Defining Risk in Alcohol-Associated Liver Disease Using the Model for End-Stage Liver Disease.

Introduction: Alcohol-associated liver disease (ALD) is a common cause of morbidity and premature mortality. Most prognostic scores have been defined in the short term. We used a large retrospective cohort of patients with ALD to describe the natural history of ALD and to define risk prediction in the longer term, taking nonliver mortality into account.

Diabetes mellitus in alcohol-associated liver disease: Prevalence and outcomes.

Background: Alcohol associated liver disease (ALD) is a common condition that is a significant global cause of morbidity and mortality. Diabetes mellitus (DM) increases the risk of adverse outcomes in other types of steatotic liver disease. This retrospective study sought to explore the relationship between ALD and DM.

Conserved Sequence Identification Within Large Genomic Datasets Using 'Unikseq2': Application in Environmental DNA Assay Development.

Identification of conserved genomic sequences and their utilisation as anchor points for clade detection and/or characterisation is a mainstay in ecological studies. For environmental DNA (eDNA) assays, effective processing of large genomic datasets is crucial for reliable species detection in biodiversity monitoring. While considerable focus has been on developing robust species-targeted assays, eDNA assays with broader taxonomic coverage (e.

Motivation, self-efficacy, and identity-double-edged swords for relapse prevention in patients with alcohol related cirrhosis.

Background And Aims: Despite the critical importance of alcohol abstinence for patients with advanced liver disease, rates of returning to alcohol remain high and engagement with relapse prevention interventions is low. This study explores the potential barriers to relapse prevention in these patients.

Methods: Semi-structured interviews were conducted with patients who had alcohol-related cirrhosis or alcohol-associated hepatitis.

Incidence and predictors of non-hepatic cancers in biopsy-proven alcohol-related liver disease.

Introduction And Objectives: Alcohol-related liver disease (ALD) is a known contributor to non-hepatic cancers (NHC). We aimed to describe the incidence and predictors of NHC in patients with ALD.

Materials And Methods: The WALDO study is a multicenter cohort study of patients with histologically characterized ALD.

Women and People From Deprived Areas Are Less Likely to be Assessed for Liver Transplantation for Alcohol-related Liver Disease: Results From a National Study of Transplant Assessments.

Background: Alcohol-related liver disease (ArLD) is the most common indication for liver transplantation in Europe and the United States. Few studies have examined the characteristics of patients with ArLD formally assessed for liver transplants.

Methods: We collected prospective data on every patient with ArLD formally assessed for liver transplantation in the United Kingdom during a 12-mo period.

Severe Cholestasis Predicts Recurrent Primary Sclerosing Cholangitis Following Liver Transplantation.

Introduction: Primary sclerosing cholangitis (PSC) may reoccur following liver transplantation (LT), and the diagnosis established once imaging studies demonstrate the diagnostic cholangiographic appearance. To evaluate whether the development of recurrent PSC (rPSC) is associated with cholestasis soon after LT, we studied whether changes in hepatic biochemistry within the first 12 months were linked with the development of rPSC and graft loss.

Methods: We conducted a retrospective cohort analysis of 158 transplant recipients with PSC in Canada and 549 PSC transplant recipients from the United Kingdom.

Oxidised Apolipoprotein Peptidome Characterises Metabolic Dysfunction-Associated Steatotic Liver Disease.

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) encompasses a spectrum of histological conditions ranging from simple steatosis to fibrosing steatohepatitis, and is a risk factor for cardiovascular diseases (CVD). While oxidised apolipoproteins A and B have been linked to obesity and CVD, the association between other oxidised apolipoproteins and MASLD is yet to be established. To fill this gap, we characterised the circulating serum peptidome of patients with MASLD.

Real-world analysis of acamprosate use in patients with cirrhosis and alcohol-associated hepatitis.

Objective: Preventing return to alcohol is of critical importance for patients with alcohol-related cirrhosis and/or alcohol-associated hepatitis. Acamprosate is a widely used treatment for alcohol use disorder (AUD). We assessed the impact of acamprosate prescription in patients with advanced liver disease on abstinence rates and clinical outcomes.

Liver transplantation for critically ill patients with acute on chronic liver failure: a prospective national programme of waitlist prioritisation.

Background: Acute on Chronic Liver Failure (ACLF) complicates chronic liver disease (CLD) combining rapidly progressive hepatic with extra-hepatic multiple organ failure and high short-term mortality. Effective therapeutic options are very limited, and liver transplantation (LT) seldom utilised through concerns of high recipient mortality and resource use. Retrospective reports suggest recent outcomes may have improved, but use of LT for ACLF has not been prospectively assessed.

Type of calcineurin inhibitor and long-term outcomes following liver transplantation in patients with primary biliary cholangitis - an ELTR study.

Background & Aims: Tacrolimus has been associated with recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT), which in turn may reduce survival. This study aimed to assess the association between the type of calcineurin inhibitor used and long-term outcomes following LT in patients with PBC.

Methods: Survival analyses were used to assess the association between immunosuppressive drugs and graft or patient survival among adult patients with PBC in the European Liver Transplant Registry.

Effects of storage conditions on the stability of qPCR reagents: implications for environmental DNA detection.

Objective: Environmental DNA (eDNA) detection is a transformative tool for ecological surveys which in many cases offers greater accuracy and cost-effectiveness for tracking low-density, cryptic species compared to conventional methods. For the use of targeted quantitative PCR (qPCR)-based eDNA detection, protocols typically require freshly prepared reagents for each sample, necessitating systematic evaluation of reagent stability within the functional context of eDNA standard curve preparation and environmental sample evaluation. Herein, we assessed the effects of long-term storage and freeze-thaw cycles on qPCR reagents for eDNA analysis across six assays.

An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, encompasses steatosis and metabolic dysfunction-associated steatohepatitis (MASH), leading to cirrhosis and hepatocellular carcinoma. Preclinical MASLD research is mainly performed in rodents; however, the model that best recapitulates human disease is yet to be defined. We conducted a wide-ranging retrospective review (metabolic phenotype, liver histopathology, transcriptome benchmarked against humans) of murine models (mostly male) and ranked them using an unbiased MASLD 'human proximity score' to define their metabolic relevance and ability to induce MASH-fibrosis.

Acquisition of epithelial plasticity in human chronic liver disease.

For many adult human organs, tissue regeneration during chronic disease remains a controversial subject. Regenerative processes are easily observed in animal models, and their underlying mechanisms are becoming well characterized, but technical challenges and ethical aspects are limiting the validation of these results in humans. We decided to address this difficulty with respect to the liver.

Diet and physical activity interventions to improve cardiovascular disease risk factors in liver transplant recipients: Systematic review and meta-analysis.

Background And Aims: Cardiovascular disease, associated risk factors and obesity are prevalent after liver transplant and modifiable through lifestyle changes. Understanding what lifestyle interventions and their respective components are effective is essential for translation to clinical practice. We aimed to investigate the effects of diet and physical activity interventions on weight, body mass index and other cardiovascular disease risk factors in liver transplant recipients, and systematically describe the interventions.

The clinical value of the hepatic venous pressure gradient in patients undergoing hepatic resection for hepatocellular carcinoma with or without liver cirrhosis.

The role of hepatic venous pressure gradient (HVPG) measurement in risk stratification before liver resection is an ongoing area of debate. This study examines the impact of preoperative HVPG levels on overall survival (OS)/time to recurrence (TTR) and postoperative complications after hepatic resection of hepatocellular carcinoma (HCC). Thirty-eight HCC patients undergoing HVPG measurement before liver resection at Cambridge University Hospitals NHS Foundation Trust between January 2014 and April 2022 were retrospectively analysed.

Machine learning approaches to enhance diagnosis and staging of patients with MASLD using routinely available clinical information.

Aims: Metabolic dysfunction Associated Steatotic Liver Disease (MASLD) outcomes such as MASH (metabolic dysfunction associated steatohepatitis), fibrosis and cirrhosis are ordinarily determined by resource-intensive and invasive biopsies. We aim to show that routine clinical tests offer sufficient information to predict these endpoints.

Methods: Using the LITMUS Metacohort derived from the European NAFLD Registry, the largest MASLD dataset in Europe, we create three combinations of features which vary in degree of procurement including a 19-variable feature set that are attained through a routine clinical appointment or blood test.

Localized Liver Injury During Normothermic Ex Situ Liver Perfusion Has No Impact on Short-term Liver Transplant Outcomes.

Background: Normothermic ex situ liver perfusion (NESLiP) has the potential to increase organ utilization. Radiological evidence of localized liver injury due to compression at the time of NESLiP, termed cradle compression, is a recognized phenomenon but is poorly characterized.

Methods: A retrospective analysis of a prospectively collected database was performed of transplanted livers that underwent NESLiP and subsequently had a computed tomography performed within the first 14 d posttransplant.

Recent outcomes of liver transplantation for Budd-Chiari syndrome: A study of the European Liver Transplant Registry (ELTR) and affiliated centers.

Background And Aims: Management of Budd-Chiari syndrome (BCS) has improved over the last decades. The main aim was to evaluate the contemporary post-liver transplant (post-LT) outcomes in Europe.

Approach And Results: Data from all patients who underwent transplantation from 1976 to 2020 was obtained from the European Liver Transplant Registry (ELTR).

Health-related Quality of Life in Patients With Nonalcoholic Fatty Liver Disease: A Prospective Multi-center UK Study.

Background & Aims: It is unclear whether health-related quality of life (HRQoL) is impaired in patients with nonalcoholic fatty liver disease (NAFLD) without advanced fibrosis and how this compares with the general population. We aimed to assess HRQoL in patients with NAFLD in comparison to the general population and any associations of fibrosis severity and metabolic comorbidities with impairments in HRQoL.

Methods: We prospectively enrolled 513 consecutive patients with NAFLD who completed the EuroQol 5-dimensional questionnaire (EQ-5D) and Chronic Liver Disease Questionnaires (CLDQ).

Modelling TDP-43 proteinopathy in Drosophila uncovers shared and neuron-specific targets across ALS and FTD relevant circuits.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) comprise a spectrum of neurodegenerative diseases linked to TDP-43 proteinopathy, which at the cellular level, is characterized by loss of nuclear TDP-43 and accumulation of cytoplasmic TDP-43 inclusions that ultimately cause RNA processing defects including dysregulation of splicing, mRNA transport and translation. Complementing our previous work in motor neurons, here we report a novel model of TDP-43 proteinopathy based on overexpression of TDP-43 in a subset of Drosophila Kenyon cells of the mushroom body (MB), a circuit with structural characteristics reminiscent of vertebrate cortical networks. This model recapitulates several aspects of dementia-relevant pathological features including age-dependent neuronal loss, nuclear depletion and cytoplasmic accumulation of TDP-43, and behavioral deficits in working memory and sleep that occur prior to axonal degeneration.

Routine Extubation in the Operating Room After Isolated Coronary Artery Bypass.

Background: The benefits of fast-track extubation in the intensive care unit (ICU) after cardiac surgery are well established. Although extubation in the operating room (OR) is safe in carefully selected patients, widespread use of this strategy in cardiac surgery remains unproven. This study was designed to evaluate perioperative outcomes with OR vs ICU extubation in patients undergoing nonemergency, isolated coronary artery bypass grafting (CABG).

Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol.

Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic.