Darweesh Samar K, AbdElAziz Rasha A, Abd-ElFatah Dina S, AbdElazim Naglaa A, Fathi Shaimaa A, Attia Dina, AbdAllah Mohammed
Departments of Hepatology and Endemic Medicine.
Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University.
Eur J Gastroenterol Hepatol. 2019 May;31(5):633-641. doi: 10.1097/MEG.0000000000001385.
Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common cause of chronic liver disease worldwide. Multiple diagnostic noninvasive methods for NAFLD were studied (both serological and imaging), either single or combined. Attention has been focused on cytokeratin-18 (CK18) as a novel serological marker for the diagnosis of steatosis/fibrosis in NAFLD and hepatitis C virus (HCV) patients.
The aim of this study was to evaluate serum CK18 in NAFLD and HCV fibrosis/steatosis and also to correlate its performance with the diagnostic accuracy of transient elastography (TE) and controlled attenuation parameter (CAP) in the diagnosis of fibrosis/steatosis in these patients.
Three equal groups of participants were enrolled (n=135): group I included patients with chronic HCV, group II included NAFLD patients, and group III included control participants. For all groups, TE/CAP and labs including serum CK18 were performed. Liver biopsy was performed for the NAFLD group.
Serum CK18 was significantly higher in the NAFLD group (19.01±3.49 ng/ml) versus the HCV group (8.95±1.06 ng/ml) and the control group (4.83±1.6 ng/ml) (P<0.001). The CK18 levels in biopsy stages (steatosis, ballooning, inflammation, and fibrosis) and FibroScan/CAP degrees showed that CK18 increased significantly with steatosis and fibrosis stages (biopsy or FibroScan/CAP), but did not reach significance with ballooning or inflammation grades. CK18 was significantly different in nonalcoholic steatohepatitis versus non-nonalcoholic steatohepatitis patients (P=0.041). The best CK18 cutoff to detect steatosis (S≥2) in NAFLD and HCV was 11.65 and 6.84 ng/ml, respectively with an overall sensitivity and specificity over 97%. The CK18 cutoff for significant fibrosis (F≥2) by FibroScan in the NAFLD/HCV groups was 9.115 ng/ml, with 62.5%/69.2% sensitivity/specificity (P=0.031). However, inflammation had a cutoff with a marginal P value (P=0.080), and a reliable cutoff for ballooning was not attained (P=0.386). There was a positive correlation between CK18 and fibrosis (by FibroScan) in the NAFLD and HCV groups (P<0.05). The correlation between CK18 and steatosis in CAP and the nonalcoholic fatty liver disease activity score was very good (P<0.001).
Serum CK18 is related strongly to the development/progression of NAFLD and HCV-related fibrosis/steatosis. TE was correlated highly with liver biopsy results. The combination of CK18 with other noninvasive modalities increases the diagnostic yield of these tests.
非酒精性脂肪性肝病（NAFLD）已成为全球慢性肝病最常见的病因。人们对多种用于NAFLD的诊断性非侵入性方法（血清学和影像学方法，单独或联合使用）进行了研究。细胞角蛋白-18（CK18）作为诊断NAFLD和丙型肝炎病毒（HCV）患者脂肪变性/纤维化的一种新型血清学标志物受到关注。
本研究旨在评估NAFLD和HCV纤维化/脂肪变性患者的血清CK18，并将其性能与瞬时弹性成像（TE）和受控衰减参数（CAP）在诊断这些患者纤维化/脂肪变性时的诊断准确性进行关联。
纳入三组等量参与者（n = 135）：第一组包括慢性HCV患者，第二组包括NAFLD患者，第三组包括对照参与者。对所有组进行TE/CAP检查以及包括血清CK18在内的实验室检查。对NAFLD组进行肝活检。
NAFLD组血清CK18（19.01±3.49 ng/ml）显著高于HCV组（8.95±1.06 ng/ml）和对照组（4.83±1.6 ng/ml）（P<0.001）。活检阶段（脂肪变性、气球样变、炎症和纤维化）以及FibroScan/CAP程度中的CK18水平显示，CK18随脂肪变性和纤维化阶段（活检或FibroScan/CAP）显著升高，但在气球样变或炎症分级中未达到显著水平。非酒精性脂肪性肝炎患者与非非酒精性脂肪性肝炎患者的CK18有显著差异（P = 0.041）。在NAFLD和HCV中检测脂肪变性（S≥2）的最佳CK18临界值分别为11.65和6.84 ng/ml，总体敏感性和特异性超过97%。NAFLD/HCV组中FibroScan诊断显著纤维化（F≥2）的CK18临界值为9.115 ng/ml，敏感性/特异性为62.5%/69.2%（P = 0.031）。然而，炎症的临界值P值接近显著水平（P = 0.080），未获得可靠的气球样变临界值（P = 0.386）。NAFLD和HCV组中CK18与纤维化（通过FibroScan）呈正相关（P<0.05）。CK18与CAP中的脂肪变性以及非酒精性脂肪性肝病活动评分之间相关性非常好（P<0.001）。
血清CK18与NAFLD以及HCV相关纤维化/脂肪变性的发生/进展密切相关。TE与肝活检结果高度相关。CK18与其他非侵入性检查方法联合使用可提高这些检查的诊断率。
