Abstract Background Egypt has the highest hepatitis C virus (HCV) prevalence worldwide. Cirrhosis secondary to HCV is associated with the highest annual risk for developing hepatocellular carcinoma. The burden of HCC has been increasing in Egypt with a doubling in the incidence rate in the past 10 years. HCC contributes to 14.8% of all cancer mortality in Egypt. Most HCCs (80%) arise in a cirrhotic liver, a situation where there has been longstanding hepatocyte damage and chronic inflammation leading to fibrosis. Aim of the Work This study aims to evaluate the diagnostic value of plasma mSEPT9 assay in detection of HCC in Egyptian patients with post hepatitis C liver cirrhosis in comparison to serum level of α-fetoprotein (AFP). Patients and Methods This is a prospective case-control study conducted at the Gastroenterology department in Ain Shams University Hospital. The study population consisted of 80 subjects, divided into three groups: 40 patients with hepatocellular carcinoma, 20 patients with liver cirrhosis, and 20 healthy subjects as controls with matched age and gender. Results The study found that hepatocellular carcinoma (HCC) was more frequent in male patients and that the age of HCC patients was statistically significantly higher than patients with cirrhosis and healthy controls. Patients with HCC and cirrhosis had a higher Child Pugh score than healthy controls. Portal hypertension and portal vein thrombosis were more frequent in HCC and cirrhosis patients than in the control group. Liver enzymes were higher in patients with HCC and cirrhosis compared to healthy controls, while hemoglobin and platelet levels were lower in patients with HCC. Hepatitis C antibody and PCR were positive in HCC and cirrhosis patient groups. AFP and Methylated Septin 9 levels were higher in patients with HCC and cirrhosis than in healthy controls, and AFP had better diagnostic accuracy than Methylated Septin 9. Both AFP and Methylated Septin 9 levels were positively correlated with age, Child Score, liver enzymes, and coagulation profile and negatively correlated with platelet count and hemoglobin level. AFP level was positively correlated with the number of focal lesions and liver size. Conclusion This study demonstrated that plasma Methylated Septin 9 can be a promising noninvasive and circulating epigenetic biomarker for HCC diagnosis at the individual level. However, our results showed that AFP was superior than Methylated Septin 9 in the detection of HCC, Methylated Septin 9 has higher Sensitivity. It was suggested that the combination of plasma mSEPT9 and AFP could enhance the sensitivity of Methylated Septin 9 or AFP alone in the diagnosis of HCC. Further comparative studies with larger sample size and longer follow-up are needed to confirm our results and to identify risk factors of adverse events.
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