三种炎性因子在慢性乙型肝炎合并非酒精性脂肪性肝病患者血清中的表达及作用

Expressions and roles of three inflammatory cytokines in chronic hepatitis B patients with nonalcoholic fatty liver disease

目的探讨细胞角蛋白（CK18）片段M30和M65、胸腺素β4（Tβ4）及TNF-α在CHB合并脂肪肝患者的脂肪变及炎症、纤维化发展过程中的作用。方法选择CHB合并非酒精性脂肪性肝病（NAFLD）患者46例，单纯CHB患者42例。采用ELISA法检测两组患者血清CK-18 M30、CK-18 M65、Tβ4及TNF-α水平。同时分析CHB合并NAFLD患者血清炎性因子与生物化学指标和病理指标的相关性。统计学处理采用t检验和χ2检验，相关性分析采用Pearson和Logistic回归分析。结果CHB合并NAFLD患者血清CK-18 M30的水平为（614.48±471.43） U/L，明显高于单纯CHB患者的（374.50±231.04） U/L，差异有统计学意义（t＝2.988，P〈0.01）。CHB合并NAFLD患者血清CK18 M65、Tβ4和TNF-α水平分别为（369.41±262.21） U/L、（0.80±0.32） mg/L和（54.87±20.36） ng/L，单纯CHB患者分别为（296.50±231.44） U/L、（0.68±0.30） mg/L和（51.88±20.60） ng/L，差异均无统计学意义（t值分别为1.378、1.810、0.685，均P〉0.05）。CHB合并NAFLD患者血清CK-18 M30水平与ALT、三酰甘油、空腹血糖、肝组织炎症活动度分级（G）、纤维化分期（S）及脂肪变分级（F）呈正相关（r值分别为0.507、0.456、0.384、0.551、0.458、0.457，均P〈0.01），Tβ4水平与肝组织炎症活动度和纤维化分期呈负相关（r值分别为－0.371、－0.308，均P〈0.05），TNF-α水平与肝组织炎症活动度及脂肪变分级呈正相关（r值分别为0.570、0.441，均P〈0.01）。Logistic回归提示，CK-18 M30、Tβ4和TNF-α分别是CHB合并NAFLD、显著炎症纤维化及中重度脂肪变的独立预测因子。结论CK-18 M30、Tβ4和TNF-α与CHB合并NAFLD患者肝组织脂肪变的发生、炎症纤维化进展相关。

ObjectiveTo investigate the roles of cytokeratin 18 （CK18） M30 and M65, thymosin beta 4 （Tβ4） and tumor necrosis factor （TNF）-α in hepatic steatosis and development of inflammatory and fibrosis in chronic hepatitis B （CHB） patients with nonalcoholic fatty liver disease （NAFLD）. MethodsA total of 46 CHB patients with NAFLD and 42 CHB patients were collected. Serum CK-18 M30, M65, Tβ4 and TNF-α levels were measured by enzyme linked immunosorbent assay （ELISA） in two groups. The associations between inflammatory factors levels and biochemical or pathological indicators were analyzed. The statistical analysis was conducted by t test and chi square test of two independent samples. The correlation analysis was performed by Pearson and Logistic regression analysis.ResultsThe mean serum CK-18 M30 level in CHB with NAFLD group was （614.48±471.43） U/L, which was significantly higher than that in CHB group （374.50±231.04） U/L （t=2.988, P〈0.01）. The mean levels of CK18 M65, Tβ4 and TNF-α in CHB with NAFLD group were （369.41±262.21） U/L, （0.80±0.32） mg/L and （54.87±20.36） ng/L, respectively, and those in CHB group were （296.50±231.44） U/L, （0.68±0.30） mg/L and （51.88±20.60） ng/L, respectively. There were no difference between CHB with NAFLD group and CHB group （t=1.378, 1.810 and 0.685, respectively, all P〉0.05）. In CHB with NAFLD patients, the CK-18 M30 level was positively correlated with alanine aminotransferase, triglyceride, fasting blood glucose, histology inflammation score, fibrosis score and steatosis （r=0.507, 0.456, 0.384, 0.551, 0.458 and 0.457, respectively, all P〈0.01）. Tβ4 level was negatively correlated with inflammation and fibrosis score （r=-0.371 and -0.308, respectively, P〈0.05）. TNF-α level was positively correlated with inflammation score and steatosis （r=0.570 and 0.441, respectively, P〈0.01）. CK-18 M30, Tβ4 and TNF-α were independent predictors of CHB combined with NAFLD, progressive inflammatory fibrosis and severe steatosis.ConclusionsSerum CK-18 M30, Tβ4 and TNF-α levels are associated with hepatic steatosis, development of inflammation and fibrosis in CHB with NAFLD patients.