Abstract Background: Hepatocellular carcinoma is the most com-mon primary hepatic malignancy with an average survival rate of 6-20 months. The primary etiology of hepatocellular carcinoma in Egyptian patients is liver cirrhosis. Alfa fetopro-tein is the most commonly used biomarker for HCC diagnosis, in spite of its low sensitivity and specificity in HCC screening; it is usually combined with ultrasound for early detection of HCC. Leptin is a multifunctional peptide hormone that is produced by adipocytes with neuroendocrine activity. Leptin is postulated to increase the hepatic response to different stimuli of liver fibrosis. The actions of leptin are mediated via hepatic stellate cell activation, and liver fibrosis occurs through its indirect effect on the Kupffer cells. Moreover, it regulates the phosphoinositide 3-kinase/protein kinase B (PI-3K/Pkt) pathway, which plays an essential step in the cell motility, proliferation, survival, and angiogenesis in tumor cells including Hepatocellular Carcinoma (HCC). Thus, leptin can promote HCC proliferation, migration, and invasion. Aim of Study: The present study aimed to evaluate the diagnostic and prognostic value of serum Leptin as a tumor marker in Hepatocellular Carcinoma (HCC) in comparison to Alpha-Fetoprotein (AFP). Subjects and Methods: This study included 180 Egyptian patients that were divided into 4 groups (Group 1: 60 patients with untreated HCC, Group 2: 60 patients with treated HCC, Group 3: 30 patients with end-stage chronic liver disease without HCC) in addition to Group 4: 30 age-matched healthy subjects serving as a healthy control group. All patients and controls were subjected to full history, clinical examination, laboratory investigation, and abdominal ultrasonography (U/S). Serum leptin and alpha-fetoprotein were assayed by using Enzyme-Linked Immunosorbent Assay (ELISA) tech-nique. Results: The results of the present study revealed that serum leptin levels were significantly increased in all the patients' groups when compared to controls; besides, it was significantly higher in untreated and treated HCC patients groups when compared to patient's group without HCC.
Furthermore, serum leptin levels were significantly higher in the patients group with untreated HCC compared to the treated HCC patients group with positive correlation with AFP. Conclusion: AFP was more sensitive and specific in differentiation between cirrhotic patients with or without HCC than Leptin. However, Leptin has a good sensitivity and specificity in differentiating between untreated and treated HCC patients, and it is superior to AFP in the specificity of the differentiation between these two categories. Therefore, serum leptin can be used as a useful screening marker for the diagnosis and prognosis of HCC patients combined with Alfa fetoprotein.