Increased serum mitochondrial creatine kinase activity as a risk for hepatocarcinogenesis in chronic hepatitis C patients
Increased serum mitochondrial creatine kinase activity as a risk for hepatocarcinogenesis in chronic hepatitis C patients
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DOI：
10.1002/ijc.28720
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发表时间：
2014-08-15
影响因子：
6.4
通讯作者：
Ikeda, Hitoshi
中科院分区：
文献类型：
--
作者：
Enooku, Kenichiro;Nakagawa, Hayato;Ikeda, Hitoshi
血清线粒体肌酸激酶（MtCK）活性增加，据报道，在肝硬化患者，虽然不突出，比肝细胞癌（HCC）患者。为探讨血清MtCK活性在慢性肝病中的临床意义，收集了171例慢性丙型肝炎患者。研究对象的血清MtCK活性与血清白蛋白、血小板计数、肝硬度值和血清天冬氨酸和丙氨酸转氨酶相关。在胆管结扎诱导的小鼠肝纤维化中，普遍存在的MtCK mRNA和蛋白表达显著增强，其免疫反应性增加，主要在肝细胞中。在平均2.7年的随访期间，21例患者发生了HCC，其中血清MtCK活性显著高于未发生HCC的患者。多因素考克斯回归分析显示，血清MtCK活性升高是HCC发生的危险因素。受试者工作特征分析确定MtCK预测HCC发展的临界值为9.0 U/L，受试者工作特征曲线下面积为0.754，敏感性为61.9%，特异性为92.8%，阴性预测值为94.2%。血清MtCK活性>9.0 U/L患者的HCC累积发病率显著高于血清MtCK活性> 15 kPa的患者。血清MtCK活性升高与肝纤维化程度及肝细胞损伤程度相关。血清MtCK活性升高是慢性丙型肝炎患者肝癌发生的独立风险。
Serum mitochondrial creatine kinase (MtCK) activity was reportedly increased in cirrhotic patients although less prominent than that in hepatocellular carcinoma (HCC) patients. To elucidate the clinical significance of serum MtCK activity in chronic liver disease, 171 chronic hepatitis C patients were enrolled. Serum MtCK activity in study subjects was correlated with serum albumin, platelet counts, liver stiffness values and serum aspartate and alanine aminotransferase. In mouse fibrotic liver induced by bile duct ligation, ubiquitous MtCK mRNA and protein expressions were significantly enhanced and its immunoreactivity was increased, predominantly in hepatocytes. During the mean follow-up period of 2.7 years, HCC developed in 21 patients, in whom serum MtCK activity was significantly higher than that in patients without HCC development. Multivariate Cox regression analysis revealed that higher serum MtCK activity was a risk for HCC development. A cutoff value of MtCK for the prediction of HCC development was determined as 9.0 U/L on receiver operating characteristics analysis, where area under receiver operating characteristics curve was 0.754, with a sensitivity of 61.9%, a specificity of 92.8% and a high negative predictive value of 94.2%. Cumulative incidence of HCC was significantly higher in patients with serum MtCK activity of >9.0 U/L compared to those with serum MtCK activity of 15 kPa. In conclusion, serum MtCK activity may be increased correlatively with the stage of liver fibrosis and hepatocellular damage. Increased serum MtCK activity is an independent risk for hepatocarcinogenesis in chronic hepatitis C patients.