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非酒精性脂肪肝病的治疗模式和潜在疗法

李凤 李茂微 王雨杉

引用本文:
Citation:

非酒精性脂肪肝病的治疗模式和潜在疗法

DOI: 10.12449/JCH241025
基金项目: 

吉林省科技厅项目 (20210401054YY)

利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:李凤负责资料分析与撰写论文并最终定稿;李茂微、王雨杉协助收集资料并修改论文。
详细信息
    通信作者:

    李凤, 18943994025@163.com (ORCID: 0009-0009-8760-3675)

Therapeutic paradigms and potential therapies for nonalcoholic steatohepatitis

Research funding: 

Jilin Provincial Department of Science and Technology Project (20210401054YY)

More Information
  • 摘要: 近年来,非酒精性脂肪性肝炎(NASH)在流行病学、发病机理和确定治疗靶点等方面取得了稳步进展,但在治疗药物开发领域却进展缓慢。本文综述了生活方式干预、手术方法、肠道微生物群和药物治疗在治疗NASH方面的进展,重点关注胰岛素增敏剂、抗氧化剂、降胆固醇药物、甲状腺激素类似物、肠促胰岛素和细胞因子等药物对治疗NASH的作用,以期为未来治疗NASH提供更多的方法和选择。

     

  • [1] ZEIGERER A. NAFLD-A rising metabolic disease[J]. Mol Metab, 2021, 50: 101274. DOI: 10.1016/j.molmet.2021.101274.
    [2] WANG YK, WEI SY, LIU C, et al. A new definition of fatty liver disease: from nonalcoholic fatty liver disease to metabolic associated fatty liver disease[J]. Chin J Dig Surg, 2023, 22( S1): 117- 121. DOI: 10.3760/cma.j.cn115610-20230909-00080.

    王永康, 魏诗雨, 刘昌, 等. 脂肪性肝病新定义:从非酒精性脂肪性肝病到代谢功能障碍相关脂肪性肝病[J]. 中华消化外科杂志, 2023, 22( S1): 117- 121. DOI: 10.3760/cma.j.cn115610-20230909-00080.
    [3] DUELL PB, WELTY FK, MILLER M, et al. Nonalcoholic fatty liver disease and cardiovascular risk: A scientific statement from the American heart association[J]. Arterioscler Thromb Vasc Biol, 2022, 42( 6): e168- e185. DOI: 10.1161/ATV.0000000000000153.
    [4] CIARDULLO S, BALLABENI C, TREVISAN R, et al. Liver stiffness, albuminuria and chronic kidney disease in patients with NAFLD: A systematic review and meta-analysis[J]. Biomolecules, 2022, 12( 1): 105. DOI: 10.3390/biom12010105.
    [5] BJÖRKSTRÖM K, WIDMAN L, HAGSTRÖM H. Risk of hepatic and extrahepatic cancer in NAFLD: A population-based cohort study[J]. Liver Int, 2022, 42( 4): 820- 828. DOI: 10.1111/liv.15195.
    [6] ESTES C, ANSTEE QM, ARIAS-LOSTE MT, et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030[J]. J Hepatol, 2018, 69( 4): 896- 904. DOI: 10.1016/j.jhep.2018.05.036.
    [7] POUWELS S, SAKRAN N, GRAHAM Y, et al. Non-alcoholic fatty liver disease(NAFLD): A review of pathophysiology, clinical management and effects of weight loss[J]. BMC Endocr Disord, 2022, 22( 1): 63. DOI: 10.1186/s12902-022-00980-1.
    [8] HYDES TJ, RAVI S, LOOMBA R, et al. Evidence-based clinical advice for nutrition and dietary weight loss strategies for the management of NAFLD and NASH[J]. Clin Mol Hepatol, 2020, 26( 4): 383- 400. DOI: 10.3350/cmh.2020.0067.
    [9] YOUNOSSI ZM, COREY KE, LIM JK. AGA clinical practice update on lifestyle modification using diet and exercise to achieve weight loss in the management of nonalcoholic fatty liver disease: Expert review[J]. Gastroenterology, 2021, 160( 3): 912- 918. DOI: 10.1053/j.gastro.2020.11.051.
    [10] HANNAH WN Jr, HARRISON SA. Effect of weight loss, diet, exercise, and bariatric surgery on nonalcoholic fatty liver disease[J]. Clin Liver Dis, 2016, 20( 2): 339- 350. DOI: 10.1016/j.cld.2015.10.008.
    [11] SUN J, RUAN YT, XU NN, et al. The effect of dietary carbohydrate and calorie restriction on weight and metabolic health in overweight/obese individuals: A multi-center randomized controlled trial[J]. BMC Med, 2023, 21( 1): 192. DOI: 10.1186/s12916-023-02869-9.
    [12] WEI XY, LIN BQ, HUANG Y, et al. Effects of time-restricted eating on nonalcoholic fatty liver disease: The TREATY-FLD randomized clinical trial[J]. JAMA Netw Open, 2023, 6( 3): e233513. DOI: 10.1001/jamanetworkopen.2023.3513.
    [13] CASTAGNETO-GISSEY L, CASELLA-MARIOLO J, MINGRONE G. Bariatric/metabolic surgery[J]. Handb Exp Pharmacol, 2022, 274: 371- 386. DOI: 10.1007/164_2021_565.
    [14] VERRASTRO O, PANUNZI S, CASTAGNETO-GISSEY L, et al. Bariatric-metabolic surgery versus lifestyle intervention plus best medical care in non-alcoholic steatohepatitis(BRAVES): A multicentre, open-label, randomised trial[J]. Lancet, 2023, 401( 10390): 1786- 1797. DOI: 10.1016/S0140-6736(23)00634-7.
    [15] TILG H, ADOLPH TE, TRAUNER M. Gut-liver axis: Pathophysiological concepts and clinical implications[J]. Cell Metab, 2022, 34( 11): 1700- 1718. DOI: 10.1016/j.cmet.2022.09.017.
    [16] LIU LL, ZHANG JH, CHENG Y, et al. Gut microbiota: A new target for T2DM prevention and treatment[J]. Front Endocrinol(Lausanne), 2022, 13: 958218. DOI: 10.3389/fendo.2022.958218.
    [17] ALVES CC, WAITZBERG DL, de ANDRADE LS, et al. Prebiotic and synbiotic modifications of beta oxidation and lipogenic gene expression after experimental hypercholesterolemia in rat liver[J]. Front Microbiol, 2017, 8: 2010. DOI: 10.3389/fmicb.2017.02010.
    [18] XUE LF, DENG ZL, LUO WH, et al. Effect of fecal microbiota transplantation on non-alcoholic fatty liver disease: A randomized clinical trial[J]. Front Cell Infect Microbiol, 2022, 12: 759306. DOI: 10.3389/fcimb.2022.759306.
    [19] SAKURAI Y, KUBOTA N, YAMAUCHI T, et al. Role of insulin resistance in MAFLD[J]. Int J Mol Sci, 2021, 22( 8): 4156. DOI: 10.3390/ijms22084156.
    [20] BELL DSH, JERKINS T. In praise of pioglitazone: An economically efficacious therapy for type 2 diabetes and other manifestations of the metabolic syndrome[J]. Diabetes Obes Metab, 2023, 25( 11): 3093- 3102. DOI: 10.1111/dom.15222.
    [21] LEWIS J, HABEL L, QUESENBERRY C, et al. Pioglitazone use and risk of bladder cancer and other common cancers in persons with diabetes[J]. JAMA, 2015, 314( 3): 265- 77. DOI: 10.1001/jama.2015.7996.
    [22] WABITSCH S, MCCALLEN JD, KAMENYEVA O, et al. Metformin treatment rescues CD8+ T-cell response to immune checkpoint inhibitor therapy in mice with NAFLD[J]. J Hepatol, 2022, 77( 3): 748- 760. DOI: 10.1016/j.jhep.2022.03.010.
    [23] HARRISON SA, ALKHOURI N, DAVISON BA, et al. Insulin sensitizer MSDC-0602K in non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled phase IIb study[J]. J Hepatol, 2020, 72( 4): 613- 626. DOI: 10.1016/j.jhep.2019.10.023.
    [24] CHEN Z, TIAN RF, SHE ZG, et al. Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease[J]. Free Radic Biol Med, 2020, 152: 116- 141. DOI: 10.1016/j.freeradbiomed.2020.02.025.
    [25] NAGASHIMADA M, OTA T. Role of vitamin E in nonalcoholic fatty liver disease[J]. IUBMB Life, 2019, 71( 4): 516- 522. DOI: 10.1002/iub.1991.
    [26] SANYAL AJ, CHALASANI N, KOWDLEY KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis[J]. N Engl J Med, 2010, 362( 18): 1675- 1685. DOI: 10.1056/NEJMoa0907929.
    [27] LOH WQ, YOUN J, SEOW WJ. Vitamin E intake and risk of prostate cancer: A meta-analysis[J]. Nutrients, 2022, 15( 1): 14. DOI: 10.3390/nu15010014.
    [28] ĆULAFIĆ M, VEZMAR-KOVAČEVIĆ S, DOPSAJ V, et al. Pentoxifylline with metformin treatment improves biochemical parameters in patients with nonalcoholic steatohepatitis[J]. J Med Biochem, 2020, 39( 3): 290- 298. DOI: 10.2478/jomb-2019-0043.
    [29] ZHU XX, WU M, WANG H, et al. Safety, tolerability, and pharmacokinetics of the novel pan-phosphodiesterase inhibitor ZSP1601 in healthy subjects: A double-blinded, placebo-controlled first-in-human single-dose and multiple-dose escalation and food effect study[J]. Expert Opin Investig Drugs, 2021, 30( 5): 579- 589. DOI: 10.1080/13543784.2021.1900822.
    [30] HU Y, LI HJ, ZHANG H, et al. ZSP1601, a novel pan-phosphodiesterase inhibitor for the treatment of NAFLD, A randomized, placebo-controlled phase Ib/IIa trial[J]. Nat Commun, 2023, 14( 1): 6409. DOI: 10.1038/s41467-023-42162-0.
    [31] 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. e 1. DOI: 10.1016/j.cgh.2014.04.038.
    [32] MALIK A, NADEEM M, AMJAD W, et al. Effects of Aramchol in patients with nonalcoholic fatty liver disease(NAFLD). A systematic review and meta-analysis[J]. Prz Gastroenterol, 2023, 18( 1): 67- 75. DOI: 10.5114/pg.2022.113573.
    [33] WANG CE, XU WT, GONG J, et al. Research progress on the treatment of non-alcoholic fatty liver disease[J]. Clin J Med Offic, 2022, 50( 9): 897- 899, 903. DOI: 10.16680/j.1671-3826.2022.09.06.

    王彩娥, 许文涛, 宫建, 等. 非酒精性脂肪性肝病治疗研究进展[J]. 临床军医杂志, 2022, 50( 9): 897- 899, 903. DOI: 10.16680/j.1671-3826.2022.09.06.
    [34] KANNT A, WOHLFART P, MADSEN AN, et al. Activation of thyroid hormone receptor-β improved disease activity and metabolism independent of body weight in a mouse model of non-alcoholic steatohepatitis and fibrosis[J]. Br J Pharmacol, 2021, 178( 12): 2412- 2423. DOI: 10.1111/bph.15427.
    [35] MAVROMATI M, JORNAYVAZ FR. Hypothyroidism-associated dyslipidemia: Potential molecular mechanisms leading to NAFLD[J]. Int J Mol Sci, 2021, 22( 23): 12797. DOI: 10.3390/ijms222312797.
    [36] HU LY, GU YP, LIANG J, et al. Discovery of highly potent and selective thyroid hormone receptor β agonists for the treatment of nonalcoholic steatohepatitis[J]. J Med Chem, 2023, 66( 5): 3284- 3300. DOI: 10.1021/acs.jmedchem.2c01669.
    [37] KARIM G, BANSAL MB. Resmetirom: An orally administered, smallmolecule, liver-directed, β-selective THR agonist for the treatment of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis[J]. touchREV Endocrinol, 2023, 19( 1): 60- 70. DOI: 10.17925/EE.2023.19.1.60.
    [38] HARRISON SA, BEDOSSA P, GUY CD, et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis[J]. N Engl J Med, 2024, 390( 6): 497- 509. DOI: 10.1056/NEJMoa2309000.
    [39] LOOMBA R, NEUTEL J, BERNARD D, et al. VK2809, a novel liver-directed thyroid receptor beta agonist, significantly reduces liver fat in patients with non-alcoholic fatty liver disease: a phase 2 randomized, placebo-controlled trial[J]. Hepatology, 2018,( 6): 68. DOI: 10.1016/s0168-8278(20)30652-8.
    [40] LI QX, GAO H, GUO YX, et al. GLP-1 and underlying beneficial actions in Alzheimer’s disease, hypertension, and NASH[J]. Front Endocrinol, 2021, 12: 721198. DOI: 10.3389/fendo.2021.721198.
    [41] BERNSMEIER C, MEYER-GERSPACH AC, BLASER LS, et al. Glucose-induced glucagon-like Peptide 1 secretion is deficient in patients with non-alcoholic fatty liver disease[J]. PLoS One, 2014, 9( 1): e87488. DOI: 10.1371/journal.pone.0087488.
    [42] 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.
    [43] JASTREBOFF AM, KAPLAN LM, FRÍAS JP, et al. Triple-hormone-receptor agonist retatrutide for obesity- A phase 2 trial[J]. N Engl J Med, 2023, 389( 6): 514- 526. DOI: 10.1056/NEJMoa2301972.
    [44] DUAN YM, PAN XF, LUO JY, et al. Association of inflammatory cytokines with non-alcoholic fatty liver disease[J]. Front Immunol, 2022, 13: 880298. DOI: 10.3389/fimmu.2022.880298.
    [45] FONTES-CAL TCM, MATTOS RT, MEDEIROS NI, et al. Crosstalk between plasma cytokines, inflammation, and liver damage as a new strategy to monitoring NAFLD progression[J]. Front Immunol, 2021, 12: 708959. DOI: 10.3389/fimmu.2021.708959.
    [46] ALAAEDDINE N, SIDAOUI J, HILAL G, et al. TNF-α messenger ribonucleic acid(mRNA) in patients with nonalcoholic steatohepatitis[J]. Eur Cytokine Netw, 2012, 23( 3): 107- 111. DOI: 10.1684/ecn.2012.0313.
    [47] AHMED H, UMAR MI, IMRAN S, et al. TGF-β1 signaling can worsen NAFLD with liver fibrosis backdrop[J]. Exp Mol Pathol, 2022, 124: 104733. DOI: 10.1016/j.yexmp.2021.104733.
    [48] WIDJAJA AA, SINGH BK, ADAMI E, et al. Inhibiting interleukin 11 signaling reduces hepatocyte death and liver fibrosis, inflammation, and steatosis in mouse models of nonalcoholic steatohepatitis[J]. Gastroenterology, 2019, 157( 3): 777- 792. e 14. DOI: 10.1053/j.gastro.2019.05.002.
    [49] ANSTEE QM, NEUSCHWANDER-TETRI BA, WAI-SUN WONG V, et al. Cenicriviroc lacked efficacy to treat liver fibrosis in nonalcoholic steatohepatitis: AURORA phase Ⅲ randomized study[J]. Clin Gastroenterol Hepatol, 2024, 22( 1): 124- 134. e 1. DOI: 10.1016/j.cgh.2023.04.003.
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  • 收稿日期:  2024-02-21
  • 录用日期:  2024-03-26
  • 出版日期:  2024-10-25
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