الفهرس 
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Abstract
Liver cancer was ranked the fifth cancer among cancers and the second as regards cancer-related death worldwide, with 854,000 new cases and 810,000 deaths annually, causing about 7% of all cancers. Hepatocellular carcinoma (HCC) constitutes about 90% of primary liver cancers and forms a great global health problem. chronic Hepatitis C (CHC) is a major risk factor for the development of cirrhosis and subsequent hepatocellular carcinoma.
Early stage of HCC can be managed with curative procedures, such as resection, percutaneous ablation and transplantation. Thus, there is a critical need to identify better methods for detecting and recognizing these lesions in order to improve the prognosis of HCC patients.
The problem with AFP as a dependable HCC biomarker is that HCC is the positivity of AFP is only 60%-80% in patients of HCC, and false-positives make many difficulties in differentiation between early stage HCC from other liver disorders, such as chronic hepatitis, cirrhosis, as well as other tumors outside the liver.
In normal liver and patients with chronic hepatitis, ANXA2 is almost undetectable. On the other hand ANXA2 is overexpressed in HCC; moreover patients with early stages of HCC have elevated levels of ANXA2 even if these patients have normal levels of AFP.
Plasma osteopontin levels are higher in HCC patients than healthy controls and in patients with chronic liver diseases.
The aim of this work is to evaluate the role of annexin A2 and osteopontin for early diagnosis of hepatocellular carcinoma in hepatitis c virus patients.
The study was carried out on 80 patients classified into two groups. group A 40 chronic hepatitis C patients while, group B 40 HCC patients. Patients with Other malignancy, diabetes mellitus, renal failure, any bony lesions, other viral hepatitis and stages B, C and D (late HCC) are excluded.
All patients were subjected to the following:
1. Detailed history and thorough clinical examination.
2. Laboratory ivestigations including
a. Routine investigations :
• Complete blood picture and fasting blood glucose.
• Blood urea and serum creatinine.
b. Liver function tests and liver enzymes including serum alanine transaminase, serum aspartate transaminase, serum albumin, serum bilirubin, prothrombin activity, alkaline phosphatase and gamma glutamyl transferase.
3. HCV Ab, HCV RNA and HBsAg.
4. Estimation of serum alpha-fetoprotein.
5. Abdominal ultrasonography and Triphasic CT liver.
6. Serum level of osteopontin using ELISA
7. Serum level of annexin A2 using ELISA
Statistical analysis of data obtained from the present study revealed the following results:
• As regards liver enzymes, AST and GGT were statistically significantly higher in HCC group than chronic hepatitis C group.
• Liver function tests showed albumin and prothrombin activity were statistically significantly lower in HCC group than chronic hepatitis C group. Serum bilirubin was statistically significantly higher in HCC groups than chronic hepatitis C group.
• Serum alpha-fetoprotein was found to be statistically significantly higher in patients with HCC group than chronic hepatitis C group.
• Serum osteopontin was found to be statistically significantly higher in patients with HCC group than chronic hepatitis C group.
• Serum annexin A2 was found to be statistically significantly higher in patients with HCC group than chronic hepatitis C group.
• In HCC group there was statistically significant positive correlation between OPN level and serum bilirubin (total and direct).
• In HCC group there was statistically significant positive correlation between annexin A2 level and alkaline phosphatase. Also there was significant relation was noted between annexin A2 level and fatigue, abdominal pain and vomiting.
• The ROC curve for AFP was significant, its diagnostic performance was 0.818* (p<0.001*), the cutoff point 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 %.
• The ROC curve for OPN 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 %.
• The ROC curve for ANXA2 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 %.
• Using a combination of OPN at 13.2 (ng/ml) and AFP at 6 (ng/ml), increased the specificity to 85%, but decreased the sensitivity to 70% and the accuracy to 77.50%.
• Using a combination of ANXA2 at 10.1 (ng/ml) and AFP at 6 (ng/ml), increased the sensitivity to 82.5%, the specificity to 92.5%, and the accuracy to 87.5%.
• Using a combination of OPN at 13.2 (ng/ml) and ANXA2 at 10.1 (ng/ml), increased the sensitivity to 92.5%, the specificity to 92.5%, and the accuracy to 92.5%.
• Using a combination of OPN at 13.2 (ng/ml), ANXA2 at 10.1 (ng/ml), and AFP at 6 (ng/ml), increased sensitivity to 87.5%, specificity to 92.5%, and accuracy to 90.0%.
• Osteopontin was found to have better specificity but lower sensitivity, diagnostic performance and accuracy than serum AFP for detection of early HCC in patients with chronic hepatitis C.
• Annexin A2 was found to have better diagnostic performance, sensitivity, specificity, positive predictive value, negative predictive value and accuracy than AFP so it could be developed as an effective diagnostic and predictive marker for early HCC in patients with chronic hepatitis C.
• Using combination of serum osteopontin and annexin A2 represent the best diagnostic performance, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for detection of early HCC in patients with chronic hepatitis c