NASH: A glance at the landscape of pharmacological treatment

被引:34
作者
Brodosi, Lucia [1 ]
Marchignoli, Francesca [1 ]
Petroni, Maria Letizia [1 ]
Marchesini, Giulio [1 ]
机构
[1] Alma Mater Univ, Unit Metab Dis & Clin Dietet, Bologna, Italy
关键词
Bile acids; Fatty liver; Gliflozins; GLP-1; agonists; PPARs; FATTY LIVER-DISEASE; NONALCOHOLIC STEATOHEPATITIS; HEPATIC STEATOSIS; CCR2/CCR5; ANTAGONIST; PEPTIDE-1; RECEPTOR; OBETICHOLIC ACID; BILE-ACIDS; FIBROSIS; FXR; AGONIST;
D O I
10.5604/16652681.1212318
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
The role of nonalcoholic fatty liver disease, namely nonalcoholic steatohepatitis (NASH), as risk factor for liver- and non-liver-related morbidity and mortality has been extensively reported. In addition to lifestyle changes, capable of removing the metabolic factors driving disease progression, there is an urgent need for drugs able to reduce hepatic necroinflammation without worsening of fibrosis. This goal is considered by regulatory agencies as surrogate marker to define the effectiveness in pharmacological compounds in NASH, and fast-track approval was granted by the Food and Drug Administration in consideration of disease severity and unmet medical needs. Several compounds are in the pipeline of pharmaceutical industries and are being studied in phase II trials, but only a few (obeticholic acid, elafibranor) have started phase III trials. This concise review is intended to offer a systematic analysis of the most promising therapeutic intervention in NASH. In conclusion, there is reasonable expectation that drug may help curb the burden of NASH, and we look forward to obtaining solid data on their long-term safety and effectiveness. However, we should not forget that behavioral interventions remain a mandatory background treatment, able to stop disease progression in compliant overweight/ obese patients, with results that compare favorably with - and add to - the beneficial effects of drug treatment.
引用
收藏
页码:673 / 681
页数:9
相关论文
共 69 条
[1]
Farnesoid X receptor targeting to treat nonalcoholic steatohepatitis [J].
Adorini, Luciano ;
Pruzanski, Mark ;
Shapiro, David .
DRUG DISCOVERY TODAY, 2012, 17 (17-18) :988-997
[2]
Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study [J].
Armstrong, Matthew James ;
Gaunt, Piers ;
Aithal, Guruprasad P. ;
Barton, Darren ;
Hull, Diana ;
Parker, Richard ;
Hazlehurst, Jonathan M. ;
Guo, Kathy ;
Abouda, George ;
Aldersley, Mark A. ;
Stocken, Deborah ;
Gough, Stephen C. ;
Tomlinson, Jeremy W. ;
Brown, Rachel M. ;
Huebscher, Stefan G. ;
Newsome, Philip N. .
LANCET, 2016, 387 (10019) :679-690
[3]
Biology of incretins: GLP-1 and GIP [J].
Baggio, Laurie L. ;
Drucker, Daniel J. .
GASTROENTEROLOGY, 2007, 132 (06) :2131-2157
[4]
Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial [J].
Bailey, Clifford J. ;
Gross, Jorge L. ;
Pieters, Anne ;
Bastien, Arnaud ;
List, James F. .
LANCET, 2010, 375 (9733) :2223-2233
[5]
Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment [J].
Barry-Hamilton, Vivian ;
Spangler, Rhyannon ;
Marshall, Derek ;
McCauley, Scott ;
Rodriguez, Hector M. ;
Oyasu, Miho ;
Mikels, Amanda ;
Vaysberg, Maria ;
Ghermazien, Haben ;
Wai, Carol ;
Garcia, Carlos A. ;
Velayo, Arleene C. ;
Jorgensen, Brett ;
Biermann, Donna ;
Tsai, Daniel ;
Green, Jennifer ;
Zaffryar-Eilot, Shelly ;
Holzer, Alison ;
Ogg, Scott ;
Thai, Dung ;
Neufeld, Gera ;
Van Vlasselaer, Peter ;
Smith, Victoria .
NATURE MEDICINE, 2010, 16 (09) :1009-U107
[6]
Glucagon-like peptide-1 reduces hepatic lipogenesis via activation of AMP-activated protein kinase [J].
Ben-Shlomo, Shani ;
Zvibel, Isabel ;
Shnell, Mati ;
Shlomai, Amir ;
Chepurko, Elena ;
Halpern, Zamir ;
Barzilai, Nir ;
Oren, Ran ;
Fishman, Sigal .
JOURNAL OF HEPATOLOGY, 2011, 54 (06) :1214-1223
[7]
Changing nomenclature for PBC: From 'cirrhosis' to 'cholangitis' [J].
Beuers, Ulrich ;
Gershwin, M. Eric ;
Gish, Robert G. ;
Invernizzi, Pietro ;
Jones, David E. J. ;
Lindor, Keith ;
Ma, Xiong ;
Mackay, Ian R. ;
Pares, Albert ;
Tanaka, Atsushi ;
Vierling, John M. ;
Poupon, Raoul .
CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY, 2015, 39 (05) :E57-E59
[8]
Peroxisome proliferator-activated receptor δ: a multifaceted metabolic player [J].
Bojic, Lazar A. ;
Huff, Murray W. .
CURRENT OPINION IN LIPIDOLOGY, 2013, 24 (02) :171-177
[9]
Dual Peroxisome Proliferator-Activated Receptor α/δ Agonist GFT505 Improves Hepatic and Peripheral Insulin Sensitivity in Abdominally Obese Subjects [J].
Cariou, Bertrand ;
Hanf, Remy ;
Lambert-Porcheron, Stephanie ;
Zair, Yassine ;
Sauvinet, Valerie ;
Noel, Benoit ;
Flet, Laurent ;
Vidal, Hubert ;
Staels, Bart ;
Laville, Martine .
DIABETES CARE, 2013, 36 (10) :2923-2930
[10]
GFT505 for the treatment of nonalcoholic steatohepatitis and type 2 diabetes [J].
Cariou, Bertrand ;
Staels, Bart .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2014, 23 (10) :1441-1448