{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:13:41Z","timestamp":1787170421341,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T00:00:00Z","timestamp":1576022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aim<\/jats:title>\n                    <jats:p>Primary biliary cholangitis (PBC) patients who are refractory to ursodeoxycholic acid (UDCA) are at risk for progression to cirrhosis and liver failure. Bezafibrate could be an alternative second\u2010line therapeutic option in these patients. This study aimed to evaluate the long\u2010term outcome(s) of combined UDCA and bezafibrate therapy in UDCA\u2010refractory PBC patients and identify prognostic factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Among 445 patients treated with UDCA, 150 patients inadequately responded to UDCA monotherapy and received long\u2010term UDCA plus bezafibrate (median, 15\u00a0years). Data from these patients were used for this retrospective analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Combination therapy resulted in significant improvements in serum biochemistry and liver transplantation risk estimated using the UK\u2010PBC\u2010risk and the GLOBE scores. The cumulative normalization rates of alkaline phosphatase, gamma\u2010glutamyltransferase, and immunoglobulin M (IgM) were significantly higher in patients without cirrhosis\u2010related symptoms or liver\u2010related events than in those with them. Overall, IgM constantly emerged as a significant factor associated with cirrhosis\u2010related symptoms and liver\u2010related events at all time points. Cumulative survival rates were significantly lower in patients with IgM\u00a0\u2265\u00a0240\u00a0mg\/dL than in patients with IgM\u00a0&lt;\u00a0240\u00a0mg\/dL. Thus, normalization of IgM levels was a good surrogate predictor of long\u2010term prognosis. None of the patients discontinued combination therapy due to any adverse events during the follow\u2010up period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings point to the beneficial effects of long\u2010term UDCA plus bezafibrate combination therapy for UDCA\u2010refractory PBC patients, and IgM response can be a useful predictive biomarker of long\u2010term clinical outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jgh.14900","type":"journal-article","created":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T22:06:56Z","timestamp":1572646016000},"page":"663-672","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["IgM response is a prognostic biomarker of primary biliary cholangitis treated with ursodeoxycholic acid and bezafibrate"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3134-4888","authenticated-orcid":false,"given":"Keiko","family":"Takano","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7407-6142","authenticated-orcid":false,"given":"Chisato","family":"Saeki","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1365-5391","authenticated-orcid":false,"given":"Tsunekazu","family":"Oikawa","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine The Jikei 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