Clinical Utility of Cytokeratins for Accurate Diagnosis of Hepatocellular Carcinoma Among Hepatitis C Virus High-Risk Patients

Abstract

Objectives: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and a global health problem. It is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. Cytokeratins are a marker of hepatic progenitor cells and act as a key player in tumor invasion. Herein, we sought to develop a novel score based on the combination of cytokeratin 18 (CK18) and cytokeratin 19 (CK19) with routine laboratory tests for accurate detection of HCC.

Material & methods: Serum CK18, CK 19, α-fetoprotein, albumin and platelets count were assayed in HCC patients (75), liver cirrhosis patients (55) and healthy control (20). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named CK-HCC = CK 19 (ng/ml)×0.001+ CK18 (ng/ml)×0.004 + AFP (U/L)×5.4 - Platelets count (×109)/L×0.003 - Albumin (g/L)×0.27-36 was developed. CK-HCC score produces AUC of 0.919 for differentiating patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 1.3 (i.e., less than 1.3 the case is considered cirrhotic, whereas above 1.3 it is considered HCC.

Conclusion: CK-HCC score could replace AFP during screening of HCV patients and early detection of HCC.

Keywords: Cytokeratins; Diagnosis; HCV; Hepatocellular carcinoma.

Figure 1

Area under Curve (AUC) of Biomarkers to Discriminate Patients with HCC from Cirrhotic Patients

Figure 2

Box Plots of CK-HCC Score to Discriminate HCC Patients from Those with Liver Cirrhosis as well as Healthy Control. The box represents the interquartile rang. The whishkers indicates the highest and lowest values, and the line across the box indicates the medium value

Figure 3

ROC Curve of CK-HCC Score and AFP for Discriminating Patients with Hepatocellular Carcinoma from those with Liver Cirrhosis (AUCs were 0.919 and 0.692, respectively

Figure 4

Area under ROC Curve (AUC) of CK-HCC Compared with AFP for early Diagnosis of HCC with Tumor Burden Feature Including Number of Hepatic Lesion, Vascular Invasion, Tumor Size, Tumor Grade, Tumor Encapsulation and TNM Stage