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

Clinical implication of serum CK18 and FGF-21 levels in patients with non-alcoholic steatohepatitis

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。

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.