Insights into the Correlation between Toll-Like Receptor 2 Polymorphism and HBV-Related Disease Progression and Occurrence of Hepatocellular Carcinoma: A Case-Control Study in Egyptian Patients

Background and Aim. Hepatitis B virus (HBV) infection causes a variety of clinical manifestations, including liver cirrhosis and hepatocellular carcinoma (HCC). Toll-like receptors (TLRs) have crucial functions in immune and inflammatory control. Therefore, this study highlights the impact of TLR2 g...

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Main Authors: Naglaa S. Elabd, Marwa L. Helal, Mohsen Elkhayat, Heba Kamal Abd-ElKhalek, Doaa M. Ahmed, Asmaa M. El-Shemy, Yara S. Elsaadawy, Rasha A. Abdelmoneum, Hind S. AboShabaan, Randa M. Seddik
Format: Article
Language:English
Published: Wiley 2024-01-01
Series:Canadian Journal of Infectious Diseases and Medical Microbiology
Online Access:http://dx.doi.org/10.1155/2024/5797895
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author Naglaa S. Elabd
Marwa L. Helal
Mohsen Elkhayat
Heba Kamal Abd-ElKhalek
Doaa M. Ahmed
Asmaa M. El-Shemy
Yara S. Elsaadawy
Rasha A. Abdelmoneum
Hind S. AboShabaan
Randa M. Seddik
author_facet Naglaa S. Elabd
Marwa L. Helal
Mohsen Elkhayat
Heba Kamal Abd-ElKhalek
Doaa M. Ahmed
Asmaa M. El-Shemy
Yara S. Elsaadawy
Rasha A. Abdelmoneum
Hind S. AboShabaan
Randa M. Seddik
author_sort Naglaa S. Elabd
collection DOAJ
description Background and Aim. Hepatitis B virus (HBV) infection causes a variety of clinical manifestations, including liver cirrhosis and hepatocellular carcinoma (HCC). Toll-like receptors (TLRs) have crucial functions in immune and inflammatory control. Therefore, this study highlights the impact of TLR2 gene polymorphism on the progression of HBV-linked liver diseases (liver cirrhosis and HCC). Methods. In total, 170 chronic HBV patients and 50 healthy controls of comparable age and gender were included in this case-control study. Clinical, laboratory, and imaging evaluations were conducted. ELISA was used to determine serum IL-6 levels, and TLR2 (rs3804099) genotyping allelic discrimination assay was performed using real-time PCR. Results. IL-6 values were significantly higher in the HCC group, followed by the cirrhotic group, than those in chronic hepatitis and control groups (p<0.001), with a significant correlation with disease activity and progression parameters. TRL2 homozygous TT was the most frequent in the control group, but the CC genotype was significantly more prevalent in the HCC group than that in the other groups. Furthermore, the CC genetic variant was associated with higher levels of IL-6 and viral load in all HBV patients, whereas the TT genotype was associated with larger tumor size. Multivariate regression analysis demonstrated that in chronic HBV patients, viral load and TRL2 polymorphism are independent risk factors associated with the progression from chronic hepatitis to liver cirrhosis and to HCC. Similarly, the HBV viral load (p=0.03, OR = 2.45, and 95% CI: 1.69–3.65), IL-6 levels (p=0.04, OR = 3.45, and 95% CI: 2.01–6.9), and TRL2 variants (p=0.01, OR = 4.25, and 95% CI: 2.14–13.5) are independent risk factors associated with disease progression from cirrhosis to HCC. Conclusion. In chronic HBV patients, TRL2 polymorphism and higher IL-6 levels were positively correlated with a higher likelihood of HCC and chronic hepatitis B disease activity and progression.
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spelling doaj-art-1d51eb9089af4251b821c203af616b982025-02-03T07:23:36ZengWileyCanadian Journal of Infectious Diseases and Medical Microbiology1918-14932024-01-01202410.1155/2024/5797895Insights into the Correlation between Toll-Like Receptor 2 Polymorphism and HBV-Related Disease Progression and Occurrence of Hepatocellular Carcinoma: A Case-Control Study in Egyptian PatientsNaglaa S. Elabd0Marwa L. Helal1Mohsen Elkhayat2Heba Kamal Abd-ElKhalek3Doaa M. Ahmed4Asmaa M. El-Shemy5Yara S. Elsaadawy6Rasha A. Abdelmoneum7Hind S. AboShabaan8Randa M. Seddik9Department of Tropical MedicineDepartment of Clinical Biochemistry and Molecular DiagnosticsDepartment of Tropical MedicineDepartment of Internal MedicineDepartment of RadiologyDepartment of Clinical PathologyDepartment of Medical Microbiology and ImmunologyDepartment of Clinical Oncology and Nuclear MedicineBiochemistryDepartment of Tropical MedicineBackground and Aim. Hepatitis B virus (HBV) infection causes a variety of clinical manifestations, including liver cirrhosis and hepatocellular carcinoma (HCC). Toll-like receptors (TLRs) have crucial functions in immune and inflammatory control. Therefore, this study highlights the impact of TLR2 gene polymorphism on the progression of HBV-linked liver diseases (liver cirrhosis and HCC). Methods. In total, 170 chronic HBV patients and 50 healthy controls of comparable age and gender were included in this case-control study. Clinical, laboratory, and imaging evaluations were conducted. ELISA was used to determine serum IL-6 levels, and TLR2 (rs3804099) genotyping allelic discrimination assay was performed using real-time PCR. Results. IL-6 values were significantly higher in the HCC group, followed by the cirrhotic group, than those in chronic hepatitis and control groups (p<0.001), with a significant correlation with disease activity and progression parameters. TRL2 homozygous TT was the most frequent in the control group, but the CC genotype was significantly more prevalent in the HCC group than that in the other groups. Furthermore, the CC genetic variant was associated with higher levels of IL-6 and viral load in all HBV patients, whereas the TT genotype was associated with larger tumor size. Multivariate regression analysis demonstrated that in chronic HBV patients, viral load and TRL2 polymorphism are independent risk factors associated with the progression from chronic hepatitis to liver cirrhosis and to HCC. Similarly, the HBV viral load (p=0.03, OR = 2.45, and 95% CI: 1.69–3.65), IL-6 levels (p=0.04, OR = 3.45, and 95% CI: 2.01–6.9), and TRL2 variants (p=0.01, OR = 4.25, and 95% CI: 2.14–13.5) are independent risk factors associated with disease progression from cirrhosis to HCC. Conclusion. In chronic HBV patients, TRL2 polymorphism and higher IL-6 levels were positively correlated with a higher likelihood of HCC and chronic hepatitis B disease activity and progression.http://dx.doi.org/10.1155/2024/5797895
spellingShingle Naglaa S. Elabd
Marwa L. Helal
Mohsen Elkhayat
Heba Kamal Abd-ElKhalek
Doaa M. Ahmed
Asmaa M. El-Shemy
Yara S. Elsaadawy
Rasha A. Abdelmoneum
Hind S. AboShabaan
Randa M. Seddik
Insights into the Correlation between Toll-Like Receptor 2 Polymorphism and HBV-Related Disease Progression and Occurrence of Hepatocellular Carcinoma: A Case-Control Study in Egyptian Patients
Canadian Journal of Infectious Diseases and Medical Microbiology
title Insights into the Correlation between Toll-Like Receptor 2 Polymorphism and HBV-Related Disease Progression and Occurrence of Hepatocellular Carcinoma: A Case-Control Study in Egyptian Patients
title_full Insights into the Correlation between Toll-Like Receptor 2 Polymorphism and HBV-Related Disease Progression and Occurrence of Hepatocellular Carcinoma: A Case-Control Study in Egyptian Patients
title_fullStr Insights into the Correlation between Toll-Like Receptor 2 Polymorphism and HBV-Related Disease Progression and Occurrence of Hepatocellular Carcinoma: A Case-Control Study in Egyptian Patients
title_full_unstemmed Insights into the Correlation between Toll-Like Receptor 2 Polymorphism and HBV-Related Disease Progression and Occurrence of Hepatocellular Carcinoma: A Case-Control Study in Egyptian Patients
title_short Insights into the Correlation between Toll-Like Receptor 2 Polymorphism and HBV-Related Disease Progression and Occurrence of Hepatocellular Carcinoma: A Case-Control Study in Egyptian Patients
title_sort insights into the correlation between toll like receptor 2 polymorphism and hbv related disease progression and occurrence of hepatocellular carcinoma a case control study in egyptian patients
url http://dx.doi.org/10.1155/2024/5797895
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