Promising therapies for treatment of nonalcoholic steatohepatitis

被引:29
作者
Noureddin, Mazen [1 ,2 ]
Zhang, Alice [2 ]
Loomb, Rohit [3 ,4 ]
机构
[1] Cedars Sinai Med Ctr, Comprehens Transplant Ctr, Div Digest & Liver Dis, Fatty Liver Program, Los Angeles, CA 90048 USA
[2] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA
[3] Univ Calif San Diego, Div Gastroenterol, La Jolla, CA USA
[4] Univ Calif San Diego, Div Epidemiol, La Jolla, CA USA
关键词
Non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; treatment for non-alcoholic fatty liver disease; treatment for non-alcoholic steatohepatitis; FATTY LIVER-DISEASE; GROWTH-FACTOR; 21; ACTIVATED RECEPTOR-ALPHA; CORONARY-HEART-DISEASE; TOLL-LIKE RECEPTORS; VITAMIN-D; HEPATIC STEATOSIS; INSULIN-RESISTANCE; ANGIOTENSIN-II; S-ADENOSYLMETHIONINE;
D O I
10.1080/14728214.2016.1220533
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: Non-alcoholic fatty liver disease (NAFLD) has become the most common etiology for abnormal aminotransferase levels and chronic liver disease. Its growing prevalence is largely linked to the presence of metabolic syndrome, particularly diabetes and insulin resistance. It is estimated that 60-80% of the type 2 diabetic population has NAFLD. NAFLD encompasses a range of conditions ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). A subset of patients with hepatic steatosis progress to NASH, while 15-20% of patients with NASH develop cirrhosis. This progression is thought to be multifactorial, and there are currently no FDA-approved medications for the treatment of NASH. Areas covered: We review drugs currently in Phase II and III clinical trials for treatment of NAFLD and NASH, including their mechanisms of action, relationship to the pathophysiology of NASH, and rationale for their development. Expert opinion: The treatment of NASH is complex and necessitates targeting a number of different pathways. Combination therapy, preferably tailored toward the disease stage and severity, will be needed to achieve maximum therapeutic effect. With multiple agents currently being developed, there may soon be an ability to effectively slow or even reverse the disease process in many NAFLD/NASH patients.
引用
收藏
页码:343 / 357
页数:15
相关论文
共 146 条
[1]   The natural history of nonalcoholic fatty liver disease: A population-based cohort study [J].
Adams, LA ;
Lymp, JF ;
St Sauver, J ;
Sanderson, SO ;
Lindor, KD ;
Feldstein, A ;
Angulo, P .
GASTROENTEROLOGY, 2005, 129 (01) :113-121
[2]   Antifibrotic agents for liver disease [J].
Albanis, E ;
Friedman, SL .
AMERICAN JOURNAL OF TRANSPLANTATION, 2006, 6 (01) :12-19
[3]   CHANGES IN TISSUE LIPIDS AND TISSUE HISTOLOGY RESULTING FROM ESSENTIAL FATTY ACID DEFICIENCY IN RATS [J].
ALFINSLATER, RB ;
BERNICK, S .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 1958, 6 (06) :613-624
[4]  
Aller R, 2011, EUR REV MED PHARMACO, V15, P1090
[5]   Omega-3 fatty acids improve hepatic steatosis in a murine model:: Potential implications for the marginal steatotic liver donor [J].
Alwayn, IPJ ;
Andersson, C ;
Zauscher, B ;
Gura, K ;
Nosé, V ;
Puder, M .
TRANSPLANTATION, 2005, 79 (05) :606-608
[6]   Impact of pan-caspase inhibition in animal models of established steatosis and non-alcoholic steatohepatitis [J].
Anstee, Quentin M. ;
Concas, Danilo ;
Kudo, Hiromi ;
Levene, Adam ;
Pollard, John ;
Charlton, Peter ;
Thomas, Howard C. ;
Thursz, Mark R. ;
Goldin, Robert D. .
JOURNAL OF HEPATOLOGY, 2010, 53 (03) :542-550
[7]   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
[8]  
Atanasova E, 2015, MEDINFORM, V2, P153
[9]   Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis [J].
Athyros, Vasilios G. ;
Tziomalos, Konstantinos ;
Gossios, Thomas D. ;
Griva, Theodora ;
Anagnostis, Panagiotis ;
Kargiotis, Konstantinos ;
Pagourelias, Efstathios D. ;
Theocharidou, Eleni ;
Karagiannis, Asterios ;
Mikhailidis, Dimitri P. .
LANCET, 2010, 376 (9756) :1916-1922
[10]   The pan-caspase inhibitor Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis [J].
Barreyro, Fernando J. ;
Holod, Silvia ;
Finocchietto, Paola V. ;
Camino, Alejandra M. ;
Aquino, Jorge B. ;
Avagnina, Alejandra ;
Carreras, Maria C. ;
Poderoso, Juan J. ;
Gores, Gregory J. .
LIVER INTERNATIONAL, 2015, 35 (03) :953-966