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Early diagnosis of PBC is crucial to mitigate the onset of advanced liver disease. However, even after diagnosis, some patients with PBC remain untreated or continue to progress to advanced disease despite initiation of treatment. Further, extrahepatic symptoms such as pruritus and fatigue substantially affect quality of life yet may not be addressed with standard treatment. Ursodeoxycholic acid (UDCA) stands as the first-line treatment for PBC and has been shown to increase survival and reduce the need for liver transplantation. Nonetheless, some patients have an inadequate response or are intolerant to UDCA. Furthermore, UDCA does not address pruritus or fatigue. Approved second-line therapies for PBC include elafibranor and seladelpar. Elafibranor and seladelpar were recently granted Food and Drug Administration (FDA) approval in the accelerated pathway after reducing alkaline phosphatase (ALP) levels and showing promise in improving patient-reported symptoms such as pruritus and fatigue, though they are not without adverse events. With the availability of these new, second-line therapies, current treatment guidelines should be updated to emphasize early evaluation of treatment response to UDCA and to incorporate patient-reported outcomes that impact symptom burden and quality of life. With the\u00a0current emphasis on patient engagement and personalized medicine, clinicians should consider evaluating symptom burden at diagnosis and improving quality of life to be as important as ALP levels in terms of successful PBC treatment.<\/jats:p>","DOI":"10.1007\/s10620-025-09537-3","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T13:18:14Z","timestamp":1763731094000},"page":"1640-1649","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Optimizing Care in Primary Biliary Cholangitis: Current Treatments and the Second-Line Decision"],"prefix":"10.1007","volume":"71","author":[{"given":"Gina","family":"Choi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun B.","family":"Jesudian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sammy","family":"Saab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"9537_CR1","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1016\/S0140-6736(20)31607-X","volume":"396","author":"A Lleo","year":"2020","unstructured":"Lleo A, Wang G-Q, Gershwin ME, Hirschfield GM. 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