New and emerging treatments for metabolic dysfunction-associated steatohepatitis

被引:42
作者
Tincopa, Monica A. [1 ]
Anstee, Quentin M. [2 ,3 ]
Loomba, Rohit [1 ,4 ]
机构
[1] Univ Calif San Diego, MASLD Res Ctr, Div Gastroenterol & Hepatol, La Jolla, CA 92103 USA
[2] Newcastle Univ, Translat & Clin Res Inst, Fac Med Sci, Newcastle Upon Tyne, England
[3] Newcastle Upon Tyne Hosp NHS Trust, Newcastle NIHR Biomed Res Ctr, Newcastle Upon Tyne, England
[4] Univ Calif San Diego, Sch Publ Hlth, La Jolla, CA 92103 USA
关键词
NONALCOHOLIC FATTY LIVER; MAGNETIC-RESONANCE ELASTOGRAPHY; OBETICHOLIC ACID; PROSPECTIVE DERIVATION; NONINVASIVE DIAGNOSIS; SCORING SYSTEM; CANCER RISK; VITAMIN-E; FIBROSIS; DISEASE;
D O I
10.1016/j.cmet.2024.03.011
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Metabolic dysfunction-associated steatohepatitis (MASH) is a leading etiology of chronic liver disease worldwide, with increasing incidence and prevalence in the setting of the obesity epidemic. MASH is also a leading indication for liver transplantation, given its associated risk of progression to end-stage liver disease. A key challenge in managing MASH is the lack of approved pharmacotherapy. In its absence, lifestyle interventions with a focus on healthy nutrition and regular physical activity have been the cornerstone of therapy. Realworld efficacy and sustainability of lifestyle interventions are low, however. Pharmacotherapy development for MASH is emerging with promising data from several agents with different mechanisms of action (MOAs) in phase 3 clinical trials. In this review, we highlight ongoing challenges and potential solutions in drug development for MASH and provide an overview of available data from emerging therapies across multiple MOAs.
引用
收藏
页码:912 / 926
页数:15
相关论文
共 106 条
[1]   Recent advances in the development of farnesoid X receptor agonists [J].
Ali, Ahmad H. ;
Carey, Elizabeth J. ;
Lindor, Keith D. .
ANNALS OF TRANSLATIONAL MEDICINE, 2015, 3 (01)
[2]  
Alkhouri N, 2022, HEPATOLOGY, V76, pS803
[3]   Safety and efficacy of combination therapy with semaglutide, cilofexor and firsocostat in patients with non-alcoholic steatohepatitis: A randomised, open-label phase II trial [J].
Alkhouri, Naim ;
Herring, Robert ;
Kabler, Heidi ;
Kayali, Zeid ;
Hassanein, Tarek ;
Kohli, Anita ;
Huss, Ryan S. ;
Zhu, Yanni ;
Billin, Andrew N. ;
Damgaard, Lars Holm ;
Buchholtz, Kristine ;
Kjaer, Mette Skalshoi ;
Balendran, Clare ;
Myers, Robert P. ;
Loomba, Rohit ;
Noureddin, Mazen .
JOURNAL OF HEPATOLOGY, 2022, 77 (03) :607-618
[4]   Clinical Utility of Magnetic Resonance Imaging Biomarkers for Identifying Nonalcoholic Steatohepatitis Patients at High Risk of Progression: A Multicenter Pooled Data and Meta-Analysis [J].
Andersson, Anneli ;
Kelly, Matt ;
Imajo, Kento ;
Nakajima, Atsushi ;
Fallowfield, Jonathan A. ;
Hirschfield, Gideon ;
Pavlides, Michael ;
Sanyal, Arun J. ;
Noureddin, Mazen ;
Banerjee, Rajarshi ;
Dennis, Andrea ;
Harrison, Stephen .
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2022, 20 (11) :2451-+
[5]  
[Anonymous], 2016, OB OV
[6]   Tropifexor plus cenicriviroc combination versus monotherapy in nonalcoholic steatohepatitis: Results from the phase 2b TANDEM study [J].
Anstee, Quentin M. ;
Lucas, Kathryn J. ;
Francque, Sven ;
Abdelmalek, Manal F. ;
Sanyal, Arun J. ;
Ratziu, Vlad ;
Gadano, Adrian C. ;
Rinella, Mary ;
Charlton, Michael ;
Loomba, Rohit ;
Mena, Edward ;
Schattenberg, Joern M. ;
Noureddin, Mazen ;
Lazas, Donald ;
Goh, George B. B. ;
Sarin, Shiv K. ;
Yilmaz, Yusuf ;
Martic, Miljen ;
Stringer, Rowan ;
Kochuparampil, Jossy ;
Chen, Li ;
Rodriguez-Araujo, Gerardo ;
Chng, Elaine ;
Naoumov, Nikolai V. ;
Brass, Clifford ;
Pedrosa, Marcos C. .
HEPATOLOGY, 2023, 78 (04) :1223-1239
[7]   Research in Brief [J].
Baker, Holly .
LANCET GASTROENTEROLOGY & HEPATOLOGY, 2023, 8 (06) :508-508
[8]   From NASH to HCC: current concepts and future challenges [J].
Anstee, Quentin M. ;
Reeves, Helen L. ;
Kotsiliti, Elena ;
Govaere, Olivier ;
Heikenwalder, Mathias .
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2019, 16 (07) :411-428
[9]   Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients [J].
Bedossa, Pierre ;
Poitou, Christine ;
Veyrie, Nicolas ;
Bouillot, Jean-Luc ;
Basdevant, Arnaud ;
Paradis, Valerie ;
Tordjman, Joan ;
Clement, Karine .
HEPATOLOGY, 2012, 56 (05) :1751-1759
[10]   Complexity of ballooned hepatocyte feature recognition: Defining a training atlas for artificial intelligence-based imaging in NAFLD [J].
Brunt, Elizabeth M. ;
Clouston, Andrew D. ;
Goodman, Zachary ;
Guy, Cynthia ;
Kleiner, David E. ;
Lackner, Carolin ;
Tiniakos, Dina G. ;
Wee, Aileen ;
Yeh, Matthew ;
Leow, Wei Qiang ;
Chng, Elaine ;
Ren, Yayun ;
Bee, George Goh Boon ;
Powell, Elizabeth E. ;
Rinella, Mary ;
Sanyal, Arun J. ;
Neuschwander-Tetri, Brent ;
Younossi, Zobair ;
Charlton, Michael ;
Ratziu, Vlad ;
Harrison, Stephen A. ;
Tai, Dean ;
Anstee, Quentin M. .
JOURNAL OF HEPATOLOGY, 2022, 76 (05) :1030-1041