Primary biliary cholangitis (PBC) is an archetypal autoimmune disease. Chronic lymphocytic cholangitis is associated with interface hepatitis, ductopenia, cholestasis, and progressive biliary fibrosis. People living with PBC are frequently symptomatic, experiencing a quality-of-life burden dominated by fatigue, itch, abdominal pain, and sicca complex. Although the female predominance, specific serum autoantibodies, immune-mediated cellular injury, as well as genetic (HLA and non-HLA) risk factors, identify PBC as autoimmune, to date treatment has focused on cholestatic consequences. Biliary epithelial homeostasis is abnormal and contributes to disease. The impact of cholangiocyte senescence, apoptosis, and impaired bicarbonate secretion enhances chronic inflammation and bile acid retention. First-line therapy is a non-specific anti-cholestatic agent, ursodeoxycholic acid. For those with residual cholestasis biochemically, obeticholic acid is introduced, and this semisynthetic farnesoid X receptor agonist adds choleretic, anti-fibrotic, and anti-inflammatory activity. Future PBC licensed therapy will likely include peroxisome proliferator activated receptor (PPAR) pathway agonists, including specific PPAR-delta agonism (seladelpar), as well as elafibrinor and saroglitazar (both with broader PPAR agonism). These agents dovetail the clinical and trial experience for off-label bezafibrate and fenofibrate use. Symptom management is essential, and encouragingly, PPAR agonists reduce itch; IBAT inhibition (eg, linerixibat) also appears promising for pruritus. For those where liver fibrosis is the target, NOX inhibition is being evaluated. Earlier stage therapies in development include therapy to impact immunoregulation in patients, as well other approaches to treating pruritus (eg, antagonists of MrgprX4). Collectively the PBC therapeutic landscape is exciting. Therapy goals are increasingly proactive and individualized and aspire to rapidly achieve normal serum tests and quality of life with prevention of end-stage liver disease.
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http://dx.doi.org/10.1016/j.cgh.2023.02.005 | DOI Listing |
Pharmacoepidemiol Drug Saf
January 2025
Hunan Institute for Drug Control, Changsha, Hunan, China.
Background And Objectives: Based on the Adverse Event Reporting System (FAERS) data from the US FDA, this study mined the adverse drug reactions of obeticholic acid (OCA) in the real world and provided reference for clinical safe drug use.
Methods: Adverse event reports for OCA from the second quarter of 2016 to the third quarter of 2023 were extracted. The analysis for adverse reaction signal detection was conducted using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods.
Chirurgie (Heidelb)
January 2025
Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Deutschland.
Multimorbidity is characterized by the presence of at least 3 chronic diseases with a prevalence of more than 50% of patients over 60 years old. The Charlson comorbidity index (CCI) enables a description of the severity of the multimorbidity and also provides a correlation with the postoperative outcome after liver resection. According to this, multimorbid patients are at increased risk of morbidity and mortality after liver resection, mostly due to postoperative liver failure.
View Article and Find Full Text PDFHepatology
January 2025
Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy.
Primary Biliary Cholangitis (PBC) is a chronic cholestatic liver disease characterized by the progressive destruction of intrahepatic bile ducts, leading to fibrosis, and potentially cirrhosis. PBC has been considered a prototypical autoimmune condition, given the presence of specific autoantibodies and the immune response against well-defined mitochondrial autoantigens. Further evidence supports the interaction of immunogenetic and environmental factors in the aetiology of PBC.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
College of Environmental Science and Engineering, Yangzhou University, Yangzhou 225127, China.
Primary biliary cholangitis (PBC) is a chronic disease, the prevalence of which has been increasing in recent years. And the prevalence of patients who test negative with existing diagnostic techniques remains high. It was found that the antigenic BCOADC-E2 protein could detect patients with a negative original test.
View Article and Find Full Text PDFJ Clin Med
December 2024
Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA.
The integration of artificial intelligence (AI) into hepatology is revolutionizing the diagnosis and management of liver diseases amidst a rising global burden of conditions like metabolic-associated steatotic liver disease (MASLD). AI harnesses vast datasets and complex algorithms to enhance clinical decision making and patient outcomes. AI's applications in hepatology span a variety of conditions, including autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, MASLD, hepatitis B, and hepatocellular carcinoma.
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