首页> 中文期刊> 《中国全科医学》 >非酒精性脂肪性肝炎患儿血清肿瘤坏死因子α与细胞角质蛋白18的表达及意义研究

非酒精性脂肪性肝炎患儿血清肿瘤坏死因子α与细胞角质蛋白18的表达及意义研究

摘要

Objective To investigate the levels of serum TNF - α and CK - 18 of children with non - alcoholic steato-hepatitis(NASH)and to assess their correlation with histological examination. Methods 88 NAFLD children confirmed by liver biopsy and admitted to the Children′s Hospital of Zhengzhou from February 2010 to March 2013 were selected. According to NASH scoring criteria,the patients were divided into NASH group(64 cases)and non - NASH group(24 cases). The levels of TNF - α and CK - 18 were compared between the two groups and NASH children with different pathological features. ROC curve was drawn to analyze the accuracy of TNF - α and CK - 18 in diagnosing NASH. Results The levels of TNF - α and CK - 18 in NASH group were both higher than the non - NASH group〔(171 ± 24)μg/ L vs. (127 ± 19)μg/ L,(61 ± 9)μg/ L vs. (32 ± 8)μg/ L 〕(P < 0. 05). The steatosis,lobular inflammation,periportal inflammation and ballooning degeneration degrees ra-tio between the NASH group and non - NASH group all showed statistically significant differences(P < 0. 05). The NASH in-flammation score in NASH group was higher than the non - NASH group〔(7. 02 ± 0. 73)vs. (2. 91 ± 0. 80)〕(P < 0. 05). Spearman correlation analysis showed that the levels of TNF - α and CK - 18 were positively correlated with NASH inflammation score(rs = 0. 69,P < 0. 05;rs = 0. 73,P < 0. 05). Linear regression analysis showed that NASH inflammation score = 0. 05 × TNF - α - 2. 08,NASH inflammation score = 0. 1 × CK - 18 + 0. 58,and the difference was statistically significant( P =0. 000). The levels of TNF - α and CK - 18 in NASH children with steatosis,lobular inflammation,periportal inflammation and ballooning degeneration all showed statistically significant differences(P < 0. 05),and the levels of TNF - α and CK - 18 in-creased as the above mentioned diseases aggravated. The pairwise comoparison also showed statistically significant difference(P <0. 05). Spearman correlation analysis showed that the levels of TNF - α and CK - 18 were positively correlated with steatosis, lobular inflammation,periportal inflammation and ballooning degeneration degrees ratio(P < 0. 05). Area under the ROC curve of TNF - α and CK - 18 was 0. 83 and 0. 92 respectively. The best sensitivity and specificity was 0. 79 and 0. 75 when the cut - off point of TNF - α was 136 μg/ L. While the best sensitivity and specificity was 0. 82 and 0. 85 when the cut - off point of CK - 18 was 42 μg/ L. Conclusion TNF - α and CK - 18 can be used as a better non - invasive biomarkers for NASH diagnosis.%目的:探讨非酒精性脂肪性肝炎(NASH)患儿血清肿瘤坏死因子α(TNF -α)与细胞角质蛋白18(CK -18)水平及其与组织学检查结果的相关性。方法选取2010年2月-2013年3月在郑州市儿童医院内科住院、肝组织活检证实为非酒精性脂肪肝病的患儿88例,根据 NASH 炎症评分将其分为 NASH 组64例和非 NASH 组24例。比较两组血清TNF -α、CK -18水平及不同病理特征 NASH 组患儿 TNF -α、CK -18水平。绘制受试者工作特征(ROC)曲线分析 TNF -α、CK -18诊断 NASH 的准确度。结果 NASH 组 TNF -α〔(171±24)μg/ L 与(127±19)μg/ L〕、CK -18〔(61±9)μg/ L 与(32±8)μg/ L〕水平均高于非 NASH 组(P <0.05)。NASH 组与非 NASH 组患儿不同程度脂肪变、小叶炎症、汇管区炎症、气球样变发生率比较,差异均有统计学意义( P <0.05)。NASH 组 NASH炎症评分高于非 NASH 组〔(7.02±0.73)分与(2.91±0.80)分,P <0.05〕。Spearman 相关分析显示,血清TNF -α、CK -18水平与 NASH 炎症评分均呈正相关(rs =0.69,P <0.05;rs =0.73,P <0.05)。直线回归分析结果显示,NASH 炎症评分=0.05× TNF -α-2.08,NASH 炎症评分=0.1× CK -18+0.58,差异均有统计学意义( P =0.000)。不同程度脂肪变、小叶炎症、汇管区炎症、气球样变 NASH 组患儿 TNF -α、CK -18水平比较,差异均有统计学意义(P <0.05);NASH 组患儿随着脂肪变、小叶炎症、汇管区炎症、气球样变程度的加重 TNF -α、CK -18水平逐渐升高,组间两两比较差异均有统计学意义(P <0.05)。Spearman 相关分析结果显示,NASH 组患儿脂肪变、小叶炎症、汇管区炎症、气球样变程度与 TNF -α、CK -18水平均呈正相关(P <0.05)。TNF -α诊断 NASH 的 ROC 曲线下面积为0.83,CK -18诊断 NASH 的 ROC 曲线下面积为0.92。取 TNF -α截点值为136μg/ L 时,可获得最佳灵敏度0.79和特异度0.75。取CK -18截点值为42μg/ L,可获得最佳灵敏度0.82和特异度0.85。结论 TNF -α和CK -18可以作为一种能较好地诊断儿童 NASH 的非侵入性生物标志物。

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