Background/Aim of the work: Cytokeratin 18 (CK18) is the major intermediate filament protein in the liver and one of the most prominent substrates of caspases during hepatocyte apoptosis, which plays a pivotal role in acute as well as in chronic liver diseases. The aim of this study was to determine serum caspase-cleaved CK18 level in patients with HCV-related chronic liver disease and hepatocellular carcinoma (HCC) and to explore its relation to other clinical & biochemical parameters in this patients , and its possible diagnostic value. Patients and methods: This study was carried out on 80 Patients, they were categorized into 3 groups: Group I: included 40 patients with chronic HCV (CHC), liver biopsy was done for them and histological diagnosis was assessed according to Metavir classification. Group II: included 20 patients, post-CHC cirrhosis. Group III: included 20 patients post-HCV HCC. The sera of patients and 13 healthy volunteers served as a control for parallel evaluation of CK-18 (a proteolytic neoepitope of the caspase) by ELISA. Results: CK-18 fragment levels showed a significant positive correlation with Metavir activity grade(P 0.01), as well as viral load (P 0.02) in CHC group, but there was no significant difference between those with normal or high alanine aminotransferase (ALT) P value 0.116. While there was neither significant correlation with fibrosis stage in CHC group, nor Child , MELD and uMELD scores for groups II & III. CK-18 fragments were significantly increased in patients with HCC, mean ± DS(399.1±301.1), and in range of (100.97-1064.4). It was significantly higher than the control and both CHC and cirrhotic groups (P value 0.000 for all). But there was neither correlation with OKUDA classification, nor with α-fetoprotein serum levels. While α fetoprotein was significantly higher in HCC group in relation to control and CHC group ( P values 0.013 & 0.041 respectively). In diagnosis of patients with HCC, the area under the ROC curve (AUC) was estimated to CK-18 fragments, it was 0.909 ( CI 0.847-0.971) at cutoff 119.3 Pg /mL with 95% & 70.4% for sensitivity and specificity respectively . It was better than that based on α-fetoprotein, where AUC was 0.834 (CI 0.719- 0.949) at cutoff 12.2 Pg /mL with 70% & 86% for sensitivity and specificity respectively. CONCLUSIONS: Serum CK-18 is elevated in patients with non-malignant as well as malignant liver diseases, particularly in those with prominent cytolysis. Further studies are needed to evaluate the use of CK-18 as a marker of liver disease. |
