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非酒精性脂肪性肝炎新药研发:一个未被满足的临床需求

何忆宁 施军平

引用本文:
Citation:

非酒精性脂肪性肝炎新药研发:一个未被满足的临床需求

DOI: 10.3969/j.issn.1001-5256.2021.06.001
基金项目: 

杭州市重大科技计划项目 (20172016A03)

利益冲突声明:所有作者均声明不存在利益冲突。
作者贡献声明:何忆宁负责完成述评初稿撰写;施军平负责设计文章思路,初稿修订,审核及定稿。
详细信息
    作者简介:

    何忆宁(1996—),女,主要从事非酒精性脂肪性肝病的临床研究

    通信作者:

    施军平,20131004@hznu.edu.cn

  • 中图分类号: R575.5

Research and development of new drugs for nonalcoholic steatohepatitis: An unmet need in clinical practice

  • 摘要: 随着全球范围内病毒性肝炎得到有效控制,非酒精性脂肪性肝炎(NASH)在未来10年将成为肝移植的主要病因。NASH患者数量庞大,但至今尚无任何权威机构批准的治疗药物上市,这代表着一个巨大的尚未满足的临床需求。NASH复杂的发病机制、疾病异质性、诊断障碍以及治疗终点的选择等给新药研发带来了巨大挑战。

     

  • [1] YOUNOSSI Z, ANSTEE QM, MARIETTI M, et al. Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention[J]. Nat Rev Gastroenterol Hepatol, 2018, 15(1): 11-20. DOI: 10.1038/nrgastro.2017.109.
    [2] LUDWIG J, VIGGIANO TR, MCGILL DB, et al. Nonalcoholic steatohepatitis: Mayo clinic experiences with a hitherto unnamed disease[J]. Mayo Clin Proc, 1980, 55(7): 434-438.
    [3] 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.
    [4] RATZIU V, SANYAL AJ, LOOMBA R, et al. REGENERATE: Design of a pivotal, randomised, phase 3 study evaluating the safety and efficacy of obeticholic acid in patients with fibrosis due to nonalcoholic steatohepatitis[J]. Contemp Clin Trials, 2019, 84: 105803. DOI: 10.1016/j.cct.2019.06.017.
    [5] DAVID D, EAPEN CE. What are the current pharmacological therapies for nonalcoholic fatty liver disease?[J]. J Clin Exp Hepatol, 2021, 11(2): 232-238. DOI: 10.1016/j.jceh.2020.09.001.
    [6] ANANIA FA, DIMICK-SANTOS L, MEHTA R, et al. Nonalcoholic steatohepatitis: Current thinking from the division of hepatology and nutrition at the Food and Drug Administration[J]. Hepatology, 2021, 73(5): 2023-2027. DOI: 10.1002/hep.31687.
    [7] GOULART E, de CAIRES-JUNIOR LC, TELLES-SILVA KA, et al. 3D bioprinting of liver spheroids derived from human induced pluripotent stem cells sustain liver function and viability in vitro[J]. Biofabrication, 2019, 12(1): 015010. DOI: 10.1088/1758-5090/ab4a30.
    [8] 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[J]. Gastroenterology, 2016, 150(5): 1147-1159. e5. DOI: 10.1053/j.gastro.2016.01.038.
    [9] SHARMA M, PREMKUMAR M, KULKARNI AV, et al. Drugs for non-alcoholic steatohepatitis (NASH): Quest for the holy grail[J]. J Clin Transl Hepatol, 2021, 9(1): 40-50. DOI: 10.14218/JCTH.2020.00055.
    [10] KIM W, KIM BG, LEE JS, et al. Randomised clinical trial: The efficacy and safety of oltipraz, a liver X receptor alpha-inhibitory dithiolethione in patients with non-alcoholic fatty liver disease[J]. Aliment Pharmacol Ther, 2017, 45(8): 1073-1083. DOI: 10.1111/apt.13981.
    [11] ALKHOURI N. Thyromimetics as emerging therapeutic agents for nonalcoholic steatohepatitis: Rationale for the development of resmetirom (MGL-3196)[J]. Expert Opin Investig Drugs, 2020, 29(2): 99-101. DOI: 10.1080/13543784.2020.1708899.
    [12] HARRISON SA, ROSSI SJ, PAREDES AH, et al. NGM282 improves liver fibrosis and histology in 12 weeks in patients with nonalcoholic steatohepatitis[J]. Hepatology, 2020, 71(4): 1198-1212. DOI: 10.1002/hep.30590.
    [13] GENG L, LAM K, XU A. The therapeutic potential of FGF21 in metabolic diseases: From bench to clinic[J]. Nat Rev Endocrinol, 2020, 16(11): 654-667. DOI: 10.1038/s41574-020-0386-0.
    [14] 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: 10.1016/S0140-6736(18)31785-9.
    [15] SAFADI R, KONIKOFF FM, MAHAMID M, et al. The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease[J]. Clin Gastroenterol Hepatol, 2014, 12(12): 2085-2091. e1. DOI: 10.1016/j.cgh.2014.04.038.
    [16] 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[J]. Lancet, 2016, 387(10019): 679-690. DOI: 10.1016/S0140-6736(15)00803-X.
    [17] NEWSOME PN, BUCHHOLTZ K, CUSI K, et al. A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis[J]. N Engl J Med, 2021, 384(12): 1113-1124. DOI: 10.1056/NEJMoa2028395.
    [18] SHIMIZU M, SUZUKI K, KATO K, et al. Evaluation of the effects of dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on hepatic steatosis and fibrosis using transient elastography in patients with type 2 diabetes and non-alcoholic fatty liver disease[J]. Diabetes Obes Metab, 2019, 21(2): 285-292. DOI: 10.1111/dom.13520.
    [19] JEONG SW. Nonalcoholic fatty liver disease: A drug revolution is coming[J]. Diabetes Metab J, 2020, 44(5): 640-657. DOI: 10.4093/dmj.2020.0115.
    [20] INOUE M, HAYASHI A, TAGUCHI T, et al. Effects of canagliflozin on body composition and hepatic fat content in type 2 diabetes patients with non-alcoholic fatty liver disease[J]. J Diabetes Investig, 2019, 10(4): 1004-1011. DOI: 10.1111/jdi.12980.
    [21] KITAZAWA M, KATAGIRI T, SUZUKI H, et al. A 52-week randomized controlled trial of ipragliflozin or sitagliptin in type 2 diabetes combined with metformin: The N-ISM study[J]. Diabetes Obes Metab, 2021, 23(3): 811-821. DOI: 10.1111/dom.14288.
    [22] ZHAO Q, LIU J, DENG H, et al. Targeting mitochondria-located circRNA SCAR alleviates NASH via reducing mros output[J]. Cell, 2020, 183(1): 76-93. e22. DOI: 10.1016/j.cell.2020.08.009.
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  • 收稿日期:  2021-05-04
  • 录用日期:  2021-05-04
  • 出版日期:  2021-06-20
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