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血浆 ADAMTS13 预测慢性乙型和丙型肝炎肝细胞癌的发生。

Prediction of hepatocellular carcinoma development by plasma ADAMTS13 in chronic hepatitis B and C.

机构信息

Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.

出版信息

Cancer Epidemiol Biomarkers Prev. 2011 Oct;20(10):2204-11. doi: 10.1158/1055-9965.EPI-11-0464. Epub 2011 Aug 29.

Abstract

BACKGROUND

Chronic liver injury evokes a wound healing response, promoting fibrosis and finally hepatocellular carcinoma (HCC), in which hepatic stellate cells play an important role. Although a blood marker of hepatic stellate cells is not known, those cells importantly contribute to the regulation of plasma a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) activity, a defect of which causes thrombotic thrombocytopenic purpura.

METHODS

Plasma ADAMTS13 was evaluated in chronic hepatitis B or C patients with or without HCC.

RESULTS

Plasma ADAMTS13 activity significantly correlated with serum aspartate aminotransferase and alanine aminotransferase, liver stiffness value, and aspartate aminotransferase-to-platelet ratio index, irrespective of the presence of HCC, suggesting that it may reflect hepatocellular damage and subsequent wound healing and fibrosis as a result of hepatic stellate cell action. During the three-year follow-up period for patients without HCC, it developed in 10 among 81 patients. Plasma ADAMTS13 activity was significantly higher in patients with HCC development than in those without and was a significant risk for HCC development by univariate and multivariate analyses. Furthermore, during the one-year follow-up period for patients with HCC treated with radiofrequency ablation, HCC recurred in 55 among 107 patients. Plasma ADAMTS13 activity or antigen level was significantly higher in patients with HCC recurrence than in those without and was retained as a significant risk for HCC recurrence by multivariate analysis.

CONCLUSIONS

Higher plasma ADAMTS13 activity and antigen level was a risk of HCC development in chronic liver disease.

IMPACT

Plasma ADAMTS13 as a potential marker of hepatic stellate cells may be useful in the prediction of hepatocarcinogenesis.

摘要

背景

慢性肝损伤会引发创伤愈合反应,促进纤维化,最终导致肝细胞癌(HCC),其中肝星状细胞起着重要作用。虽然肝星状细胞的血液标志物尚不清楚,但这些细胞对调节血浆 a 型血小板反应蛋白 13 金属蛋白酶(ADAMTS13)的活性非常重要,其缺陷会导致血栓性血小板减少性紫癜。

方法

评估慢性乙型或丙型肝炎患者是否伴有 HCC 时的血浆 ADAMTS13。

结果

血浆 ADAMTS13 活性与血清天冬氨酸转氨酶和丙氨酸转氨酶、肝硬度值和天冬氨酸转氨酶与血小板比值指数显著相关,无论是否存在 HCC,这表明它可能反映肝细胞损伤以及随后的肝星状细胞作用引起的创伤愈合和纤维化。在无 HCC 的患者三年随访期间,其中 81 例中有 10 例发展为 HCC。与无 HCC 发展的患者相比,有 HCC 发展的患者的血浆 ADAMTS13 活性显著更高,并且在单因素和多因素分析中是 HCC 发展的显著危险因素。此外,在接受射频消融治疗的 HCC 患者的一年随访期间,其中 107 例中有 55 例 HCC 复发。与无 HCC 复发的患者相比,有 HCC 复发的患者的血浆 ADAMTS13 活性或抗原水平显著更高,并且在多因素分析中保留了 HCC 复发的显著危险因素。

结论

较高的血浆 ADAMTS13 活性和抗原水平是慢性肝病中 HCC 发展的危险因素。

意义

血浆 ADAMTS13 作为肝星状细胞的潜在标志物,可能有助于预测肝癌发生。

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