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.

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.

Number needed to treat with ursodeoxycholic acid therapy to prevent liver transplantation or death in primary biliary cholangitis.

Objective: The clinical benefit of ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has never been reported in absolute measures. The aim of this study was to assess the number needed to treat (NNT) with UDCA to prevent liver transplantation (LT) or death among patients with PBC.

Methods: The NNT was calculated based on the untreated LT-free survival and HR of UDCA with respect to LT or death as derived from inverse probability of treatment weighting-adjusted Cox proportional hazard analyses within the Global PBC Study Group database.

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.

Cystic Fibrosis-related Liver Disease: Research Challenges and Future Perspectives.

Objectives: Hepatobiliary complications are a leading cause of morbidity and mortality in cystic fibrosis (CF) patients. Knowledge of the underlying pathological aspects and optimal clinical management is, however, sorely lacking.

Methods: We provide a summary of the lectures given by international speakers at the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) monothematic conference on cystic fibrosis-related liver disease (CFLD) held in Paris in January 2016, to discuss the status of our current knowledge of liver disease in CF patients, to define the critical areas that need to be addressed, and to resolve actions to elucidate relevant mechanisms of disease to optimise future therapeutic options.

Expression patterns of nuclear receptors in parenchymal and non-parenchymal mouse liver cells and their modulation in cholestasis.

Nuclear receptors (NR), the largest family of transcription factors, control many physiological and pathological processes. To gain insight into hepatic NR and their potential as therapeutic targets in cholestatis, we determined their expression in individual cell types of the mouse liver in normal and cholestatic conditions. Hepatocytes, cholangiocytes, hepatic stellate cells (HSC), sinusoidal endothelial cells (SEC) and Kupffer cells (KC) were isolated from the liver of mice with acute or chronic cholestasis (i.

Validation of Transient Elastography and Comparison with Spleen Length Measurement for Staging of Fibrosis and Clinical Prognosis in Primary Sclerosing Cholangitis.

Background: Patients with primary sclerosing cholangitis (PSC) develop progressive liver fibrosis and end-stage liver disease. Non-invasive and widely available parameters are urgently needed to assess disease stage and the risk of clinical progression. Transient elastography (TE) has been reported to predict fibrosis stage and disease progression.

Hepatic manifestations of inflammatory bowel diseases.

Inflammatory bowel diseases are associated with various hepatobiliary disorders, reported both in Crohn's disease and ulcerative colitis. They may occur at any moment in the natural course of the disease. The prevalence of liver dysfunction rises from 3% to 50% accordingly to definitions used in different studies.

Portal myofibroblasts connect angiogenesis and fibrosis in liver.

Liver fibrogenesis is a dynamic process including quantitative and qualitative changes of the extracellular matrix, of which the most prominent is the deposition of type I collagen. These changes progressively disrupt normal liver architecture and result in cirrhosis formation. In the fibrotic liver, as in all other fibrotic tissues, the extracellular matrix is produced by cells usually characterized by the de novo expression of alpha-smooth muscle actin and known as myofibroblasts.

The safety and efficacy of nasobiliary drainage in the treatment of refractory cholestatic pruritus: a multicentre European study.

Background: Pruritus is a common symptom associated with cholestatic liver diseases. To date only small single centre case series have suggested efficacy of nasobiliary drainage in relieving cholestatic pruritus.

Aim: To perform a multicentre study to evaluate the safety and efficacy of nasobiliary drainage in cholestatic pruritus.

Liver Steatosis Assessed by Controlled Attenuation Parameter (CAP) Measured with the XL Probe of the FibroScan: A Pilot Study Assessing Diagnostic Accuracy.

To assess liver steatosis, the controlled attenuation parameter (CAP; giving an estimate of ultrasound attenuation ∼3.5 MHz) is available with the M probe of the FibroScan. We report on the adaptation of the CAP for the FibroScan XL probe (center frequency 2.

Preventive administration of UDCA after liver transplantation for primary biliary cirrhosis is associated with a lower risk of disease recurrence.

Background & Aims: Recurrence of primary biliary cirrhosis (PBC) after liver transplantation (LT) is not rare and can occasionally lead to severe graft dysfunction and retransplantation. Ursodeoxycholic acid (UDCA) is a safe and effective treatment for PBC. However, whether preventive administration of UDCA after LT could lower the incidence of PBC recurrence is unknown.

Membranous Nephropathy Associated With Immunological Disorder-Related Liver Disease: A Retrospective Study of 10 Cases.

The association between membranous nephropathy (MN) and immunological disorder-related liver disease has not been extensively investigated, and the specific features of this uncommon association, if any, remain to be determined.We retrospectively identified 10 patients with this association. We aimed to describe the clinical, biological, and pathological characteristics of these patients and their therapeutic management.

Fenofibrate is effective adjunctive therapy in the treatment of primary biliary cirrhosis: A meta-analysis.

Background And Aim: Fenofibrate is a potential novel therapy for primary biliary cirrhosis (PBC). We performed a systematic review and a meta-analysis of studies of fenofibrate in PBC.

Methods: Electronic database search was performed for relevant studies.

Evidence-based treatment of primary biliary cirrhosis.

The natural history of primary biliary cirrhosis (PBC) has improved greatly during the past two decades because of its diagnosis at earlier stages and the widespread use of ursodeoxycholic acid as first-line treatment. As a result, far fewer patients require liver transplantation and patients diagnosed with early-stage disease appear to have a normal life expectancy. The evidence-based treatment of PBC is reviewed here.

Baseline values and changes in liver stiffness measured by transient elastography are associated with severity of fibrosis and outcomes of patients with primary sclerosing cholangitis.

Background & Aims: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease that leads to extensive liver fibrosis and cirrhosis, which are associated with poor outcome. However, there are no validated noninvasive markers of liver fibrosis in patients with PSC. We assessed the diagnostic performance, reproducibility, longitudinal changes, and prognostic value of liver stiffness measurement (LSM) using vibration-controlled transient elastography (VCTE).

Ursodeoxycholic acid and bile-acid mimetics as therapeutic agents for cholestatic liver diseases: an overview of their mechanisms of action.

Chronic cholestasis and liver inflammation are the two main pathophysiological components of the two major classes of disease - primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) - leading to bile duct destruction and ultimately to cirrhosis and liver failure. Ursodeoxycholic acid (UDCA), initially introduced as a therapeutic approach to counteract the cholestatic components to PBC and PSC, was subsequently shown to exhibit unexpected anti-inflammatory and immunomodulatoty properties. The use of farnesoid X receptor (FXR) and TGR5 agonists in various animal models have confirmed early observations indicating that bile acids are not only toxicants and inflammagens, but also repressors of innate and adaptive immunity.

Primary biliary cirrhosis and bile acids.

The dihydroxylated bile acid ursodeoxycholic acid (UDCA) has now been regarded for 20 years as the standard treatment for primary biliary cirrhosis (PBC), a chronic cholestatic immune-mediated condition marked by progressive destruction of small intrahepatic bile ducts, impaired biliary secretion, hepatocellular retention of toxic endogenous bile acids and, ultimately, the development of fibrosis leading to cirrhosis that commonly requires liver transplantation. At first sight, it seems intriguing that a bile acid could be considered for use as a therapeutic agent in a bile-acid secretion disorder. Yet, in addition to its inherently greater hydrophilic nature and competitive effect on endogenous bileacid recycling, UDCA has indeed been demonstrated to be a potent post-transcriptional secretagogue as well as a potential anti-inflammatory and anti-apoptotic agent.

Protoporphyrin retention in hepatocytes and Kupffer cells prevents sclerosing cholangitis in erythropoietic protoporphyria mouse model.

Background & Aims: Chronic, progressive hepatobiliary disease is the most severe complication of erythropoietic protoporphyria (EPP) and can require liver transplantation, although the mechanisms that lead to liver failure are unknown. We characterized protoporphyrin-IX (PPIX)-linked hepatobiliary disease in BALB/c and C57BL/6 (Fechm1Pas) mice with mutations in ferrochelatase as models for EPP.

Methods: Fechm1Pas and wild-type (control) mice were studied at 12-14 weeks of age.