Efficacy and safety of fenofibrate add-on therapy in patients with primary biliary cholangitis refractory to ursodeoxycholic acid: A retrospective study and updated meta-analysis

被引：7

作者：

Xuan, Guoyun ^{[1
]}

Ding, Dawei ^{[1
]}

Ning, Liu ^{[2
]}

Hu, Yinan ^{[1
]}

Yang, Fangfang ^{[1
]}

Tian, Siyuan ^{[1
]}

Hao, Sun ^{[1
]}

Yang, Jiaqi ^{[1
]}

Ang, Xu ^{[1
]}

Guo, Guanya ^{[1
]}

Xi, Chen ^{[2
]}

Shang, Yulong ^{[1
]}

Ying, Han ^{[1
]}

机构：

[1] Air Forcce Med Univ, Mil Med Univ 4, Xijing Hosp Digest Dis, Natl Clin Res Ctr Digest Dis,State Key Lab Canc Bi, Xian, Peoples R China

[2] Air Force Hosp Southern Theater PLA, Med Serv, Guangzhou, Peoples R China

来源：

FRONTIERS IN PHARMACOLOGY | 2022年 / 13卷

基金：

中国国家自然科学基金;

关键词：

primary biliary cholangitis; monotherapy; meta-analysis; clinical trial; fenofibrate; ACTIVATED RECEPTOR-ALPHA; LONG-TERM PROGNOSIS; BIOCHEMICAL RESPONSE; CIRRHOSIS; EXPRESSION; UDCA;

D O I：

10.3389/fphar.2022.948362

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Background: Ursodeoxycholic acid (UDCA) is currently used for the treatment of primary biliary cholangitis (PBC), but some people do not respond well to UDCA. It reported that the combination of fenofibrate and UDCA can improve the clinical indices in these patients. However, more high-quality evidence is needed to improve guideline recommendations. Methods: Through an updated meta-analysis, studies included were valued by the Cochrane Evaluation Manual and Robins-I. Biochemical and clinical indicator changes in UDCA-refractory PBC patients receiving combination therapy were analyzed by Revman 5.42. Then, we explored the influence of fenofibrate dose and the effectiveness and safety of long-term application by retrospective cohort study. Results: Our meta-analysis included nine publications with a total of 389 patients, including 216 treated with UDCA alone and 173 who received combination therapy. The meta-analysis showed that combination therapy was more effective than UDCA monotherapy in decreasing biochemical parameters, such as ALP, GGT, IgM, and TG. However, the occurrence of pruritus and adverse events was slightly higher with combination therapy than with UDCA monotherapy. A total of 156 patients were included in our cohort study: 68 patients underwent UDCA monotherapy, and 88 patients underwent combination therapy. Among UDCA-refractory patients, fenofibrate add-on therapy significantly improved the ALP normalization rate. Conclusion: The combination of fenofibrate and UDCA can decrease biochemical parameters, of UDCA-refractory PBC patient. Furthermore, the efficacy and safety of long-term combination therapy were also confirmed in our cohort study.

引用

页数：12

共 37 条

[1]

Arroyo V, 1996, HEPATOLOGY, V23, P164, DOI 10.1002/hep.510230122

[2] Fibrates for the Treatment of Primary Biliary Cholangitis Unresponsive to Ursodeoxycholic Acid: An Exploratory Study [J].

Cancado, Guilherme Grossi Lopes ;

Couto, Claudia Alves ;

Guedes, Laura Vilar ;

Braga, Michelle Harriz ;

Terrabuio, Debora Raquel Benedita ;

Cancado, Eduardo Luiz Rachid ;

Ferraz, Maria Lucia Gomes ;

Villela-Nogueira, Cristiane Alves ;

Nardelli, Mateus Jorge ;

Faria, Luciana Costa ;

Oliveira, Elze Maria Gomes de ;

Rotman, Vivian ;

Mazo, Daniel Ferraz de Campos ;

Borges, Valeria Ferreira de Almeida e ;

Mendes, Liliana Sampaio Costa ;

Codes, Liana ;

Pessoa, Mario Guimaraes ;

Signorelli, Izabelle Venturini ;

Levy, Cynthia ;

Bittencourt, Paulo Lisboa .

FRONTIERS IN PHARMACOLOGY, 2022, 12

[3] 15-Deoxy-γ12,14-prostaglandin J2 Reduces Liver Impairment in a Model of ConA-Induced Acute Hepatic Inflammation by Activation of PPARγ and Reduction in NF-κB Activity (vol 2014, 215631, 2014) [J].

Chen, Kan ;

Li, Jingjing ;

Wang, Junshan ;

Xia, Yujing ;

Dai, Weiqi ;

Wang, Fan ;

Shen, Miao ;

Cheng, Ping ;

Zhang, Yan ;

Wang, Chengfen ;

Yang, Jing ;

Zhu, Rong ;

Zhang, Huawei ;

Zheng, Yuanyuan ;

Lu, Jie ;

Fan, Zhuoyi ;

Zhou, Yingqun ;

Guo, Chuanyong .

PPAR RESEARCH, 2014, 2014

[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]

Chinese Society of Hepatology Chinese Medical Association, 2022, Zhonghua Gan Zang Bing Za Zhi, V30, P264, DOI 10.3760/cma.j.cn112138-20211112-00794-1

[6] 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

[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] Hexa Histidine-Tagged Recombinant Human Cytoglobin Deactivates Hepatic Stellate Cells and Inhibits Liver Fibrosis by Scavenging Reactive Oxygen Species [J].

Dat, Ninh Quoc ;

Thuy, Le Thi Thanh ;

Hieu, Vu Ngoc ;

Hai, Hoang ;

Hoang, Dinh Viet ;

Thi Thanh Hai, Nguyen ;

Thuy, Tuong Thi Van ;

Komiya, Tohru ;

Rombouts, Krista ;

Dong, Minh Phuong ;

Hanh, Ngo Vinh ;

Hoang, Truong Huu ;

Sato-Matsubara, Misako ;

Daikoku, Atsuko ;

Kadono, Chiho ;

Oikawa, Daisuke ;

Yoshizato, Katsutoshi ;

Tokunaga, Fuminori ;

Pinzani, Massimo ;

Kawada, Norifumi .

HEPATOLOGY, 2021, 73 (06) :2527-2545

[10]

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

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