Bezafibrate Improves GLOBE and UK-PBC Scores and Long-Term Outcomes in Patients With Primary Biliary Cholangitis

被引：87

作者：

Honda, Akira ^{[1
]}

Tanaka, Atsushi ^{[2
]}

Kaneko, Tetsuji ^{[3
]}

Komori, Atsumasa ^{[4
]}

Abe, Masanori ^{[5
]}

Inao, Mie ^{[6
]}

Namisaki, Tadashi ^{[7
]}

Hashimoto, Naoaki ^{[8
]}

Kawata, Kazuhito ^{[9
]}

Takahashi, Atsushi ^{[10
]}

Ninomiya, Masashi ^{[11
]}

Kang, Jong-Hon ^{[12
]}

Arakawa, Mie ^{[13
]}

Yamagiwa, Satoshi ^{[14
]}

Joshita, Satoru ^{[15
]}

Umemura, Takeji ^{[15
]}

Sato, Ken ^{[16
]}

Kaneko, Akira ^{[17
]}

Kikuchi, Kentaro ^{[18
]}

Itakura, Jun ^{[19
]}

Nomura, Takako ^{[20
]}

Kakisaka, Keisuke ^{[21
]}

Fujii, Hideki ^{[22
]}

Kawada, Norifumi ^{[22
]}

Takikawa, Yasuhiro ^{[21
]}

Masaki, Tsutomu ^{[20
]}

Ohira, Hiromasa ^{[10
]}

Mochida, Satoshi ^{[6
]}

Yoshiji, Hitoshi ^{[7
]}

Iimuro, Satoshi ^{[3
]}

Matsuzaki, Yasushi ^{[1
]}

Takikawa, Hajime ^{[2
]}

机构：

[1] Tokyo Med Univ, Ibaraki Med Ctr, Dept Internal Med, Div Gastroenterol & Hepatol, Ibaraki, Japan

[2] Teikyo Univ, Sch Med, Dept Med, Tokyo, Japan

[3] Teikyo Univ, Teikyo Acad Res Ctr, Tokyo, Japan

[4] Natl Hosp Org NHO Nagasaki Med Ctr, Clin Res Ctr, Nagasaki, Japan

[5] Ehime Univ, Grad Sch Med, Dept Gastroenterol & Metabol, Matsuyama, Ehime, Japan

[6] Saitama Med Univ, Fac Med, Dept Gastroenterol & Hepatol, Saitama, Japan

[7] Nara Med Univ, Dept Internal Med 3, Nara, Japan

[8] Tokyo Teishin Hosp, Dept Gastroenterol, Tokyo, Japan

[9] Hamamatsu Univ Sch Med, Hepatol Div, Dept Internal Med, Hamamatsu, Shizuoka, Japan

[10] Fukushima Med Univ, Dept Gastroenterol, Sch Med, Fukushima, Japan

[11] Tohoku Univ, Div Gastroenterol, Grad Sch Med, Sendai, Miyagi, Japan

[12] Teine Keijinkai Hosp, Ctr Gastroenterol, Sapporo, Hokkaido, Japan

[13] Oita Univ, Dept Gastroenterol, Fac Med, Yufu City, Japan

[14] Niigata Univ, Dept Gastroenterol & Hepatol, Grad Sch Med & Dent Sci, Niigata, Japan

[15] Shinshu Univ, Sch Med, Dept Med, Div Gastroenterol & Hepatol, Matsumoto, Nagano, Japan

[16] Gunma Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Maebashi, Gunma, Japan

[17] NTT West Osaka Hosp, Dept Gastroenterol, Osaka, Japan

[18] Teikyo Univ, Mizonokuchi Hosp, Dept Internal Med 4, Sagamiko, Kanagawa, Japan

[19] Musashino Red Cross Hosp, Dept Gastroenterol & Hepatol, Tokyo, Japan

[20] Kagawa Univ, Dept Gastroenterol & Neurol, Takamatsu, Kagawa, Japan

[21] Iwate Med Univ, Div Hepatol, Dept Internal Med, Morioka, Iwate, Japan

[22] Osaka City Univ, Grad Sch Med, Dept Hepatol, Osaka, Japan

来源：

HEPATOLOGY | 2019年 / 70卷 / 06期

关键词：

PLACEBO-CONTROLLED TRIAL; URSODEOXYCHOLIC ACID; COMBINATION THERAPY; BIOCHEMICAL RESPONSE; FENOFIBRATE TREATMENT; INCOMPLETE RESPONSE; OBETICHOLIC ACID; CHINESE PATIENTS; SCORING SYSTEM; CIRRHOSIS;

D O I：

10.1002/hep.30552

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

In Japan, bezafibrate (BF) is a second-line 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-PBC 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-Meier analysis were compared with the predicted outcomes calculated using GLOBE and UK-PBC 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 +/- 0.080, which improved significantly to 0.115 +/- 0.085 (P < 0.0001) after 1 year of combination therapy. The real liver transplant-free 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-related death compared with those predicted by UK-PBC risk score before introducing BF, but the predicted risk was significantly reduced by the addition of BF (P < 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-related death in patients who, after 1 year of UDCA monotherapy, had normal serum bilirubin (adjusted hazard ratio 0.09, 95% confidence interval 0.01-0.60, P = 0.013). Conclusion: Addition of BF to UDCA monotherapy improves not only GLOBE and UK-PBC scores but also the long-term prognosis of PBC patients, especially those with early-stage PBC.

引用

页码：2035 / 2046

页数：12

共 48 条

[1] The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments [J].

Austin, Peter C. .

STATISTICS IN MEDICINE, 2014, 33 (07) :1242-1258

[2] EASL Clinical Practice Guidelines: Management of cholestatic liver diseases [J].

Beuers, Ulrich ;

Boberg, Kirsten M. ;

Chapman, Roger W. ;

Chazouilleres, Olivier ;

Invernizzi, Pietro ;

Jones, David E. J. ;

Lammert, Frank ;

Pares, Albert ;

Trauner, Michael .

JOURNAL OF HEPATOLOGY, 2009, 51 (02) :237-267

[3] The UK-PBC Risk Scores: Derivation and Validation of a Scoring System for Long-Term Prediction of End-Stage Liver Disease in Primary Biliary Cholangitis [J].

Carbone, Marco ;

Sharp, Stephen J. ;

Flack, Steve ;

Paximadas, Dimitrios ;

Spiess, Kelly ;

Adgey, Carolyn ;

Griffiths, Laura ;

Lim, Reyna ;

Trembling, Paul ;

Williamson, Kate ;

Wareham, Nick J. ;

Aldersley, Mark ;

Bathgate, Andrew ;

Burroughs, Andrew K. ;

Heneghan, Michael A. ;

Neuberger, James M. ;

Thorburn, Douglas ;

Hirschfield, Gideon M. ;

Cordell, Heather J. ;

Alexander, Graeme J. ;

Jones, David E. J. ;

Sandford, Richard N. ;

Mells, George F. .

HEPATOLOGY, 2016, 63 (03) :930-950

[4] Combined ursodeoxycholic acid (UDCA) and fenofibrate in primary biliary cholangitis patients with incomplete UDCA response may improve outcomes [J].

Cheung, A. C. ;

Lapointe-Shaw, L. ;

Kowgier, M. ;

Meza-Cardona, J. ;

Hirschfield, G. M. ;

Janssen, H. L. A. ;

Feld, J. J. .

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2016, 43 (02) :283-293

[5] A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis [J].

Corpechot, C. ;

Chazouilleres, O. ;

Rousseau, A. ;

Le Gruyer, A. ;

Habersetzer, F. ;

Mathurin, P. ;

Goria, O. ;

Potier, P. ;

Minello, A. ;

Silvain, C. ;

Abergel, A. ;

Debette-Gratien, M. ;

Larrey, D. ;

Roux, O. ;

Bronowicki, J. -P. ;

Boursier, J. ;

de Ledinghen, V. ;

Heurgue-Berlot, A. ;

Nguyen-Khac, E. ;

Zoulim, F. ;

Ollivier-Hourmand, I. ;

Zarski, J. -P. ;

Nkontchou, G. ;

Lemoinne, S. ;

Humbert, L. ;

Rainteau, D. ;

Lefevre, G. ;

de Chaisemartin, L. ;

Chollet-Martin, S. ;

Gaouar, F. ;

Admane, F. -H. ;

Simon, T. ;

Poupon, R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (23) :2171-2181

[6] The effect of ursodeoxycholic acid therapy on the natural course of primary biliary cirrhosis [J].

Corpechot, C ;

Carrat, F ;

Bahr, A ;

Chrétien, Y ;

Poupon, RE ;

Poupon, R .

GASTROENTEROLOGY, 2005, 128 (02) :297-303

[7] Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis [J].

Corpechot, Christophe ;

Abenavoli, Ludovico ;

Rabahi, Nabila ;

Chretien, Yves ;

Andreani, Tony ;

Johanet, Catherine ;

Chazouilleres, Olivier ;

Poupon, Raoul .

HEPATOLOGY, 2008, 48 (03) :871-877

[8] Early primary biliary cirrhosis: Biochemical response to treatment and prediction of long-term outcome [J].

Corpechot, Christophe ;

Chazouilleres, Olivier ;

Poupon, Raoul .

JOURNAL OF HEPATOLOGY, 2011, 55 (06) :1361-1367

[9]

Dohmen K, 2004, WORLD J GASTROENTERO, V10, P894

[10] Fibrates as Adjuvant Therapy for Chronic Cholestatic Liver Disease: Its Time Has Come [J].

Ghonem, Nisanne S. ;

Boyer, James L. .

HEPATOLOGY, 2013, 57 (05) :1691-1693

← 1 2 3 4 5 →