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.

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.

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.

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.

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.

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.

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.

[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.