Diagnostic Outcomes of Soluble Major Histocompatibility Complex Class I Related Chain Molecule A and Des-γ Carboxy Prothrombin versus AlphaFetoProtein for Hepatitis C Virus-Induced Hepatocellular Carcinoma in Egyptian Patients

Abstract
Objectives: Hepatitis C virus (HCV) infection is a major threat for developing hepatocellular carcinoma (HCC) in Egypt which represents an increased cause of mortality. HCC usually presents at a very late stage thus many patients miss the best opportunity for treatment because of lack of early symptoms and early reliable diagnostic marker for malignant transformation. This study aimed to perform a head-to-head comparison of the diagnostic performance of soluble major histocompatibility complex class I related chain molecule A (sMICA), Des-γ Carboxy Prothrombin (DCP) and Alpha-Feto Protein (AFP) in HCC patients.

Subjects and methods: The study included 250 subjects. They were including 50 chronic hepatitis patients, 50 cirrhotic patients, 100 patients with HCC on top of cirrhosis and 50 apparently healthy control subjects. HCC group was subdivided into two subgroups, 61 patients with tumor size from 2 to 5 cm and 39 patients with tumor size >5cm. Serum levels of sMICA, DCP as well as AFP were measured in the sera of all subjects by Enzyme Immune Assay (EIA).

Results: AFP, DCP and sMICA showed statistical significant increased levels in HCC group when compared to other groups (p<0.05). However, there was a highly significant increase in AFP levels in other patients groups when compared to control group (p ≤ 0.001). There was no significant difference in DCP level between chronic hepatitis and liver cirrhosis groups and as well when both were compared to the control group. sMICA levels were mostly increased in HCC patients in comparison to healthy or disease controls (p ≤ 0.001). The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the diagnostic efficacies of sMICA, DCP and AFP. When employing the ROC curve, the superiority of sMICA [AUC: 0.928] to both AFP [AUC: 0.886] and DCP [AUC: 0.656] was evident in the diagnosis of HCC, in discriminating HCC from LC and CH patients [AUC: 0.908] as well as in discriminating HCC with small focal lesions (tumor size from 2-5cm) from both cirrhotic and CH patients [AUC: 0.917 & sensitivity: 88.5%]. The sensitivity of sMICA was the highest (88.5%) versus (62%) for AFP and (54%) for DCP.

 
Conclusion: sMICA levels showed a stepwise increase from CH to LC and up to the most in HCC. However, AFP levels were increased in HCC and other chronic liver diseases while DCP levels were increased only in HCC. As well, sMICA has superior diagnostic performance for HCV-induced HCC on both AFP and DCP with even better performance for distinguishing HCC with small focal lesions. Consequently, measurement of sMICA as a single marker or beside AFP and/or DCP may be valuable in the screening for early malignant transformation of chronic liver diseases to HCC.