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Clinical Gastroenterology and... Jul 2023Primary biliary cholangitis (PBC) is an archetypal autoimmune disease. Chronic lymphocytic cholangitis is associated with interface hepatitis, ductopenia, cholestasis,... (Review)
Review
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.
Topics: Humans; Female; Male; Liver Cirrhosis, Biliary; Quality of Life; Peroxisome Proliferator-Activated Receptors; Ursodeoxycholic Acid; Cholangitis; Cholestasis; Pruritus
PubMed: 36809835
DOI: 10.1016/j.cgh.2023.02.005 -
Hepatology Communications Jun 2023Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune liver disease characterized by a destructive, small duct, and lymphocytic cholangitis, and marked...
Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune liver disease characterized by a destructive, small duct, and lymphocytic cholangitis, and marked by the presence of antimitochondrial antibodies. The incidence and prevalence of PBC vary widely in different regions and time periods, and although disproportionally more common among White non-Hispanic females, contemporary data show a higher prevalence in males and racial minorities than previously described. Outcomes largely depend on early recognition of the disease and prompt institution of treatment, which, in turn, are directly influenced by provider bias and socioeconomic factors. Ursodeoxycholic acid remains the initial treatment of choice for PBC, with obeticholic acid and fibrates (off-label therapy) reserved as add-on therapy for the management of inadequate responders or those with ursodeoxycholic acid intolerance. Novel and repurposed drugs are currently at different stages of clinical development not only for the treatment of PBC but also for its symptomatic management. Here, we summarize the most up-to-date data regarding the epidemiology, prognosis, and treatment of PBC, providing clinically useful information for its holistic management.
Topics: Male; Female; Humans; Ursodeoxycholic Acid; Liver Cirrhosis, Biliary; Cholangitis; Prognosis; Cholestasis
PubMed: 37267215
DOI: 10.1097/HC9.0000000000000179