Host Factors in the Natural History of Chronic Hepatitis B: Role of Genetic Determinants
Background. The host immune system plays an important role in hepatitis B virus (HBV) infection manifestation. Genetic polymorphisms of several inflammatory cytokines, including TNF-α and IL-10, have been associated with chronic hepatitis B (CHB) progression, although with contradicting results. CHB...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | International Journal of Hepatology |
| Online Access: | http://dx.doi.org/10.1155/2022/6046677 |
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| author | null Turyadi Billy Witanto Korri E. El-Khobar M. Luthfi Parewangi M. Rezki Rasyak Dhita P. Wibowo Meta D. Thedja Irawan Yusuf Muh. Nasrum Massi Ilhamjaya Patellongi Din Syafruddin David H. Muljono |
| author_facet | null Turyadi Billy Witanto Korri E. El-Khobar M. Luthfi Parewangi M. Rezki Rasyak Dhita P. Wibowo Meta D. Thedja Irawan Yusuf Muh. Nasrum Massi Ilhamjaya Patellongi Din Syafruddin David H. Muljono |
| author_sort | null Turyadi |
| collection | DOAJ |
| description | Background. The host immune system plays an important role in hepatitis B virus (HBV) infection manifestation. Genetic polymorphisms of several inflammatory cytokines, including TNF-α and IL-10, have been associated with chronic hepatitis B (CHB) progression, although with contradicting results. CHB progression can be categorized into four phases, immune tolerance (IT), immune clearance (IC), low/no replicative (LR), and e-negative hepatitis (ENH), with HBeAg seroconversion as an important milestone. Here, we determined the association of TNF-α (rs1800629) and IL-10 (rs1800896 and rs1800872) SNPs in the context of CHB natural history progression, particularly to HBeAg seroconversion, in Indonesian CHB patients. Methods. A total of 287 subjects were recruited and categorized into distinct CHB phases based on HBeAg, viral load, and ALT levels. TNF-α and IL-10 SNPs were determined using PCR-RFLP and confirmed with direct sequencing. The association between SNP genotypes with CHB dynamics was determined using logistic regression presented as odds ratio (OR) with 95% CI. Results. No significant association was found between IL-10 -592A/C polymorphism and progression of IT and IC to LR, IT and IC to ENH, and LR to ENH phases in all the gene models. IL-10 rs1800896 and TNF-α rs1800629 could not be analyzed using logistic regression. Subjects’ age (≥40 years old) was significantly associated with IT and IC to LR (OR: 2.191, 95% CI 1.067–4.578, P=0.034), IT and IC to ENH (OR: 7.460, 95% CI 3.316–18.310, P<0.001), and LR to ENH (OR: 5.252, 95% CI 2.010–14.858, P=0.001). Male gender was associated with LR to ENH (OR: 4.077, 95% CI 1.605–11.023, P=0.004). Conclusions. Age and male gender were associated with CHB phase progression instead of the TNF-α and IL-10 polymorphisms. It would be beneficial to study not only the effect of host determinants but also the viral factor to understand the mechanisms of CHB phase progression. |
| format | Article |
| id | doaj-art-dfe379558f944db7b49e559badd841f7 |
| institution | Kabale University |
| issn | 2090-3456 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Hepatology |
| spelling | doaj-art-dfe379558f944db7b49e559badd841f72025-02-03T01:21:05ZengWileyInternational Journal of Hepatology2090-34562022-01-01202210.1155/2022/6046677Host Factors in the Natural History of Chronic Hepatitis B: Role of Genetic Determinantsnull Turyadi0Billy Witanto1Korri E. El-Khobar2M. Luthfi Parewangi3M. Rezki Rasyak4Dhita P. Wibowo5Meta D. Thedja6Irawan Yusuf7Muh. Nasrum Massi8Ilhamjaya Patellongi9Din Syafruddin10David H. Muljono11Post Graduate SchoolEijkman Center for Molecular BiologyEijkman Center for Molecular BiologyFaculty of MedicineEijkman Center for Molecular BiologyEijkman Center for Molecular BiologyEijkman Center for Molecular BiologyFaculty of MedicineFaculty of MedicineFaculty of MedicineEijkman Center for Molecular BiologyEijkman Center for Molecular BiologyBackground. The host immune system plays an important role in hepatitis B virus (HBV) infection manifestation. Genetic polymorphisms of several inflammatory cytokines, including TNF-α and IL-10, have been associated with chronic hepatitis B (CHB) progression, although with contradicting results. CHB progression can be categorized into four phases, immune tolerance (IT), immune clearance (IC), low/no replicative (LR), and e-negative hepatitis (ENH), with HBeAg seroconversion as an important milestone. Here, we determined the association of TNF-α (rs1800629) and IL-10 (rs1800896 and rs1800872) SNPs in the context of CHB natural history progression, particularly to HBeAg seroconversion, in Indonesian CHB patients. Methods. A total of 287 subjects were recruited and categorized into distinct CHB phases based on HBeAg, viral load, and ALT levels. TNF-α and IL-10 SNPs were determined using PCR-RFLP and confirmed with direct sequencing. The association between SNP genotypes with CHB dynamics was determined using logistic regression presented as odds ratio (OR) with 95% CI. Results. No significant association was found between IL-10 -592A/C polymorphism and progression of IT and IC to LR, IT and IC to ENH, and LR to ENH phases in all the gene models. IL-10 rs1800896 and TNF-α rs1800629 could not be analyzed using logistic regression. Subjects’ age (≥40 years old) was significantly associated with IT and IC to LR (OR: 2.191, 95% CI 1.067–4.578, P=0.034), IT and IC to ENH (OR: 7.460, 95% CI 3.316–18.310, P<0.001), and LR to ENH (OR: 5.252, 95% CI 2.010–14.858, P=0.001). Male gender was associated with LR to ENH (OR: 4.077, 95% CI 1.605–11.023, P=0.004). Conclusions. Age and male gender were associated with CHB phase progression instead of the TNF-α and IL-10 polymorphisms. It would be beneficial to study not only the effect of host determinants but also the viral factor to understand the mechanisms of CHB phase progression.http://dx.doi.org/10.1155/2022/6046677 |
| spellingShingle | null Turyadi Billy Witanto Korri E. El-Khobar M. Luthfi Parewangi M. Rezki Rasyak Dhita P. Wibowo Meta D. Thedja Irawan Yusuf Muh. Nasrum Massi Ilhamjaya Patellongi Din Syafruddin David H. Muljono Host Factors in the Natural History of Chronic Hepatitis B: Role of Genetic Determinants International Journal of Hepatology |
| title | Host Factors in the Natural History of Chronic Hepatitis B: Role of Genetic Determinants |
| title_full | Host Factors in the Natural History of Chronic Hepatitis B: Role of Genetic Determinants |
| title_fullStr | Host Factors in the Natural History of Chronic Hepatitis B: Role of Genetic Determinants |
| title_full_unstemmed | Host Factors in the Natural History of Chronic Hepatitis B: Role of Genetic Determinants |
| title_short | Host Factors in the Natural History of Chronic Hepatitis B: Role of Genetic Determinants |
| title_sort | host factors in the natural history of chronic hepatitis b role of genetic determinants |
| url | http://dx.doi.org/10.1155/2022/6046677 |
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