代谢相关脂肪性肝病靶向药物治疗进展

doi:10.3969/j.issn.1004-583X.2023.04.016

摘要/Abstract

摘要：

代谢相关脂肪性肝病的患病率逐年上升,已成为我国最常见的慢性肝脏疾病,严重危害人类健康并对社会造成了巨大的经济负担。目前代谢相关脂肪性肝病的一线治疗主要是改变生活方式和运动锻炼,没有批准的药物疗法。本文对甲状腺激素受体-β激动剂、成纤维细胞生长因子类似物、脂肪酶抑制剂、过氧化物酶体增殖物激活受体激动剂、法尼醇X激活受体激动剂和双重趋化因子受体拮抗剂等新型靶向药物进行综述,以期为代谢相关脂肪性肝病的治疗提供参考。

中图分类号:

R575.5

宗廷妮, 戴光荣, 赵晓宇, 李瑞风, 柴聪敏. 代谢相关脂肪性肝病靶向药物治疗进展[J]. 临床荟萃, 2023, 38(4): 373-376.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2023.04.016

https://huicui.hebmu.edu.cn/CN/Y2023/V38/I4/373

参考文献 31

[1]	Kaya E, Yilmaz Y. Metabolic-associated fatty liver disease (MAFLD): A multi-systemic disease beyond the liver[J]. J Clin Transl Hepatol, 2022, 10(2):329-338. doi: 10.14218/JCTH.2021.00178 pmid: 35528971
[2]	Méndez-Sánchez N, Díaz-Orozco LE. Editorial: International consensus recommendations to replace the terminology of non-Alcoholic fatty liver disease (NAFLD) with metabolic-associated fatty liver disease (MAFLD)[J]. Med Sci Monit, 2021, 27:e933860.
[3]	Xian YX, Weng JP, Xu F. MAFLD vs. NAFLD: Shared features and potential changes in epidemiology, pathophysiology, diagnosis, and pharmacotherapy[J]. Chin Med J (Engl), 2020, 134(1):8-19.
[4]	Harrison SA, Bashir MR, Guy CD, et al. Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: A multicentre, randomised, double-blind, placebo-controlled, phase 2 trial[J]. Lancet, 2019, 394(10213):2012-2024. doi: S0140-6736(19)32517-6 pmid: 31727409
[5]	Harrison SA, Bashir M, Moussa SE, et al. Effects of resmetirom on noninvasive endpoints in a 36-week phase 2 active treatment extension study in patients with NASH[J]. Hepatol Commun, 2021, 5(4):573-588. doi: 10.1002/hep4.1657 pmid: 33860116
[6]	Younossi ZM, Stepanova M, Taub RA, et al. Hepatic fat reduction due to resmetirom in patients with nonalcoholic steatohepatitis is associated with improvement of quality of life[J]. Clin Gastroenterol Hepatol, 2022, 20(6):1354-1361. doi: 10.1016/j.cgh.2021.07.039 URL
[7]	Caddeo A, Kowalik MA, Serra M, et al. TG68, a novel thyroid hormone receptor-β agonist for the treatment of NAFLD[J]. Int J Mol Sci, 2021, 22(23):13105. doi: 10.3390/ijms222313105 URL
[8]	Caddeo A, Serra M, Sedda F, et al. Potential use of TG68-a novel thyromimetic-for the treatment of non-alcoholic fatty liver (NAFLD)-associated hepatocarcinogenesis[J]. Front Oncol, 2023, 13:1127517. doi: 10.3389/fonc.2023.1127517 URL
[9]	Harrison SA, Neff G, Guy CD, et al. Efficacy and safety of aldafermin, an engineered FGF19 analog, in a randomized, double-blind, placebo-controlled trial of patients with nonalcoholic steatohepatitis[J]. Gastroenterology, 2021, 160(1):219-231. doi: 10.1053/j.gastro.2020.08.004 pmid: 32781086
[10]	Harrison SA, Abdelmalek MF, Neff G, et al. Aldafermin in patients with non-alcoholic steatohepatitis (ALPINE 2/3): A randomised, double-blind, placebo-controlled, phase 2b trial[J]. Lancet Gastroenterol Hepatol, 2022, 7(7):603-616. doi: 10.1016/S2468-1253(22)00017-6 URL
[11]	Harrison SA, Ruane PJ, Freilich BL, et al. Efruxifermin in non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled, phase 2a trial[J]. Nat Med, 2021, 27(7):1262-1271. doi: 10.1038/s41591-021-01425-3 pmid: 34239138
[12]	Harrison SA, Ruane PJ, Freilich B, et al. A randomized, double-blind, placebo-controlled phase IIa trial of efruxifermin for patients with compensated NASH cirrhosis[J]. JHEP Rep, 2023, 5(1):100563.
[13]	Sanyal A, Charles ED, Neuschwander-Tetri BA, et al. Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: A randomised, double-blind, placebo-controlled, phase 2a trial[J]. Lancet, 2019, 392(10165):2705-2717. doi: S0140-6736(18)31785-9 pmid: 30554783
[14]	Brown EA, Minnich A, Sanyal AJ, et al. Effect of pegbelfermin on NASH and fibrosis-related biomarkers and correlation with histological response in the FALCON 1 trial[J]. JHEP Rep, 2023, 5(4):100661.
[15]	Alkhouri N, Lawitz E, Noureddin M, et al. GS-0976 (Firsocostat): An investigational liver-directed acetyl-CoA carboxylase (ACC) inhibitor for the treatment of non-alcoholic steatohepatitis (NASH)[J]. Expert Opin Investig Drugs, 2020, 29(2):135-141. doi: 10.1080/13543784.2020.1668374 URL
[16]	Calle RA, Amin NB, Carvajal-Gonzalez S, et al. ACC inhibitor alone or co-administered with a DGAT2 inhibitor in patients with non-alcoholic fatty liver disease: Two parallel, placebo-controlled, randomized phase 2a trials[J]. Nat Med, 2021, 27(10):1836-1848. doi: 10.1038/s41591-021-01489-1 pmid: 34635855
[17]	Syed-Abdul MM, Parks EJ, Gaballah AH, et al. Fatty acid synthase inhibitor TVB-2640 reduces hepatic de novo lipogenesis in males with metabolic abnormalities[J]. Hepatology, 2020, 72(1):103-118. doi: 10.1002/hep.31000 pmid: 31630414
[18]	Loomba R, Mohseni R, Lucas KJ, et al. TVB-2640 (FASN Inhibitor) for the treatment of nonalcoholic steatohepatitis: FASCINATE-1, a randomized, placebo-controlled phase 2a trial[J]. Gastroenterology, 2021, 161(5):1475-1486. doi: 10.1053/j.gastro.2021.07.025 pmid: 34310978
[19]	Fernández-Ramos D, Lopitz-Otsoa F, Delacruz-Villar L, et al. Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation[J]. World J Gastroenterol, 2020, 26(34):5101-5117. doi: 10.3748/wjg.v26.i34.5101 URL
[20]	Ratziu V, de Guevara L, Safadi R, et al. Aramchol in patients with nonalcoholic steatohepatitis: A randomized, double-blind, placebo-controlled phase 2b trial[J]. Nat Med, 2021, 27(10):1825-1835. doi: 10.1038/s41591-021-01495-3 pmid: 34621052
[21]	Loomba R, Morgan E, Watts L, et al. Novel antisense inhibition of diacylglycerol O-acyltransferase 2 for treatment of non-alcoholic fatty liver disease: A multicentre, double-blind, randomised, placebo-controlled phase 2 trial[J]. Lancet Gastroenterol Hepatol, 2020, 5(9):829-838. doi: 10.1016/S2468-1253(20)30186-2 URL
[22]	Akbari R, Behdarvand T, Afarin R, et al. Saroglitazar improved hepatic steatosis and fibrosis by modulating inflammatory cytokines and adiponectin in an animal model of non-alcoholic steatohepatitis[J]. BMC Pharmacol Toxicol, 2021, 22(1):53. doi: 10.1186/s40360-021-00524-8
[23]	Gawrieh S, Noureddin M, Loo N, et al. Saroglitazar, a PPAR-α/γ Agonist, for treatment of NAFLD: A randomized controlled double-blind phase 2 trial[J]. Hepatology, 2021, 74(4):1809-1824. doi: 10.1002/hep.31843 pmid: 33811367
[24]	Padole P, Arora A, Sharma P, et al. Saroglitazar for nonalcoholic fatty liver disease: A single centre experience in 91 patients[J]. J Clin Exp Hepatol, 2022, 12(2):435-439. doi: 10.1016/j.jceh.2021.06.015 URL
[25]	Younossi ZM, Ratziu V, Loomba R, et al. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: Interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial[J]. Lancet, 2019, 394(10215):2184-2196. doi: S0140-6736(19)33041-7 pmid: 31813633
[26]	Younossi ZM, Stepanova M, Nader F, et al. Obeticholic acid impact on quality of life in patients with nonalcoholic steatohepatitis: REGENERATE 18-month interim analysis[J]. Clin Gastroenterol Hepatol, 2022, 20(9):2050-2058. doi: 10.1016/j.cgh.2021.07.020 URL
[27]	Patel K, Harrison SA, Elkhashab M, et al. Cilofexor, a nonsteroidal FXR agonist, in patients with noncirrhotic NASH: A phase 2 randomized controlled trial[J]. Hepatology, 2020, 72(1):58-71. doi: 10.1002/hep.31205 pmid: 32115759
[28]	Alkhouri N, Herring R, Kabler H, et al. 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]. J Hepatol, 2022, 77(3):607-618. doi: 10.1016/j.jhep.2022.04.003 URL
[29]	Harrison SA, Bashir MR, Lee KJ, et al. A structurally optimized FXR agonist, MET409, reduced liver fat content over 12 weeks in patients with non-alcoholic steatohepatitis[J]. J Hepatol, 2021, 75(1):25-33. doi: 10.1016/j.jhep.2021.01.047 pmid: 33581174
[30]	Friedman SL, Ratziu V, Harrison SA, et al. A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis[J]. Hepatology, 2018, 67(5):1754-1767. doi: 10.1002/hep.29477 pmid: 28833331
[31]	Ratziu V, Sanyal A, Harrison SA, et al. Cenicriviroc treatment for adults with nonalcoholic steatohepatitis and fibrosis: Final analysis of the phase 2b CENTAUR study[J]. Hepatology, 2020, 72(3):892-905. doi: 10.1002/hep.31108 URL

代谢相关脂肪性肝病靶向药物治疗进展

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献 31

相关文章 15

编辑推荐

Metrics

本文评价

[1]	张娜文, 黄少敏, 田利民. 2型糖尿病与帕金森病相关性研究的进展[J]. 临床荟萃, 2023, 38(9): 845-850.
[2]	郭文惠, 雷皓月, 潘友卓, 张琦. 质膜膜泡关联蛋白的生物学功能研究进展[J]. 临床荟萃, 2023, 38(7): 647-653.
[3]	杨小雄, 杨帆, 魏小果. 肠-微生物群-肝轴与代谢相关脂肪性肝病的研究进展[J]. 临床荟萃, 2023, 38(6): 559-563.
[4]	刘亚鑫, 郭岚, 王泽凯, 牛凯. 慢性肾脏病合并骨质疏松症治疗的研究进展[J]. 临床荟萃, 2023, 38(12): 1146-1149.
[5]	张莉敏, 孙军. FIB-4在代谢相关脂肪性肝病合并结直肠腺瘤性息肉患者的预测价值[J]. 临床荟萃, 2022, 37(4): 334-338.
[6]	罗方林, 官素英, 吴国祥. 沙库巴曲缬沙坦钠联合新活素治疗急性左心衰竭的疗效[J]. 临床荟萃, 2021, 36(9): 782-785.
[7]	周耀, 魏博涛, 沈阳. 人腺病毒感染的药物治疗新进展[J]. 临床荟萃, 2021, 36(7): 669-672.
[8]	卢昊阳, 卢家忠, 韩明锋, 吕新才, 张标, 戎成振, 贾蕾蕾, 潘强强, 马蕾蕾, 赵韧. 新型冠状病毒肺炎合并心血管疾病的临床治疗观察[J]. 临床荟萃, 2021, 36(3): 203-207.
[9]	高兴连, 童宗武, 杨崇猛, 赵艳红, 卢永新, 丁蓉. 序贯化疗系统性免疫球蛋白轻链型淀粉样变性肾病1例[J]. 临床荟萃, 2021, 36(3): 266-269.
[10]	王艳军, 崔炜. 降压治疗中低血压的成因及处理[J]. 临床荟萃, 2021, 36(3): 270-276.
[11]	张佳红，周淑红，周静，王慧娟. 沙利度胺治疗结缔组织病相关肺间质疾病的临床观察[J]. 临床荟萃, 2019, 34(7): 622-625.
[12]	贝丽叶1, 2，史玉叶1, 2，王春玲1, 2. 来那度胺在复发难治性非霍奇金B细胞淋巴瘤治疗中的应用[J]. 临床荟萃, 2019, 34(6): 508-513.
[13]	林晓红1，2，李鸿茹2, 3，陈愉生2，3，林丹2，陈诗杰2，谢剑峰4. 三甲医院重症社区获得性肺炎治疗现状分析[J]. 临床荟萃, 2019, 34(2): 132-135.
[14]	刘雪梅，张昌红，刘晓静. 服阿奇霉素联合噻托溴铵粉吸入剂治疗支气管扩张伴阻塞性通气功能障碍患者的疗效观察[J]. 临床荟萃, 2018, 33(9): 805-807.
[15]	Ted Wu1，刘珊2，许樟荣3. 糖尿病药物治疗新进展[J]. 临床荟萃, 2017, 32(8): 654-657.