Treatment of primary biliary cholangitis ursodeoxycholic acid non-responders: A systematic review

被引：28
作者：
Suraweera, Duminda [1 ]
Rahal, Harman [2 ]
Jimenez, Melissa [3 ]
Viramontes, Matthew [3 ]
Choi, Gina [3 ]
Saab, Sammy [2 ,3 ]
机构：
[1] Olive View Med Ctr, Dept Med, Sylmar, CA USA
[2] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA
[3] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA
来源：
LIVER INTERNATIONAL | 2017年 / 37卷 / 12期
关键词：
fenofibrate; non-responder; pharmacology; primary biliary cholangitis; ursodeoxycholic acid; BIOCHEMICAL RESPONSE; CONTROLLED-TRIAL; MYCOPHENOLATE-MOFETIL; FENOFIBRATE TREATMENT; COMBINATION THERAPY; INCOMPLETE RESPONSE; SUBOPTIMAL RESPONSE; OBETICHOLIC ACID; ORAL BUDESONIDE; END-POINTS;
D O I：
10.1111/liv.13477
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
Background: Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is a chronic cholestatic liver disease characterized by an immune mediated destruction of intrahepatic bile ducts. Ursodeoxycholic acid (UDCA) has been the primary medication for the treatment of PBC, resulting in improved liver tests, resolution of symptoms and increased transplant free survival. However, not all patients respond to UDCA. The aim of this systematic review is to provide an evidence based assessment of the medications that have been studied in patients who are refractory to UDCA. Methods: We performed a systematic literature search on MEDLINE and the Cochrane Database of Systematic Reviews of the published literature. A total of 23 articles fulfilling our inclusion criteria were found. Results: Several studies have shown an improvement in liver biochemistries with the use of obeticholic acid in conjunction with UDCA. Fibrates, including fenofibrate and bezafibrate, have evidence supporting benefit in this population but need more robust studies to confirm these observational results. Neither obeticholic acid nor fibrates have shown to increase transplant free survival. While there may be some benefit with methotrexate, colchicine, budesonide, mycophenolate mofetil and azathioprine, these findings were not consistent and the benefits were marginal. Further investigation is needed. Conclusion: In patients with PBC refractory to UDCA, obeticholic acid or a fibrate is a reasonable choice as an adjunctive treatment to UDCA. Further investigation with randomized controlled trials is needed to provide high quality evidence to formulate standardized therapies in this difficult to treat population.
引用
收藏
页码：1877 / 1886
页数：10
相关论文
共 53 条
[1]   Methotrexate induced mitochondrial injury and cytochrome c release in rat liver hepatocytes [J].
Al Maruf, Abdullah ;
O'Brien, Peter J. ;
Naserzadeh, Parvaneh ;
Fathian, Rozhina ;
Salimi, Ahmad ;
Pourahmad, Jalal .
DRUG AND CHEMICAL TOXICOLOGY, 2018, 41 (01) :51-61
[2]   Oral budesonide in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid [J].
Angulo, P ;
Jorgensen, RA ;
Keach, JC ;
Dickson, ER ;
Smith, C ;
Lindor, KD .
HEPATOLOGY, 2000, 31 (02) :318-323
[3]   Utilization of the Mayo risk score in patients with primary biliary cirrhosis receiving ursodeoxycholic acid [J].
Angulo, P ;
Lindor, KD ;
Therneau, TM ;
Jorgensen, RA ;
Malinchoc, M ;
Kamath, PS ;
Dickson, ER .
LIVER, 1999, 19 (02) :115-121
[4]   Silymarin in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid [J].
Angulo, P ;
Patel, T ;
Jorgensen, RA ;
Therneau, TM ;
Lindor, KD .
HEPATOLOGY, 2000, 32 (05) :897-900
[5]  
[Anonymous], 2000, Cochrane Database Syst Rev, DOI DOI 10.1002/14651858.CD000067
[6]   Biochemical response to ursodeoxycholic acid predicts long-term outcome in Japanese patients with primary biliary cirrhosis [J].
Azemoto, Nobuaki ;
Kumagi, Teru ;
Abe, Masanori ;
Konishi, Ichiro ;
Matsuura, Bunzo ;
Hiasa, Yoichi ;
Onji, Morikazu .
HEPATOLOGY RESEARCH, 2011, 41 (04) :310-317
[7]   Methotrexate therapy for the symptomatic treatment of primary biliary cirrhosis patients, who are biochemical incomplete responders to ursodeoxycholic acid therapy [J].
Babatin, M. A. ;
Sanai, F. M. ;
Swain, M. G. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2006, 24 (05) :813-820
[8]   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
[9]   Methotrexate improves biochemical tests in patients with primary biliary cirrhosis who respond incompletely to ursodiol [J].
Bonis, PAL ;
Kaplan, M .
GASTROENTEROLOGY, 1999, 117 (02) :395-399
[10]   Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: A systematic review [J].
Boonstra, Kirsten ;
Beuers, Ulrich ;
Ponsioen, Cyriel Y. .
JOURNAL OF HEPATOLOGY, 2012, 56 (05) :1181-1188
123456