الفهرس 
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Abstract
Hepatocellular carcinoma is the most common cause of primary liver neoplasms. The major risk factors associated to the development of HCC are viral infection with hepatitis B virus(HBV), hepatitis C virus(HCV), and cirrhosis. HCC is one of the main causes of death in patients with liver cirrhosis
Alpha fetoprotein serum levels have been found in 60-70% of patients with HCC; nevertheless, there are other causes that increase this protein such as cirrhosis, lung cancer, biliary cancer, gastric cancer, pancreatic cancer, teratocarcinoma of the testis, and tyrosinemia.
LAG-3 is a surface receptor expressed by activated CD8+T-lymphocytes, this expression is maintained for an extended period during persistent virus infections, typically for as long as the Ag is present.
LAG-3 has been observed in various cancer types. Its expression in HCC play a role in the suppression of antitumor immunity in HCC and provide a basis for investigating combinatorial checkpoint blockade with a LAG-3 and PD-L1 inhibitor in HCC.
The present study was carried out in the Clinical Pathology Department and department of Tropical, Faculty of Medicine, El-Minia University Hospital. It was conducted through the period from December, 2018 to March, 2019. The aim of this study was to asses the expression level of LAG3 on peripheral blood CD8+T lymphocytes in chronic HCV patients, liver cirrhosis, and HCV induced HCC patients, as well as to study the diagnostic value of LAG3 expression on CD8+T lymphocytes in diagnosis of HCC and liver cirrhosis.
The study included 25 patients with hepatocellular carcinoma, 25 patients with liver cirrhosis, 25 chronic hepatitis patients, and 25 apparently healthy volunteers who served as a control group.
Hence the study subjects were divided into the following groups:
group I: It included 25 patients suffering from HCV induced HCC, they were 20 males and 5 females, with ages ranged from 45 to 68 years old with mean±SD(57.8±6.1).
group II: It included 25 pateints suffering from HCV induced liver cirrhosis, they were 11 males and 14 females, with ages ranged from 50 to 70 years old with mean±SD (59.1±5.1)
group III: It consisted of 25 patients suffering from chronic HCV infection without cirrhosis or HCC, they were 15 males and 10 females, with ages ranged from 40 to 65 years old with mean±SD(48.9±5.4).
group IV: It consisted of 25 apparently healthy volunteers who served as control subjects. They were matched in age and sex.
The results of this study were summarized as follows:
Alpha-fetoprotein (AFP) level was significantly increased in group I when compared with groups III and IV, while there was a non-significant difference comparing group I and II. Also, AFP was significantly increased in group II when compared to groups III and IV.
CD8 % was significant up regulation in group I compared to group III and IV. While there was no significant difference between group I and II. In group II CD8% was significantly increased when compared to group IV, while this increase was non significant when compared to group III. group III showed a significant increase in CD8 % when compared to group IV.
The frequency of LAG-3 expression was significantly increased comparing group I to group III and IV, while this increase was non-significant when compared group I with group II. group II showed a non-significant increase in LAG3 expression when compared to group III, while this increase was significant when compared to group IV. There was a non-significant difference in LAG3 expression when compared group III with group IV.
By using the receiver operating characteristic(ROC) curve, the results of the present study showed that co-expression of LAG3 on CD8+ T cells had a high sensitivity of 90.9% and NPV of 80.7%, in HCC group patients versus the diseased and healthy controls, which was higher than that in AFP which had a sensitivity of 76% and NPV of 70.9%. Also, the frequency of LAG3 in HCC patients versus the diseased and healthy controls, showed a specificity of 77.3%, PPV of 71.9%, and NPV of 77.3%, which was better than AFP that showed a specificity of 58.7%, PPV of 64.7%, and NPV of 70.9%.
LAG3 expression in cirrhosis group versus CHC patients and controls showed a sensitivity of 72%, specificity of 88%, PPV of 85.7%, and NPV of 75.8%. which was higher in comparison with AFP showing a sensitivity of 52%, specificity of 80%, PPV of 72.2%, and NPV of 62.5%.