of AAH, assessing the prognosis is a radical step in management. The Maddrey discriminant function (MDF) is the first established clinical prognostic score for AAH and was commonly used in the earliest AAH clinical trials. A MDF > 32 indicates a poor prognosis and a potential benefit of initiating corticosteroids. The model for end stage liver disease (MELD) score has been studied for AAH prognostication and new evidence suggests MELD may predict mortality more accurately than MDF. The Lille score is usually combined to MDF or MELD score after corticosteroid initiation and offers the advantage of assessing response to treatment a 4-7 d into the course. Other commonly used scores include the Glasgow Alcoholic Hepatitis Score and the Age Bilirubin international normalized ratio Creatinine model. Clinical AAH correlate adequately with histologic severity scores and leave little indication for liver biopsy in assessing AAH prognosis. AAH presenting as acute on chronic liver failure (ACLF) is so far prognosticated with ACLF-specific scoring systems. New artificial intelligence-generated prognostic models have emerged and are being studied for use in AAH. Acute kidney injury (AKI) is one possible complication of AAH and is significantly associated with increased AAH mortality. Predicting AKI and alcohol relapse are important steps in the management of AAH. The aim of this review is to discuss the performance and limitations of different scoring models for AAH mortality, emphasize the most useful tools in prognostication and review predictors of recurrence.