Background:  Osteopontin (OPN) is an important tumor marker, since it presents as an immobilized extracellular matrix molecule in addition to be present as a secreted form in body fluids involving plasma. Osteopontin levels in the plasma were found to be significantly higher in hepatocellular Carcinoma (HCC) patients than in healthy control individuals and also higher than in patients with chronic liver diseases. Dikkopf related protein-1 (DKK-1) is a diagnostic and prognostic serologic marker for early HCC.  The DKK-1 mRNA and protein levels were found to be up regulated in early HCC.
Study design: This is a retrospective case control study.
Objective: The aim of the present study was to evaluate the role of serum OPN level and Dickkopf-1(DKK1) as potential markers of HCC among HCV infected patients, compared to alpha fetoprotein (AFP). Also, its relationship with clinicopathological features of HCC patients.
Subjects and Methods: The study included 90 adult subjects; they were classified into 3 groups.  Group1: It included 30 patients with HCC. Group 2: It included 30 patients with chronic liver disease (CLD) (chronic hepatitis C without HCC), and Group 3: It included 30 apparently healthy individuals as a control group. Serum Osteopontin and Dikkopf related protein -1(DKK-1) were measured by Enzyme-linked immunosorbent assay ELISA.
Results: There were highly statistical significant differences between the three groups as regard serum Dikkopf related  protein -1 and Osteopontin levels (p <0.001). DKK1 and OPN levels were significantly higher in metastasis cases than non-metastatic cases (p <0.001), while AFP level was non-significant P= 0.424. Patients with large tumor size have significantly higher OPN levels p=0.025, while non-significantlydifferent as regard AFP and DKK1 levels.
Conclusion:  OPN and DKK1 can be used for diagnosis of HCC and differentiation between HCC and CLD. OPN and DKK1 have higher sensitivity and specificity than AFP and can be used for early diagnosis. Combination between OPN and DKK1  has increased both sensitivity and specificity for detection of of HCC.