336 research outputs found
Autoimmune liver disease: evaluating overlapping and cross-over presentations—a case-based discussion
The three classic autoimmune liver diseases are recognised based on identifying varying clinical, laboratory, histological and radiological features that collectively classify patients. In the absence of defined aetiological factors, it is recognised that disease spectrum is broad, and, in this context, it is not infrequent for disease boundaries to be blurred, leading to overlapping features that may be present at the time of diagnosis or may appear later in the course of disease. Given the absence of accepted diagnostic criteria for overlap/cross-over syndromes, alongside weak data for intervention, it is recommended that a multidisciplinary, patient-specific approach be used to establish individual treatment pathways
The pathogenesis of autoimmune liver disease
<b><i>Background:</i></b> Autoimmune liver disease (AILD) encompasses 3 main distinct clinical diseases: autoimmune hepatitis, primary biliary cholangitis (formally known as cirrhosis, PBC) and primary sclerosing cholangitis (PSC). These conditions are an important, yet under-appreciated cause of patient morbidity and mortality with ongoing unmet needs for further research and clinical advances. <b><i>Key Messages:</i></b> There is observational evidence for genetic predisposition, with all 3 conditions being more common in first degree relatives. AILD is associated with the presence of auto-antibodies and higher risks of other non-hepatic auto-immune conditions. Genetic risk association studies have identified HLA and non-HLA risk loci for the development of disease, with some HLA loci providing prognostic information. This re-enforces the concept that genetic predisposition to autoimmunity is important, likely in the context of environmental exposures. Such environmental triggers are unclear but relevant risks include smoking, drug and xenobiotic exposure as well as the complexities of the microbiome. There is evidence for a loss of immune tolerance to self-antigens playing a part in the development of these conditions. In particular the IL-2 and IL-12 regulatory pathways have been implicated in pre-disposing to an unopposed inflammatory response within the liver. Main immunological themes revolve around loss of immune tolerance leading to T-cell mediated injury, imbalance in the regulation of immune cells and defective immune response to foreign antigens. For PBC and PSC, there is then the added complexity of the consequences of cholestasis on hepato-biliary injury, immune regulation and liver fibrosis. <b><i>Conclusions:</i></b> Whilst specific disease causes and triggers are still lacking, AILD arises on the background of collective genetic and environmental risk, leading to chronic and abnormal hepato-biliary immune responses. Effective and more rational therapy will ultimately be developed when the multiple pathways to liver injury are better understood.</jats:p
Primary sclerosing cholangitis and overlap features of autoimmune hepatitis:A coming of age or an age-ist problem?
Apical Sodium-Dependent Transporter Inhibitors in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis
Bile acids (BAs) have gained mainstream attention since the discovery of their key role as signalling molecules in health and disease. The apical sodium-dependent transporter (ASBT) protein located in the terminal ileum plays an important physiological role in the enterohepatic circulation of BAs and therefore essential for the BA homeostasis. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), the 2 most common cholestatic liver diseases are characterised by altered BA flow and BA composition, which contribute to disease progression and symptom (pruritus) development. Therefore, changing the circulating BA pool in patients with PBC and PSC may have therapeutic implications. To this end, pharmacological inhibition of ASBT is fast emerging as an interesting target. In this review, we discuss the recent evidence for potential therapeutic use of ASBT inhibitors to treat PBC and PSC patients.</jats:p
Reply to: “AST/platelet ratio index associates with progression to hepatic failure and correlates with histological fibrosis stage in Japanese patients with primary biliary cirrhosis”
Barriers to implementation of stratified care in Primary Biliary Cholangitis:a scoping exercise
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