Resolution of MASH with no worsening of fibrosis after bariatric surgery improves 15-year survival: a prospective cohort study.

Objectives: Investigate the consequences of the histological progression of metabolically 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 MASH patients.

O-GlcNAcylation controls pro-fibrotic transcriptional regulatory signaling in myofibroblasts.

Tissue injury causes activation of mesenchymal lineage cells into wound-repairing myofibroblasts (MFs), whose uncontrolled activity ultimately leads to fibrosis. Although this process is triggered by deep metabolic and transcriptional reprogramming, functional links between these two key events are not yet understood. Here, we report that the metabolic sensor post-translational modification O-linked β-D-N-acetylglucosaminylation (O-GlcNAcylation) is increased and required for myofibroblastic activation.

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.

Liver Transplantation in Alcohol-related Liver Disease and Alcohol-related Hepatitis.

Alcohol-related liver disease (ARLD) remains one of the leading causes of chronic liver disease and the prevalence of alcohol-related cirrhosis is still increasing worldwide. Thus, ARLD is one of the leading indications for liver transplantation (LT) worldwide especially after the arrival of direct-acting antivirals for chronic hepatitis C infection. Despite the risk of alcohol relapse, the outcomes of LT for ARLD are as good as for other indications such as hepatocellular carcinoma (HCC), with 1-, 5-, and 10- year survival rates of 85%, 74%, and 59%, respectively.

Functional genomics uncovers the transcription factor BNC2 as required for myofibroblastic activation in fibrosis.

Tissue injury triggers activation of mesenchymal lineage cells into wound-repairing myofibroblasts, whose unrestrained activity leads to fibrosis. Although this process is largely controlled at the transcriptional level, whether the main transcription factors involved have all been identified has remained elusive. Here, we report multi-omics analyses unraveling Basonuclin 2 (BNC2) as a myofibroblast identity transcription factor.

Benefits of tailored hepatocellular carcinoma screening in patients with cirrhosis on cancer-specific and overall mortality: A modeling approach.

To validate cancer screening programs, experts recommend estimating effects on case fatality rates (CFRs) and cancer-specific mortality. This study evaluates hepatocellular carcinoma (HCC) screening in patients with cirrhosis for those outcomes using a modeling approach. We designed a Markov model to assess 10-year HCC-CFR, HCC-related, and overall mortality per 100,000 screened patients with compensated cirrhosis.

Management of alcohol-related liver disease: the French Association for the Study of the Liver and the French Alcohol Society clinical guidelines.

Excessive alcohol consumption is the leading cause of liver diseases in Western countries, especially in France. Alcohol-related liver disease (ARLD) is an extremely broad context and there remains much to accomplish in terms of identifying patients, improving prognosis and treatment, and standardising practices. The French Association for the Study of the Liver wished to organise guidelines together with the French Alcohol Society in order to summarise the best evidence available about several key clinical points in ARLD.

Morbid obesity increases death and dropout from the liver transplantation waiting list: A prospective cohort study.

Unlabelled: Liver transplant (LT) candidates with a body mass index (BMI) over 40 kg/m have lower access to a liver graft without clear explanation. Thus, we studied the impact of obesity on the waiting list (WL) and aimed to explore graft proposals and refusal.

Method: Data between January 2007 and December 2017 were extracted from the French prospective national database: CRISTAL.

Lung Infection Affects Access to Treatment and Short-Term Outcome in Patients With Severe Alcohol-Related Hepatitis Treated With Corticosteroids.

Introduction: Severe alcohol-related hepatitis (AH) is associated with an increased risk of infection, but the impact of pneumonia has not been specifically analyzed in a specific cohort.

Methods: All patients admitted for severe AH between 2002 and 2020 were prospectively included. Systematic screening for infection was performed at admission and renewed in the case of clinical suspicion.

Loss of hepatocyte identity following aberrant YAP activation: A key mechanism in alcoholic hepatitis.

Background & Aims: Alcoholic hepatitis (AH) is a life-threatening disease with limited therapeutic options, as the molecular mechanisms leading to death are not well understood. This study evaluates the Hippo/Yes-associated protein (YAP) pathway which has been shown to play a role in liver regeneration.

Method: The Hippo/YAP pathway was dissected in explants of patients transplanted for AH or alcohol-related cirrhosis and in control livers, using RNA-seq, real-time PCR, western blot, immunohistochemistry and transcriptome analysis after laser microdissection.

Acute Liver Injury With Therapeutic Doses of Acetaminophen: A Prospective Study.

Background And Aims: Because of the extensive use of this drug, further evaluation of acute liver injury (ALI) with therapeutic doses of acetaminophen (APAP; ≤6 g/d) is required. We characterize ALI with therapeutic doses of APAP and determine the host factors associated with disease severity and the predictors of outcome.

Approach And Results: All patients admitted with severe APAP-related ALI in our center were included from 2002 to 2019, either attributable to therapeutic doses or overdose.

Consequences of TIPSS placement on the body composition of patients with cirrhosis and severe portal hypertension: a large retrospective CT-based surveillance.

Background: Body composition may be modified after improvement of portal hypertension (PHT) by transjugular intrahepatic portosystemic shunt (TIPSS) insertion.

Aims: To evaluate changes in body composition following TIPSS placement, their relationship with radiological TIPSS patency and function, and the predictive value of these parameters METHODS: We retrospectively included 179 patients with cirrhosis who underwent TIPSS placement in our centre for severe PHT from 2011 to 2017. CT scan-based surveillance was performed at baseline, 1-3 (M1-M3) and 6 months (M6).

A tool to predict progression of non-alcoholic fatty liver disease in severely obese patients.

Background & Aims: Severely obese patients are a growing population at risk of non-alcoholic fatty liver disease (NAFLD). Considering the increasing burden, a predictive tool of NAFLD progression would be of interest. Our objective was to provide a tool allowing general practitioners to identify and refer the patients most at risk, and specialists to estimate disease progression and adapt the therapeutic strategy.

Bariatric Surgery Provides Long-term Resolution of Nonalcoholic Steatohepatitis and Regression of Fibrosis.

Background And Aims: Studies are needed to determine the long-term effects of bariatric surgery for patients with nonalcoholic steatohepatitis (NASH). We evaluated sequential liver samples, collected the time of bariatric surgery and 1 and 5 years later, to assess the long-term effects of bariatric surgery in patients with NASH.

Methods: We performed a prospective study of 180 severely obese patients with biopsy-proven NASH, defined by the NASH clinical research network histologic scores.

Combined alcoholic and non-alcoholic steatohepatitis.

While metabolic syndrome and alcohol consumption are the two main causes of chronic liver disease, one of the two conditions is often predominant, with the other acting as a cofactor of morbimortality. It has been shown that obesity and alcohol act synergistically to increase the risk of fibrosis progression, hepatic carcinogenesis and mortality, while genetic polymorphisms can strongly influence disease progression. Based on common pathogenic pathways, there are several potential targets that could be used to treat both diseases; based on the prevalence and incidence of these diseases, new therapies and clinical trials are needed urgently.

IL-33/ST2 pathway regulates neutrophil migration and predicts outcome in patients with severe alcoholic hepatitis.

Background & Aims: Severe alcoholic hepatitis (SAH) is associated with a high risk of infection. The IL-33/ST2 pathway is involved in sepsis control but data regarding its role in alcohol-related liver disease (ALD) are lacking. We aimed to characterize the role of IL-33/ST2 in the polymorphonuclear neutrophils (PMNs) of patients with ALD and SAH.

A Model to Identify Heavy Drinkers at High Risk for Liver Disease Progression.

Background & Aims: Alcohol-related liver disease (ALD) causes chronic liver disease. We investigated how information on patients' drinking history and amount, stage of liver disease, and demographic feature can be used to determine risk of disease progression.

Methods: We collected data from 2334 heavy drinkers (50 g/day or more) with persistently abnormal results from liver tests who had been admitted to a hepato-gastroenterology unit in France from January 1982 through December 1997; patients with a recorded duration of alcohol abuse were assigned to the development cohort (n=1599; 75% men) or the validation cohort (n=735; 75% men), based on presence of a liver biopsy.

[What is the position of bariatric surgery in the treatment of non-alcoholic steatohepatitis?].

Bariatric surgery is indicated for patients with BMI≥35kg/m and associated steatohepatitis. Bariatric surgery induces NASH disappearance for nearly 80% of patients after 1 year of follow up. Bariatric surgery is associated with low morbidity and mortality if patients are well selected.