非酒精性脂肪性肝病治疗研究进展

doi:10.3969/j.issn.1672-5069.2019.01.038

摘要/Abstract

摘要： 非酒精性脂肪性肝病是全球性的公共卫生问题。调整生活方式及保持健康心理状态是治疗非酒精性脂肪性肝病的基础。本文通过对其发病机理研究的梳理,重点介绍了近年来国内外关于非酒精性脂肪性肝病药物治疗的进展,包括氧化应激、炎症反应、脂质代谢、纤维形成和细胞凋亡等不同阶段靶向治疗药物应用的安全性和有效性。

关键词: 非酒精性脂肪性肝病, 氧化应激, 治疗

Abstract: Non-alcoholic fatty liver disease（NAFLD） is a global public health problem. Adjusting lifestyle and maintaining a healthy mental state are the cornerstones in dealing with patients with NAFLD. This article focuses on the recent progress at home and abroad in medical treatment of NAFLD and reviews the safety and efficacy of targeted therapies in different stages of oxidative stress,inflammatory response,lipid metabolism,fibrogenesis,and apoptosis.

Key words: Nonalcoholic fatty liver diseases, Oxidative stress, Treatment

钟燕, 苏淑婷综述, 宓余强审校. 非酒精性脂肪性肝病治疗研究进展[J]. 实用肝脏病杂志, 2019, 22(1): 145-148.

Zhong Yan, Su Shuting, Mi Yuqiang.. Treatment of patients with nonalcoholic fatty liver disease[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(1): 145-148.

参考文献

[1] Panasevich MR,Meers GM,Linden MA,et al.High fat,high fructose,high cholesterol feeding causes severe NASH and cecal microbiota dysbiosis in juvenile ossabaw swine. Am J Physiol Endocrinol Metab,2017,341(1):E78-E92.
[2] Al-Gayyar MM,Shams ME,Barakat EA.Fish oil improves lipid metabolism and ameliorates inflammation in patients with metabolic syndrome:impact of nonalcoholic fatty liver disease. Pharm Biol,2012,50(3):297-303.
[3] Nakamura M,Suetsugu A,Hasegawa K,et al.Choline-efficient-diet-induced fatty liver is a metastasis-resistant microenviron-ment. Anticancer Res,2017,37(7):3429-3434.
[4] Zhai X,Ren D,Luo Y,et al.Chemical characteristics of an Ilex Kuding tea polysaccharide and its protective effects against high fructose-induced liver injury and vascular endothelial dysfunction in mice. Food Funct,2017,8(7):2536-2547.
[5] Johnson S,Koh WP,Wang R,et al.Coffee consumption and reduced risk of hepatocellular carcinoma: findings from the Singapore Chinese Health Study.Cancer Causes Control,2011,22(3):503-510.
[6] Mokhtari Z,Gibson DL,Hekmatdoost A.Nonalcoholic fatty liver disease,the gut microbiome,and diet. Adv Nutr,2017,8(2):240-252.
[7] Zhang HJ,He J,Pan LL,et al.Effects of moderate and vigorous exercise on nonalcoholic fatty liver disease:A randomized clinical trial. JAMA Intern Med,2016,176(8):1074-1082.
[8] Oh S,So R,Shida T,et al.High-intensity aerobic exercise improves both hepatic fat content and stiffness in sedentary obese men with nonalcoholic fatty liver disease.Sci Rep,2017,7:43029.
[9] Hashida R,Kawaguchi T,Bekki M,et al.Aerobic vs resistance exercise in non-alcoholic fatty liver disease:A systematic review. J Hepatol,2017,66(1):142-152.
[10] Oh S,Shida T,Yamagishi K,et al.Moderate to vigorous physical activity volume is an important factor for managing nonalcoholic fatty liver disease:a retrospective study. Hepatology,2015,61(4):1205-1215.
[11] Katsagoni CN,Georgoulis M,Papatheodoridis GV,et al.Effects of lifestyle interventions on clinical characteristics of patients with non-alcoholic fatty liver disease:A meta-analysis.Metabolism,2017, 68:119-132.
[12] Youssef NA,Abdelmalek MF,Binks M,etal. Associations of depression,anxiety and antidepressants with histological severity of nonalcoholic fatty liver disease. Liver Int,2013,33(7):1062-1070.
[13] Alcala M,Calderon-Dominguez M,Serra D,et al.Short-term vitamin E treatment impairs reactive oxygen species signaling required for adipose tissue expansion,resulting in fatty liver and insulin resistance in obese mice. PLoS One,2017,12(10):e0186579.
[14] Lavine JE,Schwimmer JB,Van Natta ML,et al.Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents:the TONIC randomized controlled trial.JAMA,2011,305(16):1659-1668.
[15] Chalasani N,Younossi Z,Lavine JE,et al.The diagnosis and management of nonalcoholic fatty liver disease:Practice guidance from the American Association for the Study of Liver Diseases. Hepatology,2018,67(1):328-357.
[16] Lippman SM,Klein EA,Goodman PJ,et al.Effect of selenium and vitamin E on risk of prostate cancer and other cancers:the selenium and vitamin E cancer prevention trial (SELECT).JAMA,2009,301(1):39-51.
[17] Okada Y,Yamaguchi K,Nakajima T,et al.Rosuvastatin ameliorates high-fat and high-cholesterol diet-induced nonalcoholic steatohepatitis in rats. Liver Int,2013,33(2):301-311.
[18] Athyros VG,Mikhailidis DP,Didangelos TP,et al.Effect of multifactorial treatment on non-alcoholic fatty liver disease in metabolic syndrome:a randomised study. Curr Med Res Opin,2006,22(5):873-883.
[19] Lefebvre E,Moyle G,Reshef R,et al.Antifibrotic effects of the dual CCR2/CCR5 antagonist cenicriviroc in animal models of liver and kidney fibrosis.PLoS One,2016,11(6):e0158156.
[20] Friedman SL,Ratziu V,Harrison SA,et al.A randomized,placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis.Hepatology,2017,294:77.
[21] Liss KH,Finck BN.PPARs and nonalcoholic fatty liver disease. Biochimie,2017,136:65-74.
[22] Ratziu V,Harrison SA,Francque S,et al.Elafibranor,an agonist of the peroxisome proliferator-activated receptor-α and-δ,induces resolution of nonalcoholic steatohepatitis without fibrosis worsening. Gastroenterology,2016,150(5):1147-1159.
[23] Geier A,Rau M.Emerging therapies for NASH-the future is now. Expert Rev Clin Pharmacol,2017,10(5):467-469.
[24] Fang S,Suh JM,Reilly SM,et al.Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat Med,2015,21(2):159-165.
[25] Neuschwander-Tetri BA,Loomba R,Sanyal AJ,et al.Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic,non-alcoholic steatohepatitis(FLINT):a multicentre,randomised, placebo-controlled trial.Lancet,2015,385(9972):956-965.
[26] Armstrong LE,Guo GL.Role of FXR in liver inflammation during nonalcoholic steatohepatitis. Curr Pharmacol Rep,2017,3(2):92-100.
[27] Armstrong MJ,Hull D,Guo K,et al.Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis. J Hepatol,2016,64(2):399-408.
[28] Pi-Sunyer X,Astrup A,Fujioka K,et al.A randomized,controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med,2015,373(1):11-22.
[29] He Q,Sha S,Sun L,et al.GLP-1 analogue improves hepatic lipid accumulation by inducing autophagy via AMPK/mTOR pathway. Biochem Biophys Res Commun,2016,476(4):196-203.
[30] Armstrong MJ,Gaunt P,Aithal GP,et al.Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN):a multicentre,double-blind,randomised,placebo-controlled phase 2 study.Lancet,2016,387(10019):679-690.