الفهرس 
Hepatocellular CarcinomaOnly 14 pages are availabe for public view
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Abstract
Liver cancer is the fifth most common cancer and the third most frequent cause of cancer- related death globally. Hepatocellular carcinoma represents about 90% of primary liver cancers and constitutes a major global health problem. Approximately 90% of HCCs are associated with a known underlying etiology, most frequently chronic viral hepatitis (C and B), alcohol intake and aflatoxin exposure. chronic liver disease should be treated to avoid progression of liver cirrhosis and hence HCC. In patients with chronic viral hepatitis, antiviral therapies leading to maintained HBV suppression in chronic hepatitis B and sustained viral response in hepatitis C are recommended, since they have been shown to prevent progression to cirrhosis and HCC development. Surveillance for HCC is recommended in all patients with cirrhosis and has been associated with improved early detection and survival. Although both radiologic tools and serologic markers exist for early diagnosis of HCC, surveillance is currently primarily imaging-based. Guidelines from the American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) recommend surveillance using ultrasound alone. The immune system is a key player in development and progression of cancer disease including HCC, which is capable of recognizing and attacking tumour cells. The identification of mechanisms to escape immune suppression is a major strategy in oncology. Soluble programmed death ligand 1 (sPD-L1) is expressed on resting T cells, B cells, macrophages and dendritic cells, a type I membrane protein that delivers inhibitory signals to T cells. Expression of sPD-L1 is mainly induced by inflammatory cytokines, such as interferon gamma or IL-10. Activation of sPD-1 by its ligands suppresses T cell activation. In hepatocellular carcinoma PD-L1 is expressed by tumour cells. The levels of circulating PD-L1 may have a prognostic value in patients with HCC. HCC is supposed to be a tumour entity susceptible to immunotherapies. Many PD-L1 inhibitors are in development as immunooncology therapies and are showing good results in clinical trials. Clinically available examples include Nivolumab or Pembrolizumab. Our study aimed to investigate the prognostic value of soluble form of programmed death-ligand1 (sPD-L1) in Egyptian hepatocellular carcinoma patients. This is a cross-sectional study that was performed on 85 individuals from the outpatient clinics and inpatients of Tropical Medicine and Infectious Diseases Department at Tanta University Hospitals and divided into four groups: group (I): Included 25 patients with hepatocellular carcinoma without vascular invasion. group (II): Included 25 patients with hepatocellular carcinoma with vascular invasion with or without extra hepatic metastasis. group (III): Included 25 patients with liver cirrhosis group (IV): Included 10 healthy individuals matched in age and sex as controls. In this work, there were no difference in sPD-L1 levels between male and female patients p- value = 0.803 and no significant relationship was found with age r (-0.045), p- value = 0.701. In our study, it was found that sPD-L1 serum levels increased with the stages of cirrhosis and with the stages of HCC. The sPD-L1 levels was higher in patient with HCC and extra hepatic metastasis than patients without extra hepatic metastasis. The sPD-L1 levels in different stages of cirrhosis differed significantly between Child A, B and C patients, with the highest levels found in Child C stage patients (Child A mean 7.524 ng/ml, Child B mean 7.938 ng/ml and Child C mean 9.948 ng/ml. P-value (0.003). The sPD-L1 levels in different stages of HCC according to the Barcelona Clinic Liver Cancer staging system were differed significantly with the highest levels found in BCLC D stage patients. (BCLC A mean 7.845ng/ml, BCLC B mean 9.180 ng/ml, BCLC C 10.970 and BCLC D mean 11.333 ng/ml, P-value (0.001). The correlation between MELD score and sPD-L1 level was statistically significant, r (0.734), p <0.001. (direct correlation). The correlation between CLIP core and sPD-L1 level was statistically significant, r (0.847), p <0.001. (direct correlation). In our study, the correlation between expected median survival and sPD-L1 level statistically significant, r (-0.763), p <0.001.(inverse correlation). In our results, serum sPD-L1 levels differed significantly between ALBI grade, with the highest levels found in Grade 3 (Grade 1 mean 4.993 ng/ml, Grade 2 mean 7.638 ng/ml and Grade 3 mean 10.079, Pvalue (0.001) sPD-L1 level was significantly associated with tumor stage, tumor size, portal vein tumor thrombosis, and venous invasion, suggesting its role as a possible predictive biomarker.