Liver Transplantation for Primary Sclerosing Cholangitis (PSC) With or Without Inflammatory Bowel Disease (IBD)-A European Society of Organ Transplantation (ESOT) Consensus Statement.

Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD) and a lead indication for liver transplantation (LT) in the western world. In this article, we present a Consensus Statement on LT practice, developed by a dedicated Guidelines' Taskforce of the European Society of Organ Transplantation (ESOT). The overarching goal is to provide practical guidance on commonly debated topics, including indications and timing of LT, management of bile duct stenosis in patients on the transplant waiting list, technical aspects of transplantation, immunosuppressive strategies post-transplant, timing and extension of intestinal resection and futility criteria for re-transplantation.

Autoimmune hepatitis recurrence after liver transplantation: "Les jeux sont faits".

Autoimmune hepatitis (AIH) may recur after liver transplantation (LT). The aims of this study were to evaluate the incidence and risk factors for recurrent autoimmune hepatitis (rAIH). A multicenter retrospective French nationwide study, including all patients aged ≥16 transplanted for AIH, with at least 1 liver biopsy 1 year after LT, was conducted between 1985 and 2018.

Long-term outcome of liver transplantation for autoimmune hepatitis: A French nationwide study over 30 years.

Background & Aims: Autoimmune hepatitis (AIH) is a rare indication for liver transplantation (LT). The aims of this study were to evaluate long-term survival after LT for AIH and prognostic factors, especially the impact of recurrent AIH (rAIH).

Methods: A multicentre retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted.

Ivacaftor-Mediated Potentiation of ABCB4 Missense Mutations Affecting Critical Motifs of the NBDs: Repositioning Perspectives for Hepatobiliary Diseases.

ABCB4 (ATP-binding cassette subfamily B member 4) is a hepatocanalicular floppase involved in biliary phosphatidylcholine (PC) secretion. Variations in the ABCB4 gene give rise to several biliary diseases, including progressive familial intrahepatic cholestasis type 3 (PFIC3), an autosomal recessive disease that can be lethal in the absence of liver transplantation. In this study, we investigated the effect and potential rescue of ten ABCB4 missense variations in NBD1:NBD2 homologous positions (Y403H/Y1043H, K435M/K1075M, E558K/E1200A, D564G/D1206G and H589Y/H1231Y) all localized at the conserved and functionally critical motifs of ABC transporters, six of which are mutated in patients.

Liver transplantation for autoimmune hepatitis: Pre-transplant does not predict the early post-transplant outcome.

Background And Aims: Autoimmune hepatitis (AIH) is a rare indication (<5%) for liver transplantation (LT). The aim of this study was to describe the early outcome after LT for AIH.

Methods: A multicenter retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted.

RIPK3 dampens mitochondrial bioenergetics and lipid droplet dynamics in metabolic liver disease.

Background And Aims: Receptor-interacting protein kinase 3 (RIPK3) mediates NAFLD progression, but its metabolic function is unclear. Here, we aimed to investigate the role of RIPK3 in modulating mitochondria function, coupled with lipid droplet (LD) architecture in NAFLD.

Approach And Results: Functional studies evaluating mitochondria and LD biology were performed in wild-type (WT) and Ripk3-/- mice fed a choline-deficient, amino acid-defined (CDAA) diet for 32 and 66 weeks and in CRISPR-Cas9 Ripk3 -null fat-loaded immortalized hepatocytes.

MRCK-Alpha and Its Effector Myosin II Regulatory Light Chain Bind ABCB4 and Regulate Its Membrane Expression.

ABCB4, is an adenosine triphosphate-binding cassette (ABC) transporter localized at the canalicular membrane of hepatocytes, where it mediates phosphatidylcholine secretion into bile. Gene variations of ABCB4 cause different types of liver diseases, including progressive familial intrahepatic cholestasis type 3 (PFIC3). The molecular mechanisms underlying the trafficking of ABCB4 to and from the canalicular membrane are still unknown.

Machine learning in primary biliary cholangitis: A novel approach for risk stratification.

Background & Aims: Machine learning (ML) provides new approaches for prognostication through the identification of novel subgroups of patients. We explored whether ML could support disease sub-phenotyping and risk stratification in primary biliary cholangitis (PBC).

Methods: ML was applied to an international dataset of PBC patients.

A systemic mechanism of increased transendothelial migration of leukocytes through the blood-brain barrier in hepatic encephalopathy.

Background: Hepatic encephalopathy (HE) is a frequent neurological complication of cirrhosis. Evidence suggests a synergic pathophysiological implication of hyperammonemia and systemic inflammation. In addition, the blood-brain barrier (BBB) permeability can be impaired in cirrhotic patients, notably in those displaying HE.

Non-invasive diagnosis and follow-up of autoimmune hepatitis.

Autoimmune hepatitis (AIH) is a liver disease characterised by necrotico-inflammatory lesions of hepatocytes, the presence of specific autoantibodies and response to corticosteroid treatment. AIH must be considered in any patient with acute or chronic liver disease. As there is no pathognomonic sign of AIH, the diagnosis is based on a combination of clinical, biological, immunological and histological findings, after excluding other causes of liver disease.

Early liver transplantation for corticosteroid non-responders with acute severe autoimmune hepatitis: The SURFASA score.

Background & Aims: In acute severe autoimmune hepatitis (AS-AIH), the optimal timing for liver transplantation (LT) remains controversial. The objectives of this study were to determine early predictive factors for a non-response to corticosteroids and to propose a score to identify patients in whom LT is urgently indicated.

Methods: This was a retrospective, multicenter study (2009-2016).

Cold-Atmospheric Plasma Induces Tumor Cell Death in Preclinical In Vivo and In Vitro Models of Human Cholangiocarcinoma.

Through the last decade, cold atmospheric plasma (CAP) has emerged as an innovative therapeutic option for cancer treatment. Recently, we have set up a potentially safe atmospheric pressure plasma jet device that displays antitumoral properties in a preclinical model of cholangiocarcinoma (CCA), a rare and very aggressive cancer emerging from the biliary tree with few efficient treatments. In the present study, we aimed at deciphering the molecular mechanisms underlying the antitumor effects of CAP towards CCA in both an in vivo and in vitro context.

Genetic contribution of ABCC2 to Dubin-Johnson syndrome and inherited cholestatic disorders.

Background And Aims: The ABCC2 gene is implicated in Dubin-Johnson syndrome (DJS), a rare autosomal recessive liver disorder. The primary aim of this study was to determine the diagnostic value of ABCC2 genetic testing in the largest cohort of DJS reported to date. The high number of patients with cholestatic manifestations in this series prompted us to evaluate the genetic contribution of rare, potentially pathogenic ABCC2 variants to other inherited cholestatic disorders.

Expanding the mutational spectrum of the ABCB4 gene in inherited adult cholestatic liver disorders with four novel pathogenic variants.

Low phospholipid-associated cholelithiasis and intrahepatic cholestasis of pregnancy are two MDR3-related inherited liver disorders caused by biallelic or monoallelic ABCB4 loss-of-function variants. Low phospholipid-associated cholelithiasis is clinically characterized by the early onset of symptomatic cholelithiasis in young adults while intrahepatic cholestasis of pregnancy is a distinct clinical entity associated with adverse fetal outcomes. Of note, patients carrying ABCB4 sequence variations commonly exhibit phenotypic expression over a wide continuum due to environmental and hormonal contributing factors and genetic modifiers.