الفهرس 
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Abstract
HCC is the most common primary liver cancer. Its incidence is clearly arising by the prevalence of major risk factors mainly hepatitis B and hepatitis C. The population at risk is composed of chronic liver patients at the stage of extensive fibrosis or cirrhosis. The monitoring programs of this population have allowed early detection of disease to promote a radical therapy.
Alphafeto-protein, available in clinical practice, is not a sufficiently reliable marker to identify HCC patients, mainly due to its poor sensitivity. So the need for other tests for the diagnosis and screening of patients at risk of HCC.
Therefore, identification of new specific and sensitive biomarkers for early diagnosis is urgently needed. Many alternative novel biomarkers, such as AFP-L3, DCP, GP73, and GPC3, have been investigated; however, their diagnostic values about early hepatocellular carcinomas remain controversial. Thus, it is necessary to identify new serologic biomarkers with both sufficient sensitivity and specificity to detect hepatocellular carcinomas at an early stage and/or with negative AFP.
Midkine was identified as 1 of the 5 important potential novel biomarkers for early detection of hepatocellular carcinomas.
The aim of the study is to evaluate the clinical significance of serum Midkine levels in the diagnosis of hepatocellular carcinoma and compare it to alpha-fetoprotein.
The study was conducted on 90 subjects divided into three groups. Group I (HCC Group), Group II (Liver Cirrhosis Group) and
Summary
Group III (Control Group) included 50, 20 and 20 patients, respectively.
All patient and control groups were subjected to the following: full history taking, thorough clinical examination, abdominal ultrasonogrphy, and ultrasound guided liver biopsy was performed by true-cut needle or liver biopsy gun for the cirrhotic patients when possible, triphasic C.T. to patients with focal lesion. The following laboratory investigations were done: liver function tests including: ALT, AST, serum albumin, total and direct bilirubin , prothrombin concentration and INR, serum AFP and hepatitis markers (HBsAg, anti-HBc and HCV antibody). Determination of Midkine was determined by ELISA Kit.
The results of this study revealed that:
- The serum levels of Midkine were significantly elevated in chronic liver diseases and more elevated in HCC cases. There is a highly significant difference with comparison between HCC and cirrhotic groups and with comparison between HCC and control groups regarding AFP and Midkine, but with comparison between cirrhotic and control groups regarding AFP and Midkine there is no significant difference.
- In the diagnosis of HCC, AFP had AUC of 0.826 with P value of <0.001. At a cutoff value of 20.2 ng/mL, AFP was 64% sensitive, 85% specific and had PPV of 84.2%, NPV of 65.4% and overall accuracy of 73.3%.
- In the diagnosis of HCC, Midkine had AUC of 1.00 with P value of <0.001. At a cutoff value of 0.60 ng/mL, Midkine was 100% sensitive, 97.5% specific and had PPV of 98.04%, NPV of 100% and overall accuracy of 98.9%.
Summary
- With evaluation of AFP among early HCC group, AFP had AUC of 0.707 and P value of 0.003. At a cutoff point of 19.5 ng/mL, AFP had sensitivity and specificity of 66.7% and 65.2% respectively, PPV was 41.03%, NPV was 84.3% and overall accuracy of 65.6%.
- With evaluation of Midkine among early HCC groups, Midkine had AUC of 0.829 and P value of<0.001. At a cutoff point of 0.92 ng/mL, Midkine had sensitivity and specificity of 91.2% and 66.7% respectively, PPV was 50%, NPV was 95.7% and overall accuracy of 73.3%.
- There is no significant difference with comparison between stages of BCLC regarding AFP and Midkine.
- There is no significant difference with comparison between different size of HCC regarding AFP and Midkine.
- Comparison between presence of PV thrombosis and its absence among HCC group regarding AFP and Midkine shows no significant difference.
- Finally, Midkine expression is highly increased in HCC patients. Its diagnostic performance is superior to that of AFP especially at an early stage.