白细胞在非酒精性脂肪性肝病发生及进展中的作用

摘要/Abstract

摘要： 非酒精性脂肪性肝病(NAFLD)的患病率越来越高,已成为我国乃至全球最常见的慢性肝病,NAFLD可由单纯性脂肪肝进展至非酒精性脂肪性肝炎(NASH),甚至肝硬化和肝癌,严重影响人类身体健康,但是NAFLD的发病机制尚未完全明确,而且目前尚无可靠且有效的治疗药物,故研究NAFLD发病机制具有十分重要的意义,而白细胞在NAFLD发生及进展中的重要作用也被越来越多的研究揭示。本文就白细胞及其主要亚类中性粒细胞、单核-巨噬细胞、B淋巴细胞、T淋巴细胞在NAFLD发生及进展中的作用进行综述。

丁剑波, 李秀惠. 白细胞在非酒精性脂肪性肝病发生及进展中的作用[J]. 肝脏, 2024, 29(5): 599-602.

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参考文献

[1] Rinella M E, Neuschwander-Tetri B A, Siddiqui M S, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease[J]. Hepatology, 2023, 77(5): 1797-1835.
[2] Younossi Z M, Golabi P, Paik J M, et al. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review[J]. Hepatology, 2023, 77(4): 1335-1347.
[3] Le M H, Yeo Y H, Li X, et al. 2019 Global NAFLD Prevalence: a systematic review and meta-analysis[J]. Clin Gastroenterol Hepatol, 2022, 20(12): 2809-2817.
[4] 中华医学会肝病学分会脂肪肝和酒精性肝病学组, 中国医师协会脂肪性肝病专家委员会. 非酒精性脂肪性肝病防治指南(2018年更新版)[J]. 临床肝胆病杂志, 2018, 34(5): 947-957.
[5] Eslam M, Sanyal A J, George J. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease[J]. Gastroenterology, 2020, 158(7): 1999-2014.
[6] Eslam M, Newsome P N, Sarin S K, et al. A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement[J]. J Hepatol, 2020, 73(1): 202-209.
[7] Rinella M E, Lazarus J V, Ratziu V, et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature[J]. Hepatology, 2023.
[8] Wang S, Zhang C, Zhang G, et al. Association between white blood cell count and non-alcoholic fatty liver disease in urban Han Chinese: a prospective cohort study[J]. BMJ Open, 2016, 6(6): e10342.
[9] Chung G E, Yim J Y, Kim D, et al. Associations between white blood cell count and the development of incidental nonalcoholic fatty liver disease[J]. Gastroenterol Res Pract, 2016, 2016: 7653689.
[10] Wu L, Gao X, Guo Q, et al. The role of neutrophils in innate immunity-driven nonalcoholic steatohepatitis: lessons learned and future promise[J]. Hepatol Int, 2020, 14(5): 652-666.
[11] Shavakhi M, Nourigheimasi S, Dioso E, et al. Prognostic role of neutrophil to lymphocyte ratio in nonalcoholic fatty liver disease: a systematic review and meta-analysis[J]. Can J Gastroenterol Hepatol, 2022, 2022: 1554079.
[12] Peng Y, Li Y, He Y, et al. The role of neutrophil to lymphocyte ratio for the assessment of liver fibrosis and cirrhosis: a systematic review[J]. Expert Rev Gastroenterol Hepatol, 2018, 12(5): 503-513.
[13] Thibaut R, Gage M C, Pineda-Torra I, et al. Liver macrophages and inflammation in physiology and physiopathology of non-alcoholic fatty liver disease[J]. FEBS J, 2022, 289(11): 3024-3057.
[14] Kim H L, Chung G E, Park I Y, et al. Elevated peripheral blood monocyte fraction in nonalcoholic fatty liver disease[J]. Tohoku J Exp Med, 2011, 223(3): 227-233.
[15] Wang Y, Oeztuerk S, Kratzer W, et al. A nonclassical monocyte phenotype in peripheral blood is associated with nonalcoholic fatty liver disease: a report from an EMIL subcohort[J]. Horm Metab Res, 2016, 48(1): 54-61.
[16] Park J W, Jeong G, Kim S J, et al. Predictors reflecting the pathological severity of non-alcoholic fatty liver disease: comprehensive study of clinical and immunohistochemical findings in younger Asian patients[J]. J Gastroenterol Hepatol, 2007, 22(4): 491-497.
[17] Baeck C, Wehr A, Karlmark K R, et al. Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury[J]. Gut, 2012, 61(3): 416-426.
[18] Thibaut R, Gage M C, Pineda-Torra I, et al. Liver macrophages and inflammation in physiology and physiopathology of non-alcoholic fatty liver disease[J]. FEBS J, 2022, 289(11): 3024-3057.
[19] Reid D T, Reyes J L, Mcdonald B A, et al. Kupffer cells undergo fundamental changes during the development of experimental NASH and are critical in initiating liver damage and inflammation[J]. PLoS One, 2016, 11(7): e159524.
[20] Huang W, Metlakunta A, Dedousis N, et al. Depletion of liver Kupffer cells prevents the development of diet-induced hepatic steatosis and insulin resistance[J]. Diabetes, 2010, 59(2): 347-357.
[21] Krenkel O, Puengel T, Govaere O, et al. Therapeutic inhibition of inflammatory monocyte recruitment reduces steatohepatitis and liver fibrosis[J]. Hepatology, 2018, 67(4): 1270-1283.
[22] Baeck C, Wehr A, Karlmark K R, et al. Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury[J]. Gut, 2012, 61(3): 416-426.
[23] Barrow F, Khan S, Fredrickson G, et al. Microbiota-driven activation of intrahepatic B cells aggravates NASH through innate and adaptive signaling[J]. Hepatology, 2021, 74(2): 704-722.
[24] Winer D A, Winer S, Shen L, et al. B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies[J]. Nat Med, 2011, 17(5): 610-617.
[25] Wu Z, Xu J, Tan J, et al. Mesenteric adipose tissue B lymphocytes promote local and hepatic inflammation in non-alcoholic fatty liver disease mice[J]. J Cell Mol Med, 2019, 23(5): 3375-3385.
[26] Nishimura S, Manabe I, Takaki S, et al. Adipose natural regulatory B cells negatively control adipose tissue inflammation[J]. Cell Metab, 2013, 18(5): 759-766.
[27] Barrow F, Revelo X S. The B side of B cells in NAFLD[J]. Hepatology, 2022, 76(4): 914-916.
[28] Pfister D, Nunez N G, Pinyol R, et al. NASH limits anti-tumour surveillance in immunotherapy-treated HCC[J]. Nature, 2021, 592(7854): 450-456.
[29] O′Leary K. T cell drivers in NASH-HCC[J]. Nat Rev Cancer, 2021, 21(6): 341.
[30] Dudek M, Pfister D, Donakonda S, et al. Auto-aggressive CXCR6(+) CD8 T cells cause liver immune pathology in NASH[J]. Nature, 2021, 592(7854): 444-449.