الفهرس 
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Abstract
H
epatocellular carcinoma (HCC), ranks fifth in the frequency of cancers and it is the third-leading cause of cancer related death worldwide. It is usually asymptomatic in the early stages and tends to be invasive.
Hepatitis C virus (HCV) infection, the most common cause of CLD, is estimated to affect 170 million individuals worldwide (2% of the world’s population). The number of Egyptians estimated to be chronically infected is 9.8% and more than 500,000 new HCV infections occur every year.
More than 80% of infected patients develop chronic infection and one-third of these patients develop progressive liver injury, fibrosis, cirrhosis and HCC over a period of 20 to 30 years. Continuous researches are ongoing worldwide to find out and evaluate sensitive and specific new markers for HCC diagnosis.
The diagnosis of HCC is mainly based on a combination of abdominal U/S and serum AFP level. However, small tumors will be missed by abdominal U/S, moreover, serum AFP level lacks tumor specificity and has low sensitivity particularly in early stage disease. Clearly, the available screening methods are inadequate for early detection and follow up of HCC and hence, there is an urgent need for novel biomarkers to increase the sensitivity in early diagnosis of HCC, as well as the specificity in differentiation between HCC and benign lesions.
Clusterin (CLU) was originally identified as a major heterodimeric glycoprotein, expressed in most cells and tissues and is upregulated under a variety of pathological conditions. It’s gene is located on chromosome 8, it has nine exons and at least three isoforms: cytoplasmic and secretory isoforms which prevent cell death and the nuclear isoform which promotes cell death.
There is no doubt nowadays that CLU has an important role in tumorigenesis and progression of human cancers. Many studies have highlighted the role of serum CLU level as a biomarker for various malignant tumours such as pancreatic, breast, colorectal, ovarian, cervical, gastric, bladder, lung, as well as for HCC.
In this regard, the present study aimed to evaluate the clinical utility of serum CLU as a novel biomarker in HCC, to compare it to AFP, the conventional marker of HCC, and to correlate it with the tumor stage.
This study was conducted at the Internal Medicine Department of Ain Shams University Hospital and Shebeen El-Kom Fever Hospital on 15 patients with chronic hepatitis (group I), 15 patients with liver cirrhosis (group II), 40 HCC patients (group III), in addition to 15 apparently healthy, HCV and HBV-seronegative subjects as a control group. Patients in group III were classified according to TNM staging into subgroup IIIa which included (10) patients, subgroup IIIb which included (16) patients and subgroup IIIc which included (14) patients.
All patients in this study were subjected to full history taking, thorough clinical examination, radiological investigations including abdominal U/S and CT scan, routine laboratory investigations including CBC, 2- hours postprandial blood sugar, renal profile (urea and creatinine), liver profile (ALT, AST, ALP, bilirubin and prothrombin time expressed as INR) and viral hepatitis markers (HBs Ag and HCV RNA by real-time PCR). Serum AFP in addition to serum CLU assay was done by using ELISA technique.
Serum AFP showed a highly significant difference between chronic hepatitis group, cirrhosis group and HCC group when compared to control group (P<0.001). However, AFP showed a non significant difference in chronic hepatitis group when compared to liver cirrhosis group (P>0.05). Moreover, a highly significant difference was noticed in HCC group when compared to liver cirrhosis or chronic hepatitis groups (P<0.001).
As regards serum CLU, the results of the present study showed a non-significant difference between the group of chronic hepatitis patients and the control group (P>0.05). However, a highly significant difference was observed between the three studied patients’ groups (P<0.001).
Our correlation study between AFP and CLU revealed a highly significant positive correlation in all groups, with the exception of the cirrhotic group.
Regarding the diagnostic performance of AFP for discriminating HCC patients versus cirrhosis patients, the best cut-off value was 115 ng/mL. This had a diagnostic sensitivity of 100%, specificity 93.3%, positive predictive value 97.6%, negative predictive value 100% and a diagnostic efficiency 98.2%.
On the other hand, the ROC curve analysis of the diagnostic performance of CLU in cirrhosis patients versus the HCC patients revealed a high discriminatory power of the test as evidenced by an area under curve (AUC) of 1 with a wide range of cutoff values from 70-110 µg/mL. These values had a diagnostic sensitivity of 100%, specificity 100%, positive predictive value 100%, negative predictive value 100% and a diagnostic efficiency 100%.
The favorable cutoff level of the AFP in patients with subgroup IIIb and IIIc (grouped together) versus subgroup IIIa was 273 ng/mL. This had a diagnostic specificity of 90%, sensitivity 93.3%, negative predictive value 81.8%, positive predictive value 96.6% and a diagnostic efficiency of 92.5% with an AUC of 0.972. Regarding serum CLU, a cutoff level of 182 µg/mL had a diagnostic specificity of 80%, sensitivity 70%, negative predictive value 47.1%, positive predictive value 91.3% and a diagnostic efficiency 72.5% with an AUC of 0.844.
In conclusion, our results proved the superiority of CLU estimation over AFP assay in differentiating cases of HCC from cirrhosis. However, serum AFP still surpassed serum CLU as a prognostic marker, where it showed better performance in differenciating subgroups of HCC