{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T14:07:41Z","timestamp":1782396461197,"version":"3.54.5"},"reference-count":51,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T00:00:00Z","timestamp":1661212800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Research and Technology\/National Research and Innovation Agency, Indonesia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["International Journal of Hepatology"],"published-print":{"date-parts":[[2022,8,23]]},"abstract":"<jats:p>Background. The host immune system plays an important role in hepatitis B virus (HBV) infection manifestation. Genetic polymorphisms of several inflammatory cytokines, including TNF-\u03b1 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-\u03b1 (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-\u03b1 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-\u03b1 rs1800629 could not be analyzed using logistic regression. Subjects\u2019 age (\u226540 years old) was significantly associated with IT and IC to LR (OR: 2.191, 95% CI 1.067\u20134.578, <jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:mi>P<\/a:mi>\n                        <a:mo>=<\/a:mo>\n                        <a:mn>0.034<\/a:mn>\n                     <\/a:math>\n                  <\/jats:inline-formula>), IT and IC to ENH (OR: 7.460, 95% CI 3.316\u201318.310, <jats:inline-formula>\n                     <c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <c:mi>P<\/c:mi>\n                        <c:mo>&lt;<\/c:mo>\n                        <c:mn>0.001<\/c:mn>\n                     <\/c:math>\n                  <\/jats:inline-formula>), and LR to ENH (OR: 5.252, 95% CI 2.010\u201314.858, <jats:inline-formula>\n                     <e:math xmlns:e=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\">\n                        <e:mi>P<\/e:mi>\n                        <e:mo>=<\/e:mo>\n                        <e:mn>0.001<\/e:mn>\n                     <\/e:math>\n                  <\/jats:inline-formula>). Male gender was associated with LR to ENH (OR: 4.077, 95% CI 1.605\u201311.023, <jats:inline-formula>\n                     <g:math xmlns:g=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\">\n                        <g:mi>P<\/g:mi>\n                        <g:mo>=<\/g:mo>\n                        <g:mn>0.004<\/g:mn>\n                     <\/g:math>\n                  <\/jats:inline-formula>). Conclusions. Age and male gender were associated with CHB phase progression instead of the TNF-\u03b1 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.<\/jats:p>","DOI":"10.1155\/2022\/6046677","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T20:05:08Z","timestamp":1661285108000},"page":"1-10","source":"Crossref","is-referenced-by-count":3,"title":["Host Factors in the Natural History of Chronic Hepatitis B: Role of Genetic Determinants"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1388-4920","authenticated-orcid":true,"family":"Turyadi","sequence":"first","affiliation":[{"name":"Post Graduate School, Faculty of Medicine, Universitas Hasanuddin, Makassar, Indonesia"},{"name":"Eijkman Center for Molecular Biology, National Research and Innovation Agency, Jakarta, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5077-3923","authenticated-orcid":true,"given":"Billy","family":"Witanto","sequence":"additional","affiliation":[{"name":"Eijkman Center for Molecular Biology, National Research and Innovation Agency, Jakarta, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9383-931X","authenticated-orcid":true,"given":"Korri E.","family":"El-Khobar","sequence":"additional","affiliation":[{"name":"Eijkman Center for Molecular Biology, National Research and Innovation Agency, Jakarta, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9257-9344","authenticated-orcid":true,"given":"M. Luthfi","family":"Parewangi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universitas Hasanuddin, Makassar, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4016-4072","authenticated-orcid":true,"given":"M. Rezki","family":"Rasyak","sequence":"additional","affiliation":[{"name":"Eijkman Center for Molecular Biology, National Research and Innovation Agency, Jakarta, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2237-2094","authenticated-orcid":true,"given":"Dhita P.","family":"Wibowo","sequence":"additional","affiliation":[{"name":"Eijkman Center for Molecular Biology, National Research and Innovation Agency, Jakarta, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2948-4905","authenticated-orcid":true,"given":"Meta D.","family":"Thedja","sequence":"additional","affiliation":[{"name":"Eijkman Center for Molecular Biology, National Research and Innovation Agency, Jakarta, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9891-131X","authenticated-orcid":true,"given":"Irawan","family":"Yusuf","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universitas Hasanuddin, Makassar, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3347-6529","authenticated-orcid":true,"given":"Muh. Nasrum","family":"Massi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universitas Hasanuddin, Makassar, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1100-4360","authenticated-orcid":true,"given":"Ilhamjaya","family":"Patellongi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Universitas Hasanuddin, Makassar, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7141-2545","authenticated-orcid":true,"given":"Din","family":"Syafruddin","sequence":"additional","affiliation":[{"name":"Eijkman Center for Molecular Biology, National Research and Innovation Agency, Jakarta, Indonesia"},{"name":"Faculty of Medicine, Universitas Hasanuddin, Makassar, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5542-106X","authenticated-orcid":true,"given":"David H.","family":"Muljono","sequence":"additional","affiliation":[{"name":"Eijkman Center for Molecular Biology, National Research and Innovation Agency, Jakarta, Indonesia"},{"name":"Faculty of Medicine, Universitas Hasanuddin, Makassar, Indonesia"},{"name":"Faculty of Medicine and Health, University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","volume-title":"Hepatitis B","author":"WHO","year":"2021"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00696"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.01.007"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-015-9675-4"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-010-1179-4"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i24.7644"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-013-9438-z"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22898"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.5005\/jp-journals-l0018-1212"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003784"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.12.036"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/493219"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i24.7696"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.5812\/hepatmon.28287v2"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-016-0218-9"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2014.12.011"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2015.02.015"},{"issue":"1","key":"18","first-page":"14","article-title":"Tumor necrosis factor-alpha gene promoter polymorphism in Iranian patients with chronic hepatitis B","volume":"25","author":"M. 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