肝硬化患者的血浆β-促胰岛紊水平
Plasma betatrophin levels in patients with liver cirrhosis.
作者信息
Arias-Loste Maria Teresa, García-Unzueta Maria Teresa, Llerena Susana, Iruzubieta Paula, Puente Angela, Cabezas Joaquín, Alonso Carmen, Cuadrado Antonio, Amado José Antonio, Crespo Javier, Fábrega Emilio
机构信息
Maria Teresa Arias-Loste, Susana Llerena, Paula Iruzubieta, Angela Puente, Joaquín Cabezas, Carmen Alonso, Antonio Cuadrado, Javier Crespo, Emilio Fábrega, Gastroenterology and Hepatology Unit, Marqués de Valdecilla University Hospital, Instituto de Investigación Sanitaria Valdecilla, Avenida Valdecilla s/n, 39008 Santander, Cantabria, Spain.
出版信息
World J Gastroenterol. 2015 Oct 7;21(37):10662-8. doi: 10.3748/wjg.v21.i37.10662.
AIM
To investigate the plasma levels of betatrophin in patients with cirrhosis.
METHODS
Forty patients diagnosed at the clinic with liver cirrhosis according to biological, ultrasonographic, or histological criteria were included. The severity of cirrhosis was classified according to Pugh's modification of Child's classification and MELD score. Insulin resistance (IR) was assessed by the Homeostasis Model Assessment. A total of 20 patients showed a MELD score higher than 14. The control group consisted in 15 sex-and aged-matched subjects. Fasting blood samples were obtained for subsequent analysis. Serum insulin was determined by Liaison automated immune chemiluminiscence assay (DiaSorin S.p.A.) using a sandwich assay. The sensitivity of the assay was 0.2 μU/mL. The intra and interassay variation coefficients were < 4% and < 10%, respectively. The normal values were between 2 and 17 μU/mL. Human active betatrophin was analyzed by specific quantitative sandwich ELISA (Aviscera Bioscience). The sensitivity of the assay was 0.4 ng/mL, and the intra and interassay reproducibility were < 6% and < 10%, respectively.
RESULTS
Plasma betatrophin levels were significantly increased in patients with cirrhosis compared with those in healthy subjects (P = 0.0001). Betatrophin levels were also associated with disease severity, being higher in Child-Pugh C patients compared to Child-Pugh B (P < 0.0005) and in patients who displayed a MELD score higher than 14 points compared to patients with lower punctuation (P = 0.01). In addition, we found a positive correlation between plasma betatrophin levels and the severity of cirrhosis according to Child-Pugh classification (r = 0.53; P < 0.01) or MELD score (r = 0.45; P < 0.01). In the overall cohort, a moderate correlation between serum betatrophin and plasmatic bilirrubin (r = 0.39; P < 0.01) has been observed, as well as an inverse correlation between betatrophin and albumin (r = -0.41; P < 0.01) or prothrombin time (r = -0.44; P <0.01). Moreover, insulin resistance was observed in 82.5% of the cirrhotic patients. In this group of patients, betatrophin levels were significantly higher than those in the group of patients without IR (P < 0.05).
CONCLUSION
Plasma betatrophin is increased in patients with cirrhosis. This increase is related to the severity of cirrhosis, as well as with the emergence of insulin resistance.
目的
研究肝硬化患者血浆中β-促细胞生成素水平。
方法
纳入40例根据生物学、超声或组织学标准在门诊诊断为肝硬化的患者。根据Child分级的Pugh改良法和终末期肝病模型（MELD）评分对肝硬化的严重程度进行分类。采用稳态模型评估法评估胰岛素抵抗（IR）。共有20例患者的MELD评分高于14分。对照组由15名年龄和性别匹配的受试者组成。采集空腹血样用于后续分析。采用Liaison自动免疫化学发光分析法（DiaSorin S.p.A.）通过夹心分析法测定血清胰岛素。该检测方法的灵敏度为0.2μU/mL。批内和批间变异系数分别<4%和<10%。正常值在2至17μU/mL之间。采用特异性定量夹心酶联免疫吸附测定法（Aviscera Bioscience）分析人活性β-促细胞生成素。该检测方法的灵敏度为0.4 ng/mL，批内和批间重复性分别<6%和<10%。
结果
与健康受试者相比，肝硬化患者的血浆β-促细胞生成素水平显著升高（P = 0.0001）。β-促细胞生成素水平也与疾病严重程度相关，Child-Pugh C级患者的β-促细胞生成素水平高于Child-Pugh B级患者（P < 0.0005），MELD评分高于14分的患者的β-促细胞生成素水平高于评分较低的患者（P = 0.01）。此外，我们发现根据Child-Pugh分类法（r = 0.53；P < 0.01）或MELD评分（r = 0.45；P < 0.01），血浆β-促细胞生成素水平与肝硬化严重程度呈正相关。在整个队列中，观察到血清β-促细胞生成素与血浆胆红素之间存在中度相关性（r = 0.39；P < 0.01），β-促细胞生成素与白蛋白（r = -0.41；P < 0.01）或凝血酶原时间（r = -0.44；P < 0.01）呈负相关。此外，82.5%的肝硬化患者存在胰岛素抵抗。在这组患者中，β-促细胞生成素水平显著高于无胰岛素抵抗的患者组（P < 0.05）。
结论
肝硬化患者血浆β-促细胞生成素升高。这种升高与肝硬化的严重程度以及胰岛素抵抗的出现有关。
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