Ezetimibe for the treatment of non-alcoholic fatty liver disease: A meta-analysis

被引:64
作者
Nakade, Yukiomi [1 ]
Murotani, Kenta [2 ]
Inoue, Tadahisa [1 ]
Kobayashi, Yuji [1 ]
Yamamoto, Takaya [1 ]
Ishii, Norimitsu [1 ]
Ohashi, Tomohiko [1 ]
Ito, Kiyoaki [1 ]
Fukuzawa, Yoshitaka [1 ]
Yoneda, Masashi [1 ]
机构
[1] Aichi Med Univ, Div Gastroenterol & Hepatol, Dept Internal Med, 1-1 Karimata Yazako Nagakute, Nagakute, Aichi 4801195, Japan
[2] Aichi Med Univ, Div Biostat, Clin Res Ctr, Nagakute, Aichi, Japan
关键词
ezetimibe; fibrosis; inflammation; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; INSULIN-RESISTANCE; DIETARY-CHOLESTEROL; STEATOHEPATITIS; EFFICACY; STEATOSIS; THERAPY; GLUCOSE; PLACEBO; RATHER;
D O I
10.1111/hepr.12887
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
AimSeveral studies on the efficacy of ezetimibe, a potent inhibitor of cholesterol absorption, in treating non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have been published; however, the results are inconsistent. We undertook a meta-analysis to evaluate the efficacy of ezetimibe in treating NAFLD and NASH. MethodsPubMed, Medline, and Cochrane Library Full Text Database were searched until June 2016. The main inclusion criteria included original studies investigating the use of ezetimibe for the treatment of NAFLD and NASH. Identification of published work and data extraction were carried out by two reviewers based on the inclusion and exclusion criteria. All analyses were carried out using Comprehensive Meta-Analysis version 3 software. ResultsAn initial search identified 103 peer-reviewed articles and abstracts. Six studies (two randomized controlled and four single-arm trials) involving 273 participants with NAFLD and NASH were identified. Ezetimibe significantly reduced serum aspartate aminotransferase, alanine aminotransferase, and -glutamyl transpeptidase levels, and hepatic steatosis and hepatocyte ballooning. However, hepatic inflammation and fibrosis did not improve by ezetimibe treatment in patients with NAFLD and NASH. In randomized controlled trials, only hepatocyte ballooning improved with ezetimibe treatment. ConclusionsAlthough ezetimibe attenuated serum liver enzymes and hepatic steatosis and ballooning in six studies, it improved only hepatocyte ballooning in randomized controlled trials. Larger studies and more randomized placebo-controlled trials are necessary to determine the effects of ezetimibe on NAFLD and NASH.
引用
收藏
页码:1417 / 1428
页数:12
相关论文
共 35 条
[11]   Atorvastatin and Antioxidants for the Treatment of Nonalcoholic Fatty Liver Disease: The St Francis Heart Study Randomized Clinical Trial [J].
Foster, Temitope ;
Budoff, Matthew J. ;
Saab, Sammy ;
Ahmadi, Naser ;
Gordon, Craig ;
Guerci, Alan D. .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2011, 106 (01) :71-77
[12]   Hepatocyte free cholesterol lipotoxicity results from JNK1-mediated mitochondrial injury and is HMGB1 and TLR4-dependent [J].
Gan, Lay T. ;
Van Rooyen, Derrick M. ;
Koina, Mark E. ;
McCuskey, Robert S. ;
Teoh, Narcissus C. ;
Farrell, Geoffrey C. .
JOURNAL OF HEPATOLOGY, 2014, 61 (06) :1376-1384
[13]   The target of ezetimibe is Niemann-Pick Cl-Like 1 (NPC1L1) [J].
Garcia-Calvo, M ;
Lisnock, JM ;
Bull, HG ;
Hawes, BE ;
Burnett, DA ;
Braun, MP ;
Crona, JH ;
Davis, HR ;
Dean, DC ;
Detmers, PA ;
Graziano, MP ;
Hughes, M ;
MacIntyre, DE ;
Ogawa, A ;
O'Neill, KA ;
Iyer, SPN ;
Shevell, DE ;
Smith, MM ;
Tang, YS ;
Makarewicz, AM ;
Ujjainwalla, F ;
Altmann, SW ;
Chapman, KT ;
Thornberry, NA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (23) :8132-8137
[14]   Plasma transforming growth factor-β1 level and efficacy of α-tocopherol in patients with non-alcoholic steatohepatitis:: a pilot study [J].
Hasegawa, T ;
Yoneda, M ;
Nakamura, K ;
Makino, I ;
Terano, A .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2001, 15 (10) :1667-1672
[15]   Measuring inconsistency in meta-analyses [J].
Higgins, JPT ;
Thompson, SG ;
Deeks, JJ ;
Altman, DG .
BMJ-BRITISH MEDICAL JOURNAL, 2003, 327 (7414) :557-560
[16]   The Epidemiology of Nonalcoholic Fatty Liver Disease: A Global Perspective [J].
Lazo, Mariana ;
Clark, Jeanne M. .
SEMINARS IN LIVER DISEASE, 2008, 28 (04) :339-350
[17]   Ezetimibe for the Treatment of Nonalcoholic Steatohepatitis: Assessment by Novel Magnetic Resonance Imaging and Magnetic Resonance Elastography in a Randomized Trial (MOZART Trial) [J].
Loomba, Rohit ;
Sirlin, Claude B. ;
Ang, Brandon ;
Bettencourt, Ricki ;
Jain, Rashmi ;
Salotti, Joanie ;
Soaft, Linda ;
Hooker, Jonathan ;
Kono, Yuko ;
Bhatt, Archana ;
Hernandez, Laura ;
Phirum Nguyen ;
Noureddin, Mazen ;
Haufe, William ;
Hooker, Catherine ;
Yin, Meng ;
Ehman, Richard ;
Lin, Grace Y. ;
Valasek, Mark A. ;
Brenner, David A. ;
Richards, Lisa .
HEPATOLOGY, 2015, 61 (04) :1239-1250
[18]   Mitochondrial free cholesterol loading sensitizes to TNF- and Fas-mediated steatohepatitis [J].
Mari, Montserrat ;
Caballero, Francisco ;
Colell, Anna ;
Morales, Albert ;
Caballeria, Juan ;
Fernandez, Anna ;
Enrich, Carlos ;
Fernandez-Checa, Jose C. ;
Garcia-Ruiz, Carmen .
CELL METABOLISM, 2006, 4 (03) :185-198
[19]   Lipid-induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet [J].
Matsuzawa, Naoto ;
Takamura, Toshinari ;
Kurita, Seiichiro ;
Misu, Hirofumi ;
Ando, Hitoshi ;
Yokoyama, Masayoshi ;
Honda, Masao ;
Zen, Yoh ;
Nakanuma, Yasuni ;
Miyamoto, Ken-Ichi ;
Kaneko, Shuichi .
HEPATOLOGY, 2007, 46 (05) :1392-1403
[20]   Nonalcoholic fatty liver disease: A spectrum of clinical and pathological severity [J].
Matteoni, CA ;
Younossi, ZM ;
Gramlich, T ;
Boparai, N ;
Liu, YC ;
McCullough, AJ .
GASTROENTEROLOGY, 1999, 116 (06) :1413-1419