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血清细胞角蛋白-18与非酒精性脂肪性肝病进展或消退的相关性

Correlation between serum cytokeratin-18 and the progression or regression of non-alcoholic fatty liver disease.

作者信息

Kawanaka Miwa, Nishino Ken, Nakamura Jun, Urata Noriyo, Oka Takahito, Goto Daisuke, Suehiro Mitsuhiko, Kawamoto Hirofumi, Yamada Gotaro

机构信息

Department of Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.

出版信息

Ann Hepatol. 2015 Nov-Dec;14(6):837-44. doi: 10.5604/16652681.1171767.

Abstract

BACKGROUND

Diagnosis of non-alcoholic fatty liver disease (NAFLD) is limited by the need for liver biopsies. Serum cytokeratin 18 (CK-18) levels have been investigated as potential biomarkers for the presence of NAFLD and non-alcoholic steatohepatitis (NASH). Herein, we assessed the correlation between CK-18 levels and NAFLD progression.

MATERIAL AND METHODS

Serum CK-18 levels were estimated using the M30 antibody enzyme-linked immunosorbent assay in 147 patients diagnosed with NAFLD. In 72 patients, disease progression was evaluated by repeated liver biopsy, which was conducted after 4.3 ± 2.6 years. The relationship between the CK-18 levels and liver histological findings was assessed.

RESULTS

The CK-18 levels were useful for identifying NAFLD patients with NAFLD activity scores (NAS) ≥ 5 (NAS ≥ 5 vs. ≤ 4: 675.1 U/L vs. 348.7 U/L; p < 0.0001). A cut-off value of 375 U/L was calculated using the receiver operating characteristic curve approach, with a specificity and sensitivity of 81.5 and 65%, respectively, for the diagnosis of NASH. Among the 72 patients who underwent repeated liver biopsy, 11 patients with a progressed NAS also had significantly increased serum CK-18 levels (p < 0.01); in 30 patients with an improved NAS, there was a significant improvement in the mean CK-18 levels (p < 0.0001). The 31 patients with static NAS had static CK-18 levels.

CONCLUSIONS

In conclusion, serum CK-18 levels can predict NAS ≥ 5 in NAFLD patients. In NAFLD patients, serum CK-18 levels reflect NAS values and correlate with histological changes, and they appear to be useful indicators of progression and improvement.

摘要

背景

非酒精性脂肪性肝病(NAFLD)的诊断因需要进行肝脏活检而受到限制。血清细胞角蛋白18(CK-18)水平已被作为NAFLD和非酒精性脂肪性肝炎(NASH)存在的潜在生物标志物进行研究。在此,我们评估了CK-18水平与NAFLD进展之间的相关性。

材料与方法

采用M30抗体酶联免疫吸附试验对147例诊断为NAFLD的患者的血清CK-18水平进行评估。在72例患者中,通过重复肝脏活检评估疾病进展,重复活检在4.3±2.6年后进行。评估CK-18水平与肝脏组织学结果之间的关系。

结果

CK-18水平有助于识别NAFLD活动评分(NAS)≥5的NAFLD患者(NAS≥5 vs.≤4:675.1 U/L vs.348.7 U/L;p<0.0001)。使用受试者工作特征曲线法计算得出截断值为375 U/L,对NASH诊断的特异性和敏感性分别为81.5%和65%。在72例接受重复肝脏活检的患者中,11例NAS进展的患者血清CK-18水平也显著升高(p<0.01);在30例NAS改善的患者中,平均CK-18水平有显著改善(p<0.0001)。31例NAS稳定的患者CK-18水平稳定。

结论

总之,血清CK-18水平可预测NAFLD患者的NAS≥5。在NAFLD患者中,血清CK-18水平反映NAS值并与组织学变化相关,似乎是疾病进展和改善的有用指标。

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