Treatment Goals for Primary Biliary Cholangitis, an Australian Perspective

Abstract

ABSTRACT Primary biliary cholangitis (PBC) is an autoimmune liver disease that targets the small intrahepatic bile ducts with diagnosis based on elevated serum alkaline phosphatase (ALP) levels and the presence of anti‐mitochondrial antibodies. Untreated, it may run a progressive course to cirrhosis and hepatic decompensation, at which point liver transplantation is the only effective treatment. This review provides discussion of PBC treatment goals in the Australian context. People with PBC often experience a quality of life burden characterized by fatigue and itch. Extra‐hepatic associations may include osteoporosis, Sjögren's syndrome, and thyroid dysfunction. Established baseline risk factors for progression are male gender, young age at onset (< 45 years), ALP > 1.5 × upper limit of normal (ULN), presence of anti‐gp210 antibodies, and significant liver fibrosis at diagnosis. Ursodeoxycholic acid (UDCA) is the mainstay of therapy and improves outcomes including transplant‐free survival. Patients with inadequate response to UDCA (about 40%), disease progression, or bothersome symptoms require additional second‐line (2L) therapy. Second‐line treatments include selective peroxisome proliferator‐associated receptor (PPAR) agonists, obeticholic acid (OCA; subject to precautions), and off‐label use of fenofibrate. In Australia, reimbursement for 2L therapies relies on ALP ≥ 1.67 × ULN or total bilirubin between 1 and 2 × ULN after 1 year of UDCA therapy. Normalization of ALP is an aspirational treatment target with increasing evidence for improved outcomes. Proactive and diligent monitoring of patients with PBC allows personalized selection and early initiation of effective and well‐tolerated 2L therapies with potential for improved outcomes.