丙氨酸氨基转移酶水平是非酒精性脂肪性肝病肝细胞凋亡的替代生物标志物吗?
Is alanine aminotransferase level a surrogate biomarker of hepatic apoptosis in nonalcoholic fatty liver disease?
机构信息
Cerrahpasa Medical Faculty of Istanbul University, Department of Gastroenterology, Fatih, 34303 Istanbul, Turkey.
出版信息
Biomark Med. 2010 Apr;4(2):205-14. doi: 10.2217/bmm.09.88.
AIM
To evaluate the serum alanine aminotransferase (ALT) variabilities in nonalcoholic fatty liver disease (NAFLD) and correlate it with hepatocyte apoptosis and oxidative stress parameters.
METHODS
24 patients with NAFLD and normal ALT were compared with 26 subjects with NAFLD and elevated ALT. Liver oxidative stress was estimated on the basis of malondialdehyde, superoxide dismutase and glutathione. Immunohistochemistry was performed for activated caspase 3 and 8, nuclear factor-kappaB, antiapoptotic Bcl-2 protein and serum TNF receptor levels were measured.
RESULTS
The mean caspase 3 and 8 activity scores, oxidative stress parameters, necroinflammatory grade and prevalence of severe fibrosis were comparable across the groups with normal versus elevated ALT. Patients with nonalcoholic steatohepatitis had significantly higher caspase 3 and 8 activity (percentage of cells with positive staining per high power field), and serum malondialdehyde (mmol/l) levels than those with simple steatosis. ALT elevation was not a risk factor for advanced necroinflammatory grade and fibrosis. A receiver operating characteristic curve did not demonstrate sensitivity and specificity for discriminative power of ALT.
CONCLUSION
Apoptosis and oxidative stress are the main processes contributing to disease progression in NAFLD. ALT values do not correlate with the parameters of apoptosis and oxidative stress. The disease severity can only be determined by liver biopsy.
目的
评估非酒精性脂肪性肝病(NAFLD)患者血清丙氨酸氨基转移酶(ALT)的变异性,并将其与肝细胞凋亡和氧化应激参数相关联。
方法
将 24 例 ALT 正常的 NAFLD 患者与 26 例 ALT 升高的 NAFLD 患者进行比较。根据丙二醛、超氧化物歧化酶和谷胱甘肽来评估肝氧化应激。采用免疫组化法检测激活的 caspase-3 和 caspase-8、核因子-κB、抗凋亡 Bcl-2 蛋白和血清 TNF 受体水平。
结果
正常 ALT 组与升高 ALT 组之间,caspase-3 和 caspase-8 活性评分、氧化应激参数、坏死性炎症分级和严重纤维化的患病率均无显著差异。非酒精性脂肪性肝炎患者的 caspase-3 和 caspase-8 活性(高倍视野阳性细胞百分比)以及血清丙二醛(mmol/L)水平显著高于单纯性脂肪变性患者。ALT 升高不是进展性严重坏死性炎症和纤维化的危险因素。ROC 曲线未显示 ALT 对鉴别力的敏感性和特异性。
结论
凋亡和氧化应激是 NAFLD 疾病进展的主要过程。ALT 值与凋亡和氧化应激参数不相关。疾病严重程度只能通过肝活检来确定。