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العنوان
Comparative Study of SIRT1 Expression in Hepatitis B Virus, Hepatitis C Virus, and Hepatocellular Carcinoma Patients /
المؤلف
Ghaly, Antoun Khalil Saad.
هيئة الاعداد
باحث / أنطون خليل سعد غالي
مشرف / أحمد أمين ابراهيم
مشرف / محمد رجب احمد
مشرف / ليلى أحمد راشد
الموضوع
Liver Cancer Congresses. Carcinoma, Hepatocellular.
تاريخ النشر
2021.
عدد الصفحات
148 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الطب الباطني
الناشر
تاريخ الإجازة
9/2/2021
مكان الإجازة
جامعة بني سويف - كلية الطب - الباطنة العامة
الفهرس
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Abstract

Summary
The most common form of primary liver cancer in adults is hepatocellular carcinoma (HCC), and it is the most common cause of death in people with cirrhosis. It occurs in the form of chronic inflammation of the liver and is most closely associated with chronic infection with viral hepatitis (hepatitis B or C) or with exposure to toxins such as alcohol or aflatoxin. The risk of developing HCC is significantly increased by some disorders, such as hemochromatosis and alpha 1- antitrypsin deficiency. As risk factors for HCCC, metabolic syndrome and NASH are also increasingly recognized (Uranbileg et al., 2020).
As with any cancer, according to the details of tumour histology, size, how far the cancer has spread, and overall health, the treatment and prognosis of HCC differ. In Asia and sub-Saharan Africa, in countries where hepatitis B infection is endemic and many are infected from birth, the vast majority of HCC occurs. Owing to a rise in hepatitis C virus infections, the incidence of HCC in the United States and developing countries is growing. For unexplained reasons, it is more common in males than in women (Uranbileg et al., 2020).
A cluster of highly conserved proteins that activate nicotinamide adenine dinucleotide (NAD)-dependent activity of histone deacetylase that target histone and non-histone substrates including enzymes, transcription regulators, tumour suppressors, cell signalling proteins, and DNA repair proteins are the mammalian Sir2 family or sirtuins (Becatti et al., 2014).
There have been seven human sirtuins described and named SIRT1-7. The NAD+-dependent catalytic core domain of all the family members functions as NAD+-dependent deacetylase (DAC) and/or mono-ADP- ribosyl transferase (Krueger et al., 2015).
The human sirtuin, SIRT1, is the most extensively researched. It has
potential effects on cell processes ranging from cell survival through its substrates to apoptotic signalling. It also deacetylates many other proteins and acts as a regulator of stress reactions involving cellular pathways (Becatti et al., 2014). Due to its increased expression in some forms of cancers and its function in inactivating proteins involved in tumour suppression and DNA damage repair, SIRT1 has been considered a tumour promoter (Su et al., 2020).
The aim of this was to estimate the level of SIRT-1 in the blood of HBV, HCV, and HCC diseased patients and to compare its level between selected group, investigate the possible role of SIRT-1 in the pathogenesis of the disease and determine the role of SIRT-1 as a tumor marker compared to other markers like α- fetoprotein.
The 160 studied subjects were divided into four groups as follows:
- group A: (n = 40) Healthy Control.
- group B: (n = 40) HBV patients.
- group C: (n = 40) HCV patients.
- group D: (n = 40) HCC patients.
All groups were subjected to:
1- History taking; included age, sex, onset, course, duration of illness 2- General examination was done
3- Abdominal examination was done
4- Investigations were done; they included ALT, AST, total, direct bilirubin, albumin, ALP, creatinine, AFP, HBsAG, HCV RNA, HCV antibody and liver biopsy.
5- Serum levels of Sirt-1 was estimated
Results revealed that:
1- There was no significant difference in age between HBV and HCV group as compared to control, while there was significant increase in age in HCC as compared to control. There was no significant difference in age of HCV group as compared to HBV group, whereas, there was significant increase in age of HCC group as compared to HBV group. There was significant increase in age of HCC group as compared to HCV group.
2- There was no significant difference in sex between HBV group and HCV group as compared to the normal control group, while there was significant difference in sex in HCC group as compared to the normal control. There was no significant difference in sex of HCV compared to HBV group, whereas, there was significant difference in HCC compared to HBV group. There was significant difference in sex of HCC compared to HCV group
3- Results of the current study observed that there was significant increase in AST and ALT in HBV, HCV and HCC group as compared to controls. There was significant decrease in AST in HCV as compared to HBV group, whereas there was no significant difference in ALT in HCV as compared to HBV group, and no significant difference in AST and ALT levels between HCC group and HBV group. There was significant increase in AST and ALT in HCC as compared to HCV group.
4- There was no significant difference in total and direct bilirubin in HBV group and HCV group as compared to the normal control group, while there was significant increase in total and direct bilirubin in HCC group as compared to control. ALP was higher in HBV group than the control, and it was lower in HCV group than control group, with no significant difference.
Total, direct bilirubin was higher in HCC than HBV group, while ALP was lower in HCC than HBV group, with no significant difference. Total, direct bilirubin and ALP levels were lower in HCV than HBV group, with no significant difference. There was significant increase in total and direct bilirubin, and ALP in HCC group as compared to HCV group.
5- There was no significant difference in albumin levels in HBV group as compared to the normal control group, while there was significant decrease in albumin in HCV group and HCC group as compared to the normal control. There was no significant difference in albumin of HCV group and HCC group as compared to HBV group. There was significant decrease in albumin in HCC group as compared to HCV.
6- There was no significant difference in creatinine levels in HBV group as compared to the normal control group, while there was significant increase in creatinine levels in HCV group and HCC group as compared to the normal control. There was no significant difference in creatinine levels of HCV group and HCC group as compared to HBV group. There was significant increase in creatinine levels in HCC group as compared to HCV group.
7- HBsAg was negative in all members of the control group and HCV group, while it was positive in all patients of HBV group. In HCC group, 5% of patients were HBsAg positive and 95% of patients were HBsAg negative. HCV-RNA and HCV AB were negative in all members of the control group and HBV group. HCV-RNA and HCV AB were positive in all of the HCV group patients. In HCC group, 95% of patients
were HCV-RNA and HCV AB positive and 5% of patients were HCV-RNA and HCV AB negative.
8- There was no significant difference in AFP levels in HBV group as compared to the normal control group, while there was significant increase in AFP levels in HCV group and HCC group as compared to the normal control. There was significant increase in AFP levels in HCV group and HCC group as compared to HBV group. There was significant increase in AFP in HCC group as compared to HCV group.
9- There was significant increase in SIRT-1 in HBV group, HCV group and HCC group as compared to the normal control. There was significant increase in SIRT-1 in HCV group and HCC as compared to HBV group. There was significant increase in SIRT-1 in HCC group as compared to HCV group.
In conclusion, SIRT-1 may be included in the pathogenesis of HCC, and it may be used as a tumor marker for HCC.