{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T18:41:16Z","timestamp":1789065676082,"version":"build-2803163510"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T00:00:00Z","timestamp":1555027200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,4,12]],"date-time":"2019-04-12T00:00:00Z","timestamp":1555027200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:p>In Japan, bezafibrate (BF) is a second\u2010line agent for primary biliary cholangitis (PBC) that is refractory to ursodeoxycholic acid (UDCA) treatment. From a retrospective cohort (n = 873) from the Japan PBC Study Group, we enrolled 118 patients who had received UDCA monotherapy for at least 1 year followed by combination therapy with UDCA+BF for at least 1 year. GLOBE and UK\u2010PBC scores after UDCA monotherapy (i.e., immediately before UDCA+BF combination therapy) were compared with those after 1 year of UDCA+BF combination therapy. The real outcomes of enrolled patients estimated by Kaplan\u2013Meier analysis were compared with the predicted outcomes calculated using GLOBE and UK\u2010PBC scores. In addition, the hazard ratio of BF treatment was calculated using propensity score analysis. The mean GLOBE score before the combination therapy was 0.504 \u00b1 0.080, which improved significantly to 0.115 \u00b1 0.085 (<jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 0.0001) after 1 year of combination therapy. The real liver transplant\u2010free survival of enrolled patients was significantly better than that predicted by GLOBE score before introducing BF. Combination therapy did not significantly improve the real rates of liver transplantation or liver\u2010related death compared with those predicted by UK\u2010PBC risk score before introducing BF, but the predicted risk was significantly reduced by the addition of BF (<jats:italic toggle=\"yes\">P <\/jats:italic>&lt; 0.0001). Cox regression analysis with inverse probability of treatment weighting showed that the addition of BF significantly reduced the hazard of liver transplant or liver\u2010related death in patients who, after 1 year of UDCA monotherapy, had normal serum bilirubin (adjusted hazard ratio 0.09, 95% confidence interval 0.01\u20100.60, <jats:italic toggle=\"yes\">P <\/jats:italic>= 0.013). <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Addition of BF to UDCA monotherapy improves not only GLOBE and UK\u2010PBC scores but also the long\u2010term prognosis of PBC patients, especially those with early\u2010stage PBC.<\/jats:p>","DOI":"10.1002\/hep.30552","type":"journal-article","created":{"date-parts":[[2019,2,9]],"date-time":"2019-02-09T04:10:56Z","timestamp":1549685456000},"page":"2035-2046","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":112,"title":["Bezafibrate Improves GLOBE and UK\u2010PBC Scores and Long\u2010Term Outcomes in Patients With Primary Biliary Cholangitis"],"prefix":"10.1097","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0902-8272","authenticated-orcid":false,"given":"Akira","family":"Honda","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine,Tokyo Medical University Ibaraki Medical Center,Ibaraki,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Medicine,Teikyo University School of Medicine,Tokyo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuji","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Teikyo Academic Research Center,Teikyo University,Tokyo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsumasa","family":"Komori","sequence":"additional","affiliation":[{"name":"Clinical Research Center,National Hospital Organization (NHO) Nagasaki Medical Center,Nagasaki,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology,Ehime University Graduate School of Medicine,Ehime,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mie","family":"Inao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Medicine,Saitama Medical University,Saitama,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Namisaki","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine,Nara Medical University,Nara,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoaki","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Tokyo Teishin Hospital,Tokyo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhito","family":"Kawata","sequence":"additional","affiliation":[{"name":"Hepatology Division, Department of Internal Medicine,Hamamatsu University School of Medicine,Hamamatsu,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Fukushima Medical University School of Medicine,Fukushima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Ninomiya","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology,Tohoku University Graduate School of Medicine,Sendai,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong\u2010Hon","family":"Kang","sequence":"additional","affiliation":[{"name":"Center for Gastroenterology,Teine Keijinkai Hospital,Sapporo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mie","family":"Arakawa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Faculty of Medicine,Oita University,Yufu City,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Yamagiwa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Niigata University Graduate School of Medical and Dental Sciences,Niigata,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Joshita","sequence":"additional","affiliation":[{"name":"Division of Hepatology and Gastroenterology, Department of Medicine,Shinshu University School of Medicine,Matsumoto,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7985-919X","authenticated-orcid":false,"given":"Takeji","family":"Umemura","sequence":"additional","affiliation":[{"name":"Division of Hepatology and Gastroenterology, Department of Medicine,Shinshu University School of Medicine,Matsumoto,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Gunma University Graduate School of Medicine,Maebashi,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,NTT West Osaka Hospital,Osaka,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"The Fourth Department of Internal Medicine,Teikyo University Mizonokuchi Hospital,Kanagawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Itakura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Musashino Red Cross Hospital,Tokyo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Nomura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Neurology,Kagawa University School of Medicine,Kagawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9627-138X","authenticated-orcid":false,"given":"Keisuke","family":"Kakisaka","sequence":"additional","affiliation":[{"name":"Division of Hepatology, Department of Internal Medicine,Iwate Medical University,Morioka,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Hepatology, Graduate School of Medicine,Osaka City University,Osaka,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norifumi","family":"Kawada","sequence":"additional","affiliation":[{"name":"Department of Hepatology, Graduate School of Medicine,Osaka City University,Osaka,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Takikawa","sequence":"additional","affiliation":[{"name":"Division of Hepatology, Department of Internal Medicine,Iwate Medical University,Morioka,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Masaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Neurology,Kagawa University School of Medicine,Kagawa,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromasa","family":"Ohira","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Fukushima Medical University School of Medicine,Fukushima,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Mochida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Medicine,Saitama Medical University,Saitama,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Yoshiji","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine,Nara Medical University,Nara,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Iimuro","sequence":"additional","affiliation":[{"name":"Teikyo Academic Research Center,Teikyo University,Tokyo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Matsuzaki","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine,Tokyo Medical University Ibaraki Medical 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