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Abstract Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and it is one of the major causes of death, because of its high frequency and poor prognosis. It’s the cause of about one million deaths annually allover the world. HCC is now a rather common malignancy in Egypt which usually develops on top of liver cirrhosis secondary to viral infection either hepatitis B or C viruses which are considered as definite risk factors for HCC. Because of the high prevalence rate of HCV in cirrhotic Egyptian patients, it accounts for most HCC cases in Egypt. When far advanced, HCC generally presents with symptoms and physical signs and diagnosis is easy, but before this late stage is reached, clinical diagnosis is often difficult. Conventional tests of hepatic function don’t distinguish HCC from other hepatic masses or from cirrhosis. Accordingly, they contribute little to the diagnosis of the tumor. Diagnosis of HCC depends mainly on the detection of tumor markers in the sera of the HCC patients in addition to other diagnostic modalities such as ultrasound, spiral CT and liver histopathology by biopsy. Tumor markers are substances synthesized and secreted by the malignant cells. They are not normally present in serum and if present they are not biologically active. Few tumor markers are produced in a sufficient large proportion, so they can be used as serum markers of tumors and they become helpful in screening, diagnosis and follow up of cases. Serum AFP concentrations have been shown to be the most useful tumor marker with regards to HCC but it may be normal in up to 40% of patients (lack of sensitivity). It may be increased in hepatitis and cirrhotic patients (lack of specificity). The availability of a more sensitive serological marker that distinguishes between HCC and benign hepatic lesions would therefore, be very useful for early and specific diagnosis. Chromogranin-A (Cg-A) is a 49-KDa acid glycoprotein originally described in catecholamine storage vesicles of the adrenal medulla. It has a wide distribution in secretory vesicles of the endocrine, neuroendocrine and nervous systems, where it is costored and co-secreted with hormones and neurotransmitters. It is present in low concentration in the serum of healthy individuals and in high concentration in patients with renal failure and heart failure. Clusters of cells containing Cg-A have been demonstrated within HCC tissues. Previous studies reported high serum Cg-A values in patients with HCC suggesting that Cg-A might represent a useful marker for HCC and a complementary diagnostic tool, unless kidney or heart failure is present. The aim of this study was to investigate the diagnostic utility of plasma Cg-A in patient with liver cirrhosis and HCC in comparison to the conventional markers, namely serum albumin, PT and INR in cirrhotic patients and AFP in HCC. Our study was conducted on 60 patients who presented to the Tropical Department of Ain Shams University Hospitals and National Liver Institute in Monofyia University. The patients’ group included: group 1 (30 patients with primary HCC) and group 2 (30 patients with liver cirrhosis). In addition, 20 age- and sex-matched healthy subjects were included as control group.All subjects included in this study were subjected to full history taking, clinical examination, radiological investigations including CT scan and abdominal ultrasound for patients, laboratory investigations including CBC, prothrombin concentration, INR, renal function (urea and creatinine), liver function (ALT, AST, albumen, ALP and bilirubin), hepatitis markers (HBs Ag and HCV Abs), AFP and Cg-A. Regarding AFP and Cg-A, both were significantly higher in HCC patients compared to cirrhotic patients and control group, respectively. However, a non significant difference was observed between cirrhotic patients and control group regarding both markers. Our correlation study between AFP and other studied parameters in all groups revealed a non significant correlation with the exception of ALP which correlated positively with AFP in HCC group. The correlation analysis between Cg-A and other studied parameters in all groups also revealed a non significant correlation.Regarding the diagnostic performance of AFP for discriminating HCC patients versus cirrhosis and control, the best cut-off value was 22.8ng/mL. This had a diagnostic sensitivity of 87%, specificity 100%, positive predictive value 100%, negative predictive value 93% and a diagnostic efficiency 95%. On the other hand, the best cut-off value of Cg-A for discriminating HCC patients versus cirrhosis and control was 53ng/mL. This had a diagnostic sensitivity of 87%, specificity 86%, positive predictive value 79%, negative predictive value 92% and a diagnostic efficiency 86%. The combined use of the two markers, AFP and Cg-A, led to increase the sensitivity to 97% and increase the specificity to 100%. This showed that simultaneous measurements of serum AFP and Cg-A are of value in detecting HCC. In conclusion, Cg-A was proved to be significantly higher in HCC patients compared to cirrhotic patients and control group. Therefore, it can be used as a potential serologic marker for HCC and a complementary diagnostic tool in monitoring cirrhotic patients for detection of HCC. An observation worth further investigation is that the combined use of AFP and Cg-A increase the diagnostic performance for detection of HCC which suggested that the inclusion of Cg-A to the current standard tests for detection of HCC may improve the ability to identify patients who might be missed by current diagnostic strategies and thus might provide a better therapeutic outcome . |