Arab Juan Pablo, Hernández-Rocha Cristián, Morales Carolina, Vargas José Ignacio, Solís Nancy, Pizarro Margarita, Robles Camila, Sandoval Daniela, Ponthus Simon, Benítez Carlos, Barrera Francisco, Soza Alejandro, Riquelme Arnoldo, Arrese Marco
Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Gastroenterol Hepatol. 2017 Jun-Jul;40(6):388-394. doi: 10.1016/j.gastrohep.2017.02.009. Epub 2017 Mar 28.
Nonalcoholic steatohepatitis (NASH) is the most aggressive form of nonalcoholic fatty liver disease (NAFLD) and involves the risk of progression to more advanced stages of liver disease. Non-invasive methods are needed to identify patients with NASH.
To evaluate the diagnostic performance of the determination of serum levels of cytokeratin-18 (CK-18) as a non-invasive marker of NASH in the Chilean population.
Serum CK-18 levels were determined in a group of 41 patients with biopsy-proven NAFLD. NASH diagnosis was based on Brunt's criteria (histological parameters and ballooning), and the NAFLD activity score (NAS) and the presence of fibrosis were determined. The correlation between the NAFLD activity score (NAS) and CK-18 was evaluated with Spearman's rank correlation coefficient. A ROC curve was produced to assess the diagnostic value of CK-18 for NASH. The NAFLD fibrosis score (NFS) (to predict fibrosis and NASH) was compared to CK-18 with simple linear regression. Data were expressed in median [25th-75th percentile] and evaluated with the Wilcoxon rank test.
The mean age of the study group (23% male) was 50.4±11.1 years. 34.2% were diagnosed with NASH (NAS≥5). CK-18 levels were significantly higher in patients with NASH versus those without NASH (183.6 IU/l [97.4 to 734.4] vs. 117.2 IU/l [83.8 to 954.8], p= 0.016). CK-18 levels were a good predictor of NASH on biopsy with an area under the curve (AUC) of 0.732 (95% CI, 0.572 to 0.897). A CK-18 cut-off of 130.5 IU/l had a sensitivity of 92.9%, specificity of 63%, positive predictive value of 56.5% and negative predictive value of 94.4%, and was able to correctly classify 73.2% of patients with NASH. NFS identified advanced liver fibrosis (AUC 0.739, 95% CI, 0.56-0.91), but was of limited value to identify NASH (AUC 0.413, 95% CI, 0.21-0.61).
CK-18 is a good non-invasive marker for NASH. Although NFS was found to be an accurate marker of advanced liver fibrosis, it was not of value to identify NASH. In patients with NAFLD, CK-18 and NFS could be useful in predicting NASH and liver fibrosis, respectively.
非酒精性脂肪性肝炎（NASH）是最严重的非酒精性脂肪性肝病（NAFLD）形式，存在进展至更晚期肝病的风险。需要采用非侵入性方法来识别NASH患者。
评估测定血清细胞角蛋白-18（CK-18）水平作为智利人群中NASH的非侵入性标志物的诊断性能。
对一组41例经活检证实为NAFLD的患者测定血清CK-18水平。NASH诊断基于布伦特标准（组织学参数和气球样变），并确定NAFLD活动评分（NAS）和纤维化情况。用Spearman等级相关系数评估NAFLD活动评分（NAS）与CK-18之间的相关性。绘制ROC曲线以评估CK-18对NASH的诊断价值。用简单线性回归将NAFLD纤维化评分（NFS）（用于预测纤维化和NASH）与CK-18进行比较。数据以中位数[第25-75百分位数]表示，并用Wilcoxon秩和检验进行评估。
研究组的平均年龄为50.4±11.1岁（男性占23%）。34.2%被诊断为NASH（NAS≥5）。与无NASH的患者相比，NASH患者的CK-18水平显著更高（183.6 IU/l[97.4至734.4]对117.2 IU/l[83.8至954.8]，p = 0.016）。CK-18水平是活检时NASH的良好预测指标，曲线下面积（AUC）为0.732（95%CI，0.572至0.897）。CK-18临界值为130.5 IU/l时，敏感性为92.9%，特异性为63%，阳性预测值为56.5%，阴性预测值为94.4%，能够正确分类73.2%的NASH患者。NFS可识别晚期肝纤维化（AUC 0.739，95%CI，0.56 - 0.91），但对识别NASH价值有限（AUC 0.413，95%CI，0.21 - 0.61）。
CK-18是NASH的良好非侵入性标志物。虽然发现NFS是晚期肝纤维化的准确标志物，但对识别NASH无价值。在NAFLD患者中，CK-18和NFS分别可用于预测NASH和肝纤维化。
