{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:56:26Z","timestamp":1788173786502,"version":"build-2803163510"},"reference-count":67,"publisher":"The Korean Association for the Study of the Liver","issue":"1","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"funder":[{"name":"GSK"},{"DOI":"10.13039\/100015993","name":"Kowa Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015993","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["e-cmh.org"],"crossmark-restriction":true},"short-container-title":["Clin Mol Hepatol"],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:p>Patients with hard-to-treat autoimmune hepatitis (AIH) or primary biliary cholangitis (PBC) are defined a posteriori as those who do not show a sufficient response or are intolerant to pharmacological treatments, thus not achieving biochemical surrogate endpoints that are associated with long-term liver-related-event-free survival. The absence of a recently harmonized definition of \u2018complete biochemical response within 6 months (CBR\u22646M)\u2019, which is defined as the normalization of serum transaminase and IgG levels below the upper limit of normal at \u22646 months after treatment initiation, is regarded as hard-to-treat AIH. The implementation of CBR\u22646M, in turn, has been facilitating clinical trials, e.g., between azathioprine and mycophenolate mofetil, to reconsider appropriate first-line steroid sparing agents, leading to a reduction in the number of hard-to-treat AIH cases. Regarding PBC, one of the disseminated definitions of hard-to-treat patients is the absence of POISE criteria, which are evaluated at 12 months with serum alkaline phosphatase and bilirubin levels, after the introduction of ursodeoxycholic acid. Hard-to-treat PBC not meeting the POISE criteria has very recently been the target population for the U.S. FDA-approved second-line drugs, elafibranor and seladelpar. In future pharmacological treatment of AIH and PBC, the primary objective for AIH is likely to focus on lowering the number of hard-to-treat patients with personalized steroid sparing treatment regimens. A challenging goal in PBC treatment is the further optimization of treatment surrogate endpoints, even to the stricter alkaline phosphatase normalization, with which an indication of second- or later-line drugs might be expanded, but could ultimately lengthen patients\u2019 long-term survival.<\/jats:p>","DOI":"10.3350\/cmh.2024.0821","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T07:37:33Z","timestamp":1731310653000},"page":"90-104","update-policy":"https:\/\/doi.org\/10.3350\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Hard-to-treat autoimmune hepatitis and primary biliary cholangitis: The dawn of a new era of pharmacological treatment"],"prefix":"10.3350","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2607-9381","authenticated-orcid":true,"given":"Atsumasa","family":"Komori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kugiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1902","reference":[{"key":"ref1","first-page":"1543","volume-title":"EASL clinical practice guidelines: autoimmune hepatitis. 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