非酒精性脂肪性肝炎患者血清CK18和FGF-21水平变化及其临床意义探讨

doi:10.3969/j.issn.1672-5069.2021.06.017

摘要/Abstract

摘要： 目的探讨非酒精性脂肪性肝炎(NASH)患者血清细胞角蛋白18片段M30(CK18-M30)和成纤维细胞生长因子-21(FGF-21)水平变化及其临床意义。方法 2018年10月～2020年10月我院收治的85例NASH患者和45例同期体检的健康人,NASH患者接受肝活检。采用ELISA法检测血清CK18-M30和FGF-21水平,使用全自动生化分析仪检测空腹血糖(FPG)、胰岛素(FIN)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和三酰甘油(TG),用稳态模型评价胰岛素抵抗指数(HOMA-IR)。结果 NASH患者血清FIN、FPG、TC、TG、HOMA-IR、LDL-C、CK18-M30和FGF-21水平分别为(17.1±4.9)mIU/L、(5.4±1.4)mmol/L、(5.4±0.9)mmol/L、(2.0±0.6)mmol/L、(1.4±0.2)、(3.6±0.6)mmol/L、(96.4±14.6)U/L和(283.6±79.2)pg/mL,均显著高于健康人【分别为(13.1±1.1)mIU/L、(4.9±0.9)mmol/L、(4.8±0.7)mmol/L、(1.5±0.2)mmol/L、(1.3±0.1)、(2.6±0.5)mmol/L、(70.3±8.7)U/L和(155.3±60.4)pg/mL,均P＜0.05】;48例中重度NASH患者血清FIN、FPG、TC、TG、CK18-M30和FGF-21水平分别为(18.4±43.9)mIU/L、(5.7±1.3)mmol/L、(5.6±0.9)mmol/L、(2.1±0.5)mmol/L、(101.9±13.9)U/L和(299.5±77.4)pg/mL,均显著高于37例轻度NASH患者【分别为(15.3±4.2)mIU/L、(5.1±1.2)mmol/L、(4.9±0.8)mmol/L、(1.8±0.6)mmol/L、(89.3±12.5)U/L和(263.0±69.8)pg/mL,均P＜0.05】;35例有合并症(高血脂、糖尿病、高血压)的NASH患者血清TC、TG、HOMA-IR、CK18-M30和FGF-21水平分别为(5.8±0.9)mmol/L、(2.2±0.5)mmol/L、(1.5±0.6)、(101.7±14.3)U/L和(306.9±63.1)pg/mL,均显著高于无合并症患者【分别为(5.1±0.8)mmol/L、(1.9±0.6)mmol/L、(1.3±0.5)、(92.6±13.1)U/L和(267.2±77.9)pg/mL,均P＜0.05】。结论 NASH患者血清CK18-M30和FGF-21水平显著升高,在中重度肝脂肪变及有合并高血脂、高血压和糖尿病的NASH患者,这些指标的升高更显著,检测血清CK18-M30和FGF-21水平,可能有助于评估NASH病情。

关键词: 非酒精性脂肪性肝炎, 细胞角蛋白18, 成纤维细胞生长因子-21, 胰岛素抵抗

Abstract: Objective The aim of this study was to explore the clinical implication of serum cytokeratin 18 fragment M30 (CK18-M30) and fibroblast growth factor-21 (FGF-21) levels in patients with non-alcoholic steatohepatitis (NASH). Methods 85 patients with NASH and 5 healthy individuals were recruited in our hospital between October 2018 and October 2020, and liver biopsies were performed in patients with NASH. Serum CK18-M30 and FGF-21 levels were detected by ELISA. The blood glucose-lipid metabolism indexes, such as fasting blood glucose (FPG), insulin (FIN), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triacylglycerol (TG)], and homeostasis model assessment of insulin resistance (HOMA-IR) were detected by full-automatic biochemical analyzer. Results Serum FIN, FPG, TC, TG, HOMA-IR, LDL-C, CK18-M30 and FGF-21 levels in patients were (17.1±4.9)mIU/L,(5.4±1.4)mmol/L, (5.4±0.9)mmol/L, (2.0±0.6)mmol/L, (1.4±0.2), (3.6±0.6)mmol/L, (96.4±14.6)U/L and (283.6±79.2)pg/mL, all significantly higher than [(13.1±1.1)mIU/L, (4.9±0.9)mmol/L, (4.8±0.7)mmol/L, (1.5±0.2)mmol/L, (1.3±0.1), (2.6±0.5)mmol/L, (70.3±8.7)U/L and (155.3±60.4)pg/mL, respectively, P＜0.05]; serum FIN, FPG, TC, TG, CK18-M30 and FGF-21 levels in 48 patients with moderate to severe NASH were (18.4±43.9)mIU/L, (5.7±1.3)mmol/L, (5.6±0.9)mmol/L, (2.1±0.5)mmol/L, (101.9±13.9)U/L and (299.5±77.4)pg/mL, all significantly higher than [(15.3±4.2)mIU/L, (5.1±1.2)mmol/L, (4.9±0.8)mmol/L, (1.8±0.6)mmol/L, (89.3±12.5)U/L and (263.0±69.8)pg/mL, respectively, P＜0.05] in 37 patients with mild NASH; serum TC, TG, HOMA-IR, CK18-M30 and FGF-21 levels in 35 NASH patients with concomitant diseases such as hyperlipidemia, diabetes and high blood pressure, were (5.8±0.9)mmol/L, (2.2±0.5)mmol/L, (1.5±0.6), (101.7±14.3)U/L and (306.9±63.1)pg/mL, all significantly higher than [(5.1±0.8)mmol/L, (1.9±0.6)mmol/L, (1.3±0.5), (92.6±13.1)U/L and (267.2±77.9)pg/mL, respectively, all P＜0.05] in those without. Conclusion Serum CK18-M30 and FGF-21 levels increase in patients with NASH, which is correlated to the disease severity and concomitant hyperlipidemia, higher blood pressure and diabetes. The detection of serum CK18-M30 and FGF-21 levels might be helpful in assessing the diagnosis and management.

Key words: Non-alcoholic steatohepatitis, Cytokeratin 18, Fibroblast growth factor-21, Insulin resistance

闻啟富, 马利军, 王晓亮. 非酒精性脂肪性肝炎患者血清CK18和FGF-21水平变化及其临床意义探讨[J]. 实用肝脏病杂志, 2021, 24(6): 835-838.

Wen Qifu, Ma Lijun, Wang Xiaoliang. Clinical implication of serum CK18 and FGF-21 levels in patients with non-alcoholic steatohepatitis[J]. Journal of Practical Hepatology, 2021, 24(6): 835-838.

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