CAJ | 학술논문

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。目的：探討非酒精性脂肪性肝炎（NASH）患兒血清腫瘤壞死因子α（TNF -α）與細胞角質蛋白18（CK -18）水平及其與組織學檢查結果的相關性。方法選取2010年2月-2013年3月在鄭州市兒童醫院內科住院、肝組織活檢證實為非酒精性脂肪肝病的患兒88例，根據 NASH 炎癥評分將其分為 NASH 組64例和非 NASH 組24例。比較兩組血清TNF -α、CK -18水平及不同病理特徵 NASH 組患兒 TNF -α、CK -18水平。繪製受試者工作特徵（ROC）麯線分析 TNF -α、CK -18診斷 NASH 的準確度。結果 NASH 組 TNF -α〔（171±24）μg/ L 與（127±19）μg/ L〕、CK -18〔（61±9）μg/ L 與（32±8）μg/ L〕水平均高于非 NASH 組（P <0.05）。NASH 組與非 NASH 組患兒不同程度脂肪變、小葉炎癥、彙管區炎癥、氣毬樣變髮生率比較，差異均有統計學意義（ P <0.05）。NASH 組 NASH炎癥評分高于非 NASH 組〔（7.02±0.73）分與（2.91±0.80）分，P <0.05〕。Spearman 相關分析顯示，血清TNF -α、CK -18水平與 NASH 炎癥評分均呈正相關（rs =0.69，P <0.05；rs =0.73，P <0.05）。直線迴歸分析結果顯示，NASH 炎癥評分=0.05× TNF -α-2.08，NASH 炎癥評分=0.1× CK -18＋0.58，差異均有統計學意義（ P =0.000）。不同程度脂肪變、小葉炎癥、彙管區炎癥、氣毬樣變 NASH 組患兒 TNF -α、CK -18水平比較，差異均有統計學意義（P <0.05）；NASH 組患兒隨著脂肪變、小葉炎癥、彙管區炎癥、氣毬樣變程度的加重 TNF -α、CK -18水平逐漸升高，組間兩兩比較差異均有統計學意義（P <0.05）。Spearman 相關分析結果顯示，NASH 組患兒脂肪變、小葉炎癥、彙管區炎癥、氣毬樣變程度與 TNF -α、CK -18水平均呈正相關（P <0.05）。TNF -α診斷 NASH 的 ROC 麯線下麵積為0.83，CK -18診斷 NASH 的 ROC 麯線下麵積為0.92。取 TNF -α截點值為136μg/ L 時，可穫得最佳靈敏度0.79和特異度0.75。取CK -18截點值為42μg/ L，可穫得最佳靈敏度0.82和特異度0.85。結論 TNF -α和CK -18可以作為一種能較好地診斷兒童 NASH 的非侵入性生物標誌物。
목적：탐토비주정성지방성간염（NASH）환인혈청종류배사인자α（TNF -α）여세포각질단백18（CK -18）수평급기여조직학검사결과적상관성。방법선취2010년2월-2013년3월재정주시인동의원내과주원、간조직활검증실위비주정성지방간병적환인88례，근거 NASH 염증평분장기분위 NASH 조64례화비 NASH 조24례。비교량조혈청TNF -α、CK -18수평급불동병리특정 NASH 조환인 TNF -α、CK -18수평。회제수시자공작특정（ROC）곡선분석 TNF -α、CK -18진단 NASH 적준학도。결과 NASH 조 TNF -α〔（171±24）μg/ L 여（127±19）μg/ L〕、CK -18〔（61±9）μg/ L 여（32±8）μg/ L〕수평균고우비 NASH 조（P <0.05）。NASH 조여비 NASH 조환인불동정도지방변、소협염증、회관구염증、기구양변발생솔비교，차이균유통계학의의（ P <0.05）。NASH 조 NASH염증평분고우비 NASH 조〔（7.02±0.73）분여（2.91±0.80）분，P <0.05〕。Spearman 상관분석현시，혈청TNF -α、CK -18수평여 NASH 염증평분균정정상관（rs =0.69，P <0.05；rs =0.73，P <0.05）。직선회귀분석결과현시，NASH 염증평분=0.05× TNF -α-2.08，NASH 염증평분=0.1× CK -18＋0.58，차이균유통계학의의（ P =0.000）。불동정도지방변、소협염증、회관구염증、기구양변 NASH 조환인 TNF -α、CK -18수평비교，차이균유통계학의의（P <0.05）；NASH 조환인수착지방변、소협염증、회관구염증、기구양변정도적가중 TNF -α、CK -18수평축점승고，조간량량비교차이균유통계학의의（P <0.05）。Spearman 상관분석결과현시，NASH 조환인지방변、소협염증、회관구염증、기구양변정도여 TNF -α、CK -18수평균정정상관（P <0.05）。TNF -α진단 NASH 적 ROC 곡선하면적위0.83，CK -18진단 NASH 적 ROC 곡선하면적위0.92。취 TNF -α절점치위136μg/ L 시，가획득최가령민도0.79화특이도0.75。취CK -18절점치위42μg/ L，가획득최가령민도0.82화특이도0.85。결론 TNF -α화CK -18가이작위일충능교호지진단인동 NASH 적비침입성생물표지물。
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.