A comprehensive review of systemic sclerosis-primary biliary cholangitis overlap: emerging evidence for a distinct clinical subtype.

Purpose Of Review: To synthesize current knowledge on the genetic, immunopathogenic, and clinical presentations of systemic sclerosis (SSc) and primary biliary cholangitis (PBC) with a focus on their co-occurrence as a clinically relevant overlap syndrome. This narrative review summarizes preclinical and clinical studies addressing SSc-PBC overlap.

Recent Findings: Genomic studies highlight shared susceptibility loci between SSc and PBC.

Determining Best Practices and Content for Foundational Ambulatory GI and Hepatology Teaching During GI Fellowship.

Less than 10% of adult gastroenterology (GI) fellowship is required to occur in the ambulatory, office-based, setting according to the Accreditation Council for Graduate Medical Education (ACGME). However, most GI fellowship graduates will spend a significant portion of their career in this setting. Training programs outside of GI have utilized multiple interventions to help bridge this educational training gap between inpatient-heavy training and outpatient-focused practice.

Hepatotoxicity of Chemotherapy and Immune Checkpoint Inhibitors.

Hepatotoxicity from oncologic drugs represents an increasing clinical burden for patients, providers, and the health care system. The complexity of clinical presentations, multi-drug regimens, and the need to control the underlying cancer while preserving liver function, results in significant diagnostic and therapeutic challenges. These challenges are best met with a careful and systematic approach with multi-disciplinary management decisions between oncology and hepatology providers.

Treatment of pruritus in primary sclerosing cholangitis: Analysis of the consortium for autoimmune liver disease registry.

Background: Cholestasis from primary sclerosing cholangitis (PSC) frequently causes pruritus. However, the prevalence of pruritus and its management have not been well studied. Investigating the Cholestatic Pruritus of Primary Sclerosing Cholangitis (ItCh-PSC) includes a retrospective medical record review to determine the prevalence, severity, and treatment patterns of pruritus.

Hepatic Encephalopathy and MELD-Na Predict Treatment Benefit in Autoimmune Hepatitis-related Decompensated Cirrhosis.

Background & Aims: Management of patients with autoimmune hepatitis (AIH)-related decompensated cirrhosis is challenging because of the risk of treatment-related complications and lack of clinical recommendations. We investigated the predictive factors for treatment benefit in AIH-related decompensated cirrhosis at diagnosis and developed an algorithm to guide treatment decisions in clinical practice.

Methods: This retrospective, international, multicenter study included 232 patients with histologically confirmed AIH-related decompensated cirrhosis at diagnosis.

autoimmune hepatitis? - Summary of the 5 international autoimmune hepatitis group research workshop 2024.

Autoimmune hepatitis (AIH) is a rare chronic liver disease with an increasing incidence in many countries. Chronic autoimmune responses against the liver can cause hepatic and extrahepatic symptoms, decreased quality of life and reduced liver transplant-free survival if inadequately treated. Although standard treatment with corticosteroids and thiopurines improves the life expectancy of patients with AIH, remission rates and tolerability are generally overestimated and the development of alternative first-line and salvage therapies has been disappointingly slow compared to in rheumatological diseases or inflammatory bowel disease.

Pathophysiology of Cystic Fibrosis Liver Disease.

Hepatobiliary complications of Cystic Fibrosis (CF) constitute a significant burden for persons with CF of all ages, with advanced CF liver disease in particular representing a leading cause of mortality. The causes of the heterogeneity of clinical manifestations, ranging from steatosis to focal biliary cholestasis and biliary strictures, are poorly understood and likely reflect a variety of environmental and disease-modifying factors in the setting of underlying CFTR mutations. This review summarizes the current understanding of the pathophysiology of hepatobiliary manifestations of CF, and discusses emerging disease models and therapeutic approaches that hold promise to impact this important yet incompletely addressed aspect of CF care.

Autoimmune hepatitis: Brighton Collaboration case definition and guidelines for data collection, analysis, and presentation of immunisation safety data.

This report introduces a Brighton Collaboration (BC) case definition for autoimmune hepatitis (AIH), which has been classified as a priority adverse event of special interest (AESI), as there were possible cases seen following COVID-19 vaccination. The case definition was developed by a group of subject matter and BC process experts to facilitate safety data comparability across pre- and post-licensure clinical trials, as well as pharmacovigilance activities in multiple settings with diverse resources and healthcare access. The usual BC case definition development process was followed in an expedited manner, and took two months to complete, including finalising the manuscript for publication, instead of the usual 1 year development time.

African American race does not confer an increased risk of clinical events in patients with primary sclerosing cholangitis.

Background: The natural history of primary sclerosing cholangitis (PSC) among African Americans (AA) is not well understood.

Methods: Transplant-free survival and hepatic decompensation-free survival were assessed using a retrospective research registry from 16 centers throughout North America. Patients with PSC alive without liver transplantation after 2008 were included.

Cystic fibrosis screening, evaluation, and management of hepatobiliary disease consensus recommendations.

Cystic fibrosis (CF) may cause a spectrum of hepatobiliary complications, including portal hypertension, multilobular cirrhosis, and liver failure. Current guidelines on the detection and monitoring of hepatobiliary complications in CF were published in 1999. The CF Foundation assembled a committee to evaluate research advances and formulate revised guidelines for CF-associated liver disease.

Advancing diagnosis and management of liver disease in adults through exome sequencing.

Background: Whole-exome sequencing (WES) is an effective tool for diagnosis in patients who remain undiagnosed despite a comprehensive clinical work-up. While WES is being used increasingly in pediatrics and oncology, it remains underutilized in non-oncological adult medicine, including in patients with liver disease, in part based on the faulty premise that adults are unlikely to harbor rare genetic variants with large effect size. Here, we aim to assess the burden of rare genetic variants underlying liver disease in adults at two major tertiary referral academic medical centers.

Research gaps and opportunities in autoimmune hepatitis-Results of the international autoimmune hepatitis group research workshop 2022.

Autoimmune hepatitis (AIH) is a rare autoimmune liver disease that is characterised by a chronic inflammatory immune reaction directed against hepatocytes. The disease results in a substantial reduction in quality of life and potentially leads to liver-related complications or death. The International Autoimmune Hepatitis Group (IAIHG) initiated a series of research workshops to uncover the scientific gaps and opportunities in AIH.

Unique DUOX2ACE2 small cholangiocytes are pathogenic targets for primary biliary cholangitis.

Cholangiocytes play a crucial role in bile formation. Cholangiocyte injury causes cholestasis, including primary biliary cholangitis (PBC). However, the etiology of PBC remains unclear despite being characterized as an autoimmune disease.

Outcomes of immunomodulator and advanced therapies for primary sclerosing cholangitis-associated inflammatory bowel disease.

Background: Inflammatory bowel disease (IBD) coexists in up to 80% of patients with primary sclerosing cholangitis (PSC). The aim of this study is to investigate the outcomes of immunomodulator (IMM)/advanced therapies for the treatment of PSC-IBD.

Methods: This was a single-center, retrospective study of patients with PSC from 1 January 2012 to 1 April 2021.

Update in Advancing the Gastrointestinal Frontier in Cystic Fibrosis.

Clinical complications of cystic fibrosis (CF) include a variety of gastrointestinal (GI) and hepatobiliary manifestations. Recent years have witnessed several advances in the understanding and management of these complications, in addition to opportunities for therapeutic innovations. Herein we review the current understanding of these disorders and also discuss the management of the GI and hepatobiliary complications experienced by persons with CF.

Fenofibrate Downregulates NF-κB Signaling to Inhibit Pro-inflammatory Cytokine Secretion in Human THP-1 Macrophages and During Primary Biliary Cholangitis.

Chronic liver diseases, e.g., cholestasis, are negatively impacted by inflammation, which further aggravates liver injury.

Noninvasive biomarkers for the diagnosis and management of autoimmune hepatitis.

Autoimmune hepatitis (AIH) is a rare disease of unclear etiology characterized by loss of self-tolerance that can lead to liver injury, cirrhosis, and acute liver failure. First-line treatment consists of systemic corticosteroids, or budesonide, and azathioprine, to which most patients are initially responsive, although predictors of response are lacking. Relapses are very common, correlate with histological activity despite normal serum transaminases, and increase hepatic fibrosis.