Targeted inhibition of pathobiont virulence factor mitigates alcohol-associated liver disease.

Alcohol-associated liver disease poses a global health burden with high mortality. Imbalances in the gut microbiota are important for disease progression. Using metagenomic sequencing of fecal samples from a multicenter, international cohort of patients with alcohol-associated hepatitis, we found that the presence of virulence factor KpsM, encoded in the genome of Escherichia coli (E.

An Expert Consensus Delphi Panel in Metabolic Dysfunction- and Alcohol-associated Liver Disease: Opportunities and Challenges in Clinical Practice.

Background & Aims: Metabolic dysfunction- and alcohol-associated liver disease (MetALD) is a recently defined entity for individuals with liver steatosis, metabolic dysfunction, and increased alcohol intake. However, the current definition of MetALD poses multiple challenges in clinical practice and research. In this Delphi consensus, we provide practical recommendations for the clinical assessment and management of MetALD to address current clinical challenges in MetALD.

How Secondary Interventions Reduce the Burden of Alcohol Consumption at Risk of Cirrhosis: A Public Health Decision-Making Model.

Background: Better understanding of the kinetics of the consumption of alcohol at risk of cirrhosis (≥ 20 g/day) and the prediction of the burden of alcohol consumption are needed for public health decision-making.

Methods: Based on individual data from 45 054 individuals, collected from the French Health, Health Care and Insurance Survey between 2002 and 2014, a Markov model was developed to predict the future burden of alcohol consumption ≥ 20 g/day. This estimated the incidence of alcohol intake with an intermediate (20-50 g/day) or high (≥ 50 g/day) risk of cirrhosis.

Value of non-invasive test dynamics in guiding HCC surveillance decisions after HCV cure in patients with cirrhosis.

Background & Aims: Whether the dynamics of non-invasive tests (NITs) correlate with hepatocellular carcinoma (HCC) risk in patients with cirrhosis following sustained virological response (SVR) remains unknown. Thus, we aimed to describe NIT dynamics and assess their correlation with HCC risk.

Methods: The dynamics of NITs (fibrosis-4 index [FIB-4], aspartate aminotransferase-to-platelet ratio index [APRI] and liver stiffness measurement) were described in patients with cirrhosis after SVR included in two prospective French multicenter cohorts (ANRS CO22 Hepather and CO12 CirVir) between 2006 and 2015.

Global epidemiology of alcohol-related liver disease, liver cancer, and alcohol use disorder, 2000-2021.

Background/aims: Alcohol represents a leading burden of disease worldwide, including alcohol use disorder (AUD) and alcohol-related liver disease (ALD). We aim to assess the global burden of AUD, ALD, and alcohol-attributable primary liver cancer between 2000-2021.

Methods: We registered the global and regional trends of AUD, ALD, and alcohol-related liver cancer using data from the Global Burden of Disease 2021 Study, the largest and most up-to-date global epidemiology database.

Resolution of Metabolic Dysfunction-associated Steatohepatitis With No Worsening of Fibrosis After Bariatric Surgery Improves 15-year Survival: A Prospective Cohort Study.

Background & Aims: The aim of this study was to investigate the consequences of the histological progression of metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis on long-term survival after bariatric surgery.

Methods: From 1994 to 2021, 3028 patients at the University Hospital of Lille were prospectively included. Baseline liver biopsies were systematically performed with proposed follow-up biopsies 1 year after surgery, mainly in patients with MASH.

Metabolic dysfunction and alcohol-related liver disease (MetALD): Position statement by an expert panel on alcohol-related liver disease.

In this position statement, we explore the intricate relationship between alcohol intake and metabolic dysfunction in the context of the 2023 nomenclature update for steatotic liver disease (SLD). Recent and lifetime alcohol use should be accurately assessed in all patients with SLD to facilitate classification of alcohol use in grams of alcohol per week. Alcohol biomarkers (i.

Direct Antivirals Can Achieve a Cure in All Patients With Chronic Hepatitis C due to Genotype 5: A French Multicentre Study.

Background: Hepatitis C virus genotype 5 (HCV-GT-5) is found mainly in South Africa. In our area in central France, the prevalence of HCV-GT-5 is 14%.

Methods And Results: Here we evaluated sustained virological response at week 12 post-treatment (SVR12) in 147 HCV-GT-5 patients from 14 French university hospitals (2014-2021) treated with direct-acting antivirals (DAA) in real-life.

Socioeconomic Deprivation Weighs Heavily on Liver Fibrosis and Mortality After Hepatitis C Cure (ANRS CO22 Hepather).

Although Hepatitis C virus (HCV) infection can be cured with direct-acting antivirals (DAA), some cured patients face a serious risk of advanced liver damage and early mortality. In order to avoid these two negative health outcomes, it is important to identify and assess related risk factors. Little is currently known about socioeconomic and behavioural factors in this context.

Alcohol Rehabilitation Within 3 Months After Alcohol Hepatitis and Survival: A National Analysis.

Background & Aims: There is limited understanding of the benefits of alcohol rehabilitation after alcohol hepatitis (AH).

Methods: We conducted a 2012 to 2021 national longitudinal study involving adult inpatients diagnosed with AH in France. We assessed the primary outcome of liver transplantation or death within 1 year after AH, including in its complicated form (CAH) defined as ≥2 hepatic or extrahepatic complications within 4 weeks after AH.

Relationship between updated MELD and prognosis in alcohol-associated hepatitis: Opportunities for more efficient trial design.

Background: Alcohol-associated hepatitis (AH) is associated with significant mortality. Model for End-Stage Liver Disease (MELD) score is used to predict short-term mortality and aid in treatment decisions. MELD is frequently updated in the course of AH.

Treatment with bulevirtide in HIV-infected patients with chronic hepatitis D: ANRS HD EP01 BuleDelta and compassionate cohort.

Background & Aims: In France, bulevirtide (BLV) became available in September 2019 through an early access program to treat patients with HDV. The aim of this analysis was to evaluate the efficacy and safety of BLV in patients with HIV and HDV coinfection.

Methods: Patients received BLV 2 mg ± pegylated interferon-α (pegIFNα) according to the physician's decision.

Faecal proteomics links neutrophil degranulation with mortality in patients with alcohol-associated hepatitis.

Objective: Patients with alcohol-associated hepatitis (AH) have a high mortality. Alcohol exacerbates liver damage by inducing gut dysbiosis, bacterial translocation and inflammation, which is characterised by increased numbers of circulating and hepatic neutrophils.

Design: In this study, we performed tandem mass tag (TMT) proteomics to analyse proteins in the faeces of controls (n=19), patients with alcohol-use disorder (AUD; n=20) and AH (n=80) from a multicentre cohort (InTeam).

Long-term outcome following liver transplantation of patients with ACLF grade 3.

Background & Aims: Utility, a major principle for allocation in the context of transplantation, is questioned in patients with acute-on-chronic liver failure grade 3 (ACLF-3) who undergo liver transplantation (LT). We aimed to explore long-term outcomes of patients included in a three-centre retrospective French study published in 2017.

Method: All patients with ACLF-3 (n = 73), as well as their transplanted matched controls with ACLF-2 (n = 145), 1 (n = 119) and no ACLF (n = 292), who participated in the Princeps study published in 2017 were included.

A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry.

Background: Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We developed a PRS for alcohol-associated cirrhosis by comparing single-nucleotide polymorphisms among patients with alcohol-associated cirrhosis (ALC) versus drinkers who did not have evidence of liver fibrosis/cirrhosis.

Methods: Using a data-driven approach, a PRS for ALC was generated using a meta-genome-wide association study of ALC (N=4305) and an independent cohort of heavy drinkers with ALC and without significant liver disease (N=3037).

Early prediction of the impact of public health policies on obesity and lifetime risk of type 2 diabetes: A modelling approach.

Objective: Help public health decision-making requires a better understanding of the dynamics of obesity and type 2 diabetes and an assessement of different strategies to decrease their burdens.

Methods: Based on 97,848 individual data, collected in the French Health, Health Care and Insurance Survey over 1998-2014, a Markov model was developed to describe the progression of being overweight to obesity, and the onset of type 2 diabetes. This model traces and predicts 2022-2027 burdens of obesity and type 2 diabetes, and lifetime risk of diabetes, according to different scenarios aiming at minimum to stabilize obesity at 5 years.

Serum aryl hydrocarbon receptor activity is associated with survival in patients with alcohol-associated hepatitis.

Background And Aims: Patients with alcohol-associated hepatitis (AH) have an altered fecal metabolome, including reduced microbiota-derived tryptophan metabolites, which function as ligands for aryl hydrocarbon receptor (AhR). The aim of this study was to assess serum AhR ligand activity in patients with AH.

Approach And Results: The study included 74 controls without AUD, 97 patients with AUD, and 330 patients with AH from 2 different multicenter cohorts (InTeam: 134, AlcHepNet: 196).

Performance of non-invasive tests for liver fibrosis resolution after bariatric surgery.

Background & Aims: The value of non-invasive tests for monitoring the resolution of significant liver fibrosis after treatment is poorly investigated. We compared the performances of six non-invasive tests to predict the resolution of significant fibrosis after bariatric surgery.

Methods: Participants were individuals with obesity submitted to needle liver biopsy at the time of bariatric surgery, and 12 and/or 60 months after surgery.

Time-of-day-dependent variation of the human liver transcriptome and metabolome is disrupted in MASLD.

Background & Aims: Liver homeostasis is ensured in part by time-of-day-dependent processes, many of them being paced by the molecular circadian clock. Liver functions are compromised in metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), and clock disruption increases susceptibility to MASLD progression in rodent models. We therefore investigated whether the time-of-day-dependent transcriptome and metabolome are significantly altered in human steatotic and MASH livers.