Background: Liver cancer is the fifth most common cancer and the second most frequent cause of cancer-related death globally. Early stages of hepatocellular carcinoma (0&A) can be treated with curative procedures. The aim of this work was to evaluate the role of annexin A2 and osteopontin for early diagnosis of hepatocellular carcinoma in hepatitis C virus patients. Methods: The study was carried out on 80 patients classified into two groups. Group A had 40 chronic hepatitis C patients without hepatocellular carcinoma, while group B had 40 chronic hepatitis C patients with early hepatocellular carcinoma (stages; 0&A). All patients were subjected to thorough history taking, clinical examination, liver function tests, renal function tests, serum alpha-fetoprotein, serum osteopontin, and serum annexin A2. Results: Serum alpha-fetoprotein was found to be statistically significantly higher in patients with the hepatocellular carcinoma group than the chronic hepatitis C group. The ROC curve for alpha-fetoprotein for detection of HCC was significant, its diagnostic performance was 0.818 * (p < 0.001 *), and the cutoff point for predicting the probability for HCC was 6.0 (ng/ml) with sensitivity of 77.50%, specificity of 82.50%, positive predictive value of 81.60%, negative predictive value of 78.6%, and accuracy of 80%. Serum osteopontin was found to be statistically significantly higher in patients from the hepatocellular carcinoma group than the chronic hepatitis C group. The ROC curve for osteopontin was significant, its diagnostic performance was 0.739 * (p < 0.001 *), the cutoff point was 13.2 (ng/ml) with sensitivity of 65.0%, specificity of 90.0%, positive predictive value of 86.70%, negative predictive value of 72.0%, and accuracy of 77.0%. Serum annexin A2 was found to be statistically significantly higher in patients from the hepatocellular carcinoma group than the chronic hepatitis C group. The ROC curve for annexin A2 was significant, its diagnostic performance was 0.927 * (p < 0.001 *), the cutoff point was 10.1(ng/ml) with sensitivity of 85.0%, specificity of 85.0%, positive predictive value of 85.0%, negative predictive value of 85.0%, and accuracy of 85.0%. Conclusions: Osteopontin had better specificity but lower sensitivity than serum alpha-fetoprotein for early diagnosis of hepatocellular carcinoma. Annexin A2 had better diagnostic sensitivity and specificity than alpha-fetoprotein for early diagnosis of hepatocellular carcinoma.
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