Current and experimental pharmacotherapy for the management of non-alcoholic fatty liver disease

被引:3
作者
Katsarou, Angeliki [1 ,4 ]
Tsioulos, Georgios [2 ]
Kassi, Eva [3 ]
Chatzigeorgiou, Antonios [4 ]
机构
[1] 251 Hellen Airforce Gen Hosp, 1 PKanellopoulou Str, Athens 11525, Greece
[2] Natl & Kapodistrian Univ Athens, Univ Gen Hosp Attikon, Dept Internal Med 4, Med Sch, 1 Rimini Str, Athens 12462, Greece
[3] Natl & Kapodistrian Univ Athens, Med Sch, Dept Biol Chem, Athens 11527, Greece
[4] Natl & Kapodistrian Univ Athens, Med Sch, Dept Physiol, 75 Mikras Asias Str, Athens 11527, Greece
来源
HORMONES-INTERNATIONAL JOURNAL OF ENDOCRINOLOGY AND METABOLISM | 2024年 / 23卷 / 04期
关键词
NAFLD; MASLD; Treatment; Drugs; Fibrosis; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; OBETICHOLIC ACID; STEATOHEPATITIS; GALECTIN-3; ORLISTAT; OBESITY; NASH; PIOGLITAZONE; LIRAGLUTIDE;
D O I
10.1007/s42000-024-00588-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, with its incidence increasing in parallel with the global prevalence of obesity and type 2 diabetes mellitus. Despite our steadily increasing knowledge of its pathogenesis, there is as yet no available pharmacotherapy specifically tailored for NAFLD. To define the appropriate management, it is important to clarify the context in which the disease appears. In the case of concurrent metabolic comorbidities, NAFLD patients are treated by targeting these comorbidities, such as diabetes and obesity. Thus, GLP-1 analogs, PPAR, and SGLT2 inhibitors have recently become central to the treatment of NAFLD. In parallel, randomized trials are being conducted to explore new agents targeting known pathways involved in NAFLD progression. However, there is an imperative need to intensify the effort to design new, safe drugs with biopsy-proven efficacy. Of note, the main target of the pharmacotherapy should be directed to the regression of fibrotic NASH, as this histologic stage has been correlated with increased overall as well as liver-related morbidity and mortality. Herein we discuss the drugs currently at the forefront of NAFLD treatment.
引用
收藏
页码:621 / 636
页数:16
相关论文
共 124 条
[31]   Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes [J].
Frias, Juan P. ;
Davies, Melanie J. ;
Rosenstock, Julio ;
Manghi, Federico C. Perez ;
Lando, Laura Fernandez ;
Bergman, Brandon K. ;
Liu, Bing ;
Cui, Xuewei ;
Brown, Katelyn .
NEW ENGLAND JOURNAL OF MEDICINE, 2021, 385 (06) :503-515
[32]   Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial [J].
Gastaldelli, Amalia ;
Cusi, Kenneth ;
Fernandez Lando, Laura ;
Bray, Ross ;
Brouwers, Bram ;
Rodriguez, Angel .
LANCET DIABETES & ENDOCRINOLOGY, 2022, 10 (06) :393-406
[33]   From NASH to diabetes and from diabetes to NASH: Mechanisms and treatment options [J].
Gastaldelli, Amalia ;
Cusi, Kenneth .
JHEP REPORTS, 2019, 1 (04) :312-328
[34]   Saroglitazar, a PPAR-α/γ Agonist, for Treatment of NAFLD: A Randomized Controlled Double-Blind Phase 2 Trial [J].
Gawrieh, Samer ;
Noureddin, Mazen ;
Loo, Nicole ;
Mohseni, Rizwana ;
Awasty, Vivek ;
Cusi, Kenneth ;
Kowdley, Kris V. ;
Lai, Michelle ;
Schiff, Eugene ;
Parmar, Deven ;
Patel, Pankaj ;
Chalasani, Naga .
HEPATOLOGY, 2021, 74 (04) :1809-1824
[35]   Effects of liraglutide on weight, satiation, and gastric functions in obesity: a randomised, placebo-controlled pilot trial [J].
Halawi, Houssam ;
Khemani, Disha ;
Eckert, Deborah ;
O'Neill, Jessica ;
Kadouh, Hoda ;
Grothe, Karen ;
Clark, Matthew M. ;
Burton, Duane D. ;
Vella, Adrian ;
Acosta, Andres ;
Zinsmeister, Alan R. ;
Camilleri, Michael .
LANCET GASTROENTEROLOGY & HEPATOLOGY, 2017, 2 (12) :890-899
[36]   Randomised clinical study: GR-MD-02, a galectin-3 inhibitor, vs. placebo in patients having non-alcoholic steatohepatitis with advanced fibrosis [J].
Harrison, S. A. ;
Marri, S. R. ;
Chalasani, N. ;
Kohli, R. ;
Aronstein, W. ;
Thompson, G. A. ;
Irish, W. ;
Miles, M. V. ;
Xanthakos, S. A. ;
Lawitz, E. ;
Noureddin, M. ;
Schiano, T. D. ;
Siddiqui, M. ;
Sanyal, A. ;
Neuschwander-Tetri, B. A. ;
Traber, P. G. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2016, 44 (11-12) :1183-1198
[37]   A pilot study of orlistat treatment in obese, non-alcoholic steatohepatitis patients [J].
Harrison, SA ;
Fincke, C ;
Helinski, D ;
Torgerson, S ;
Hayashi, P .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2004, 20 (06) :623-628
[38]   A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis [J].
Harrison, Stephen A. ;
Bedossa, Pierre ;
Guy, Cynthia D. ;
Schattenberg, Joern M. ;
Loomba, Rohit ;
Taub, Rebecca ;
Labriola, Dominic ;
Moussa, Sam E. ;
Neff, Guy W. ;
Rinella, Mary E. ;
Anstee, Quentin M. ;
Abdelmalek, Manal F. ;
Younossi, Zobair ;
Baum, Seth J. ;
Francque, Sven ;
Charlton, Michael R. ;
Newsome, Philip N. ;
Lanthier, Nicolas ;
Schiefke, Ingolf ;
Mangia, Alessandra ;
Pericas, Juan M. ;
Patil, Rashmee ;
Sanyal, Arun J. ;
Noureddin, Mazen ;
Bansal, Meena B. ;
Alkhouri, Naim ;
Castera, Laurent ;
Rudraraju, Madhavi ;
Ratziu, Vlad .
NEW ENGLAND JOURNAL OF MEDICINE, 2024, 390 (06) :497-509
[39]   A randomized, double-blind, placebo-controlled phase IIa trial of efruxifermin for patients with compensated NASH cirrhosis [J].
Harrison, Stephen A. ;
Ruane, Peter J. ;
Freilich, Bradley ;
Neff, Guy ;
Patil, Rashmee ;
Behling, Cynthia ;
Hu, Chen ;
Shringarpure, Reshma ;
de Temple, Brittany ;
Fong, Erica ;
Tillman, Erik J. ;
Rolph, Timothy ;
Cheng, Andrew ;
Yale, Kitty .
JHEP REPORTS, 2023, 5 (01)
[40]   Rencofilstat, a cyclophilin inhibitor: A phase 2a, multicenter, single-blind, placebo-controlled study in F2/F3 NASH [J].
Harrison, Stephen A. ;
Mayo, Patrick R. ;
Hobbs, Todd M. ;
Canizares, Carlos ;
Foster, Erin P. ;
Zhao, Caroline ;
Ure, Daren R. ;
Trepanier, Daniel J. ;
Greytok, Jill A. ;
Foster, Robert T. .
HEPATOLOGY COMMUNICATIONS, 2022, 6 (12) :3379-3392