الفهرس 
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Abstract
Hepatocellular carcinoma is the most common primary liver cancer, and its incidence has clearly arisen by the prevalence of major risk factors mainly HBV and HCV. chronic liver patients at the stage of extensive fibrosis or cirrhosis are more susceptible to develop HCC. The monitoring programs of these patients have allowed early detection of disease management to promote a radical therapy.
Alpha fetoprotein, in clinical practice, is not a sufficiently reliable marker to identify HCC patients due to its poor sensitivity. So a need for other tests for the diagnosis and screening of patients at risk of HCC is an important.
Midkine and GP73 are identified as important potential novel biomarkers for early detection of HCC.
The aim of this study was to estimate serum MDK and GP73 levels in HCC diagnosis and to examine their correlation with the laboratory tests, radiological and pathological parameters in diagnosis of HCC.
The study was conducted on 96 subjects divided into three groups; group I: HCC group (40), group II: CLD group (36) and group III: control group (20). Patients were selected from inpatients and outpatient clinic of the Tropical Medicine Department-Menoufia University Hospital, Oncology Clinic, Liver Institute, Menoufia University and Shebin El-Koom Teaching Hospital in the period from September 2015 to July 2016.
Patients and controls were subjected to careful medical history, full clinical examination and laboratory investigations, including complete blood picture, liver function tests, renal function tests, viral markers and serum AFP MDK and GP73 levels. The data were collected, tabulated, and analyzed.
The results of this study revealed that:
- The serum levels of MDK and GP73 were significantly elevated in CLD and more elevated in HCC cases. There was a highly significant difference (p<0.001) between HCC and CLD groups and between HCC and control groups regarding AFP, MDK and GP73. There was a highly significant difference (p<0.001) between CLD and control groups regarding MDK and GP73 but there was no significant difference (p > 0.05) regarding AFP.
- There was non-significant differences between AFP serum levels in patients with different types of BCLC, CTP score and MELD score. On the other hand, there was a significant differences (P <0.05) between BCLC A and BCLC B and also between BCLC A and BCLC C as regard GP73 serum levels. Also, Serum level of GP73 increased from Child A to Child B but with no statistically significant difference.
- There was non-significant difference (p > 0.05) in the levels of AFP, MDK and GP73 serum levels in relation to lymph node involvement, portal vein invasion and tumor size, but their levels increased as the disease became advanced.
- There were significant positive correlations (p<0.05) between AFP with HB and total bilirubin and a negative correlation
between AFP with platelet was present but without significance (p>0.05).
- There were high significant positive correlations (p<0.001) between MDK with AST, total bilirubin, urea and creatinine and a high significant negative correlation (p<0.001) with platelet, a significant negative correlation with prothrombin concentration (p<0.05) and a negative correlation with albumin without significance (p>0.05).
- There was a high significant positive correlation between GP73 with AST, total bilirubin and urea (p<0.001), a significant positive correlation with creatinine, a significant negative correlation (p<0.05) with platelet and prothrombin concentration and a negative correlation with albumin without significance (p>0.05).
- The optimal diagnostic cut-off for MDK by ROC curve was 1585.0 pg/ml, with a sensitivity of 100% and specificity 88.9%, PPV 90.9%, NPV 100% and overall accuracy of 94.7%. Also, the optimal diagnostic cut-off for GP73 was 42.5 ng/ml giving a sensitivity of 90% and specificity 83.3%, PPV 85.7%, NPV 88.2% and overall accuracy of 86.8%.
- With the evaluation of AFP, MDK and GP73 among the early HCC group; AFP had an AUC of 0.730 and P value of 0.002, at or more than a cutoff value of 17.6 ng/ml, so AFP can diagnose early HCC with sensitivity 66.7%, specificity 76.9% and PPV 40%, NPV 90.9% and overall accuracy of 75%. MDK had an AUC of 0.869 and P value of <0.001, at or more than a cutoff value of 3825 pg/ml, so MDK can diagnose early HCC with sensitivity 88.9%, specificity 79.5% and PPV 50%, NPV 96.9% and overall
accuracy of 81.3%. GP73 had an AUC of 0.941 and P value of <0.001, at or more than a cutoff value of 84.5 ng/ml, so GP37 can diagnose early HCC with sensitivity 94.4%, specificity 83.3% and PPV 56.7%, NPV 98.5% and overall accuracy of 85.4%.
- In conclusion, MDK and GP73 expression increased in HCC patients and their diagnostic performance was superior to that of AFP especially at an early stage.