{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:36:06Z","timestamp":1790026566610,"version":"4.0.1"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T00:00:00Z","timestamp":1596758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Financiadora de Estudos e Projetos (FINEP)","award":["010409605"],"award-info":[{"award-number":["010409605"]}]},{"DOI":"10.13039\/501100006507","name":"Fundacao Oswaldo Cruz","doi-asserted-by":"publisher","award":["Intramural Research Program"],"award-info":[{"award-number":["Intramural Research Program"]}],"id":[{"id":"10.13039\/501100006507","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["research fellowships"],"award-info":[{"award-number":["research fellowships"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006181","name":"Fundac\u0327a\u0303o de Amparo a\u0300 Pesquisa do Estado da Bahia","doi-asserted-by":"publisher","award":["research fellowships"],"award-info":[{"award-number":["research fellowships"]}],"id":[{"id":"10.13039\/501100006181","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Hepatitis B virus (HBV) infection remains a major public health concern. The interaction between HBV and the host inflammatory response is an important contributing factor driving liver damage and diseases outcomes. Here, we performed a retrospective analysis employing an adapted molecular degree of perturbation (MDP) score system to assess the overall inflammatory imbalance related to persistent HBV infection. Plasma levels of several cytokines, chemokines, and other inflammatory markers were measured in Brazilian individuals diagnosed with either chronic HBV or previous HBV infection, as well as in uninfected controls between 2006 and 2007. Multidimensional analyses were used to depict and compare the overall expression profile of inflammatory markers between distinct clinical groups. Chronic HBV patients exhibited a marked inflammatory imbalance, characterized by heightened MDP scores and a distinct profile of correlation networks inputting plasma concentrations of the biomarkers, compared with either individuals with previous HBV or controls. Furthermore, in participants with chronic HBV infection, the viral loads in peripheral blood were directly proportional to overall molecular perturbation as well as to specific perturbations of interleukin (IL)-4 and interferon (IFN)-\u03b3 concentrations. These findings highlight additional nuances about systemic inflammation related to persistent HBV infection.<\/jats:p>","DOI":"10.3390\/v12080864","type":"journal-article","created":{"date-parts":[[2020,8,10]],"date-time":"2020-08-10T05:07:23Z","timestamp":1597036043000},"page":"864","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Chronic Hepatitis B Infection Is Associated with Increased Molecular Degree of Inflammatory Perturbation in Peripheral Blood"],"prefix":"10.3390","volume":"12","author":[{"given":"Caian L.","family":"Vinhaes","sequence":"first","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Salvador 40296-710, Brazil"},{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 41810-710, Brazil"},{"name":"Curso de Medicina, Centro Universit\u00e1rio Faculdade de Tecnologia e Ci\u00eancias (UniFTC), Salvador 41741-590, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00eds A. B.","family":"Cruz","sequence":"additional","affiliation":[{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 41810-710, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo C.","family":"Menezes","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Salvador 40296-710, Brazil"},{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 41810-710, Brazil"},{"name":"Faculdade de Medicina, Universidade Federal da Bahia, Salvador 40110-100, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8458-9315","authenticated-orcid":false,"given":"Thomas A.","family":"Carmo","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Salvador 40296-710, Brazil"},{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 41810-710, Brazil"},{"name":"Curso de Medicina, Universidade Salvador (UNIFACS), Laureate Universities, Salvador 41720-200, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6883-8422","authenticated-orcid":false,"given":"Mar\u00eda B.","family":"Arriaga","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Salvador 40296-710, Brazil"},{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 41810-710, Brazil"},{"name":"Faculdade de Medicina, Universidade Federal da Bahia, Salvador 40110-100, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur T. L.","family":"Queiroz","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Salvador 40296-710, Brazil"},{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 41810-710, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5823-7903","authenticated-orcid":false,"given":"Manoel","family":"Barral-Netto","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Salvador 40296-710, Brazil"},{"name":"Faculdade de Medicina, Universidade Federal da Bahia, Salvador 40110-100, Brazil"},{"name":"Instituto Nacional de Ciencia e Tecnologia de Investiga\u00e7\u00e3o Em Imunologia, S\u00e3o Paulo 05403-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6833-3811","authenticated-orcid":false,"given":"Bruno B.","family":"Andrade","sequence":"additional","affiliation":[{"name":"Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ), Salvador 40296-710, Brazil"},{"name":"Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador 41810-710, Brazil"},{"name":"Curso de Medicina, Centro Universit\u00e1rio Faculdade de Tecnologia e Ci\u00eancias (UniFTC), Salvador 41741-590, Brazil"},{"name":"Faculdade de Medicina, Universidade Federal da Bahia, Salvador 40110-100, Brazil"},{"name":"Curso de Medicina, Universidade Salvador (UNIFACS), Laureate Universities, Salvador 41720-200, Brazil"},{"name":"Escola Bahiana de Medicina e Sa\u00fade P\u00fablica (EBMSP), Salvador 40290-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11630","DOI":"10.3748\/wjg.v20.i33.11630","article-title":"Molecular mechanism of hepatitis B virus-induced hepatocarcinogenesis","volume":"20","author":"Tarocchi","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_2","unstructured":"WHO (2017). Global Hepatitis Report 2017, World Health Organization."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/S0140-6736(17)32152-9","article-title":"Global, regional, and national age-sex specific mortality for 264 causes of death, 1980\u20132016: A systematic analysis for the global burden of disease study 2016","volume":"390","author":"Naghavi","year":"2017","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1056\/NEJMra031087","article-title":"Hepatitis B virus infection\u2014Natural history and clinical consequences","volume":"350","author":"Ganem","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"18035","DOI":"10.1038\/nrdp.2018.35","article-title":"Hepatitis B virus infection","volume":"4","author":"Yuen","year":"2018","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1016\/S0140-6736(14)60220-8","article-title":"Hepatitis B virus infection","volume":"384","author":"Chan","year":"2014","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1053\/j.gastro.2016.07.012","article-title":"HBV DNA integration and clonal hepatocyte expansion in chronic hepatitis B patients considered immune tolerant","volume":"151","author":"Mason","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1136\/gutjnl-2011-301073","article-title":"Innate and adaptive immune responses in chronic hepatitis B virus infections: Towards restoration of immune control of viral infection","volume":"61","author":"Bertoletti","year":"2012","journal-title":"Gut"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.1128\/JVI.02844-06","article-title":"Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection","volume":"81","author":"Boni","year":"2007","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/ni.2035","article-title":"T cell exhaustion","volume":"12","author":"Wherry","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4911","DOI":"10.1128\/JVI.77.8.4911-4927.2003","article-title":"Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment","volume":"77","author":"Wherry","year":"2003","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1002\/hep.23936","article-title":"The immunoregulatory role of CD244 in chronic hepatitis B infection and its inhibitory potential on virus-specific CD8+ T-cell function","volume":"52","author":"Raziorrouh","year":"2010","journal-title":"Hepatology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1038\/nm1492","article-title":"Interleukin-10 determines viral clearance or persistence in vivo","volume":"12","author":"Brooks","year":"2006","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.4049\/jimmunol.1103139","article-title":"IL-10-producing regulatory B cells in the pathogenesis of chronic hepatitis B virus infection","volume":"189","author":"Das","year":"2012","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1136\/gutjnl-2014-308989","article-title":"Serum viral duplex-linear DNA proportion increases with the progression of liver disease in patients infected with HBV","volume":"65","author":"Zhao","year":"2015","journal-title":"Gut"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Vinhaes, C.L., Arriaga, M.B., De Almeida, B.L., Oliveira, J.V., Santos, C.S.I., Calcagno, J., Carvalho, T.X., Giovanetti, M., Alcantara, L.C.J., and De Siqueira, I.C. (2020). Newborns with zika virus-associated microcephaly exhibit marked systemic inflammatory imbalance. J. Infect. Dis.","DOI":"10.1093\/infdis\/jiaa197"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8002","DOI":"10.1038\/s41598-019-44513-8","article-title":"Molecular degree of perturbation of plasma inflammatory markers associated with tuberculosis reveals distinct disease profiles between Indian and Chinese populations","volume":"9","author":"Vinhaes","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11358","DOI":"10.1038\/s41598-020-68255-0","article-title":"Aging increases the systemic molecular degree of inflammatory perturbation in patients with tuberculosis","volume":"10","author":"Vinhaes","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"154759","DOI":"10.1016\/j.cyto.2019.154759","article-title":"Changes in inflammatory protein and lipid mediator profiles persist after antitubercular treatment of pulmonary and extrapulmonary tuberculosis: A prospective cohort study","volume":"123","author":"Vinhaes","year":"2019","journal-title":"Cytokine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1038\/s41598-017-01767-4","article-title":"Systems immunology of diabetes-tuberculosis comorbidity reveals signatures of disease complications","volume":"7","author":"Fukutani","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Barretto, J.R., Boa-Sorte, N., Vinhaes, C.L., Malta-Santos, H., Rebou\u00e7as-Silva, J., Ramos, C.F., Torres-Nascimento, M.A.S., Borges, V.M., and Andrade, B.B. (2020). Heightened plasma levels of transforming growth factor beta (TGF-\u03b2) and increased degree of systemic biochemical perturbation characterizes hepatic steatosis in overweight pediatric patients: A cross-sectional study. Nutrients, 12.","DOI":"10.3390\/nu12061650"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Andrade, B.B., Santos, C.J.N., Camargo, L.M., Souza-Neto, S.M., Reis-Filho, A., Clar\u00eancio, J., Mendon\u00e7a, V.R.R., Luz, N.F., Camargo, E.P., and Barral, A. (2011). Hepatitis B infection is associated with asymptomatic malaria in the brazilian amazon. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019841"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cruz, L.A.B., Netto, M.B., and Andrade, B.B. (2018). Distinct inflammatory profile underlies pathological increases in creatinine levels associated with Plasmodium vivax malaria clinical severity. PLoS Neglected Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006306"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cruz, L.A.B., Moraes, M.O.A., Queiroga-Barros, M.R., Fukutani, K.F., Netto, M.B., and Andrade, B.B. (2019). Chronic hepatitis B virus infection drives changes in systemic immune activation profile in patients coinfected with Plasmodium vivax malaria. PLoS Neglected Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007535"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1475-2875-9-13","article-title":"Severe Plasmodium vivax malaria exhibits marked inflammatory imbalance","volume":"9","author":"Andrade","year":"2010","journal-title":"Malar. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1475-2875-12-69","article-title":"Networking the host immune response in Plasmodium vivax malaria","volume":"12","author":"Queiroz","year":"2013","journal-title":"Malar. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.chom.2012.10.011","article-title":"Metabolic adaptation to tissue iron overload confers tolerance to malaria","volume":"12","author":"Gozzelino","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/1475-2875-9-117","article-title":"Towards a precise test for malaria diagnosis in the Brazilian Amazon: Comparison among field microscopy, a rapid diagnostic test, nested PCR, and a computational expert system based on artificial neural networks","volume":"9","author":"Andrade","year":"2010","journal-title":"Malar. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/1475-2875-8-121","article-title":"Anti-Anopheles darlingi saliva antibodies as marker of Plasmodium vivax infection and clinical immunity in the Brazilian Amazon","volume":"8","author":"Andrade","year":"2009","journal-title":"Malar. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.4049\/jimmunol.0904179","article-title":"Heme impairs prostaglandin E2 and TGF-\u03b2 production by human mononuclear cells via cu\/zn superoxide dismutase: Insight into the pathogenesis of severe malaria","volume":"185","author":"Andrade","year":"2010","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Andrade, B.B., Reis-Filho, A., Souza-Neto, S.M., Raffaele-Netto, I., Camargo, L.M.A., Barral, A., and Netto, M.B. (2010). Plasma superoxide dismutase-1 as a surrogate marker of vivax malaria severity. PLoS Neglected Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000650"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.tube.2007.03.004","article-title":"Interferon\u03b3\/IL10 ratio defines the disease severity in pulmonary and extra pulmonary tuberculosis","volume":"87","author":"Jamil","year":"2007","journal-title":"Tuberculosis"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Xia, Y., and Protzer, U. (2017). Control of hepatitis B virus by cytokines. Viruses, 9.","DOI":"10.3390\/v9010018"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.yexcr.2011.01.005","article-title":"Chemokines in health and disease","volume":"317","author":"Raman","year":"2011","journal-title":"Exp. Cell Res."},{"key":"ref_36","first-page":"121","article-title":"CXCL10\/IP-10 in infectious diseases pathogenesis and potential therapeutic implications","volume":"22","author":"Liu","year":"2011","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.jhep.2016.12.011","article-title":"Functional role of CCL5\/RANTES for HCC progression during chronic liver disease","volume":"66","author":"Mohs","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.4049\/jimmunol.174.3.1549","article-title":"Monocyte chemoattractant protein-1 and ccr2 interactions are required for ifn-\u03b1\/\u03b2-induced inflammatory responses and antiviral defense in liver","volume":"174","author":"Hokeness","year":"2005","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/nri3070","article-title":"Monocyte recruitment during infection and inflammation","volume":"11","author":"Shi","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.jcmgh.2017.07.003","article-title":"Hepatitis B virus activates signal transducer and activator of transcription 3 supporting hepatocyte survival and virus replication","volume":"4","author":"Quasdorff","year":"2017","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4129","DOI":"10.4049\/jimmunol.158.9.4129","article-title":"Differential CC chemokine-induced enhancement of T helper cell cytokine production","volume":"158","author":"Karpus","year":"1997","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"11867","DOI":"10.1038\/s41598-017-11975-7","article-title":"Differential serum cytokine profiles in patients with chronic hepatitis b, c, and hepatocellular carcinoma","volume":"7","author":"Estevez","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nature10599","article-title":"Senescence surveillance of pre-malignant hepatocytes limits liver cancer development","volume":"479","author":"Kang","year":"2011","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"164","DOI":"10.3748\/wjg.v11.i2.164","article-title":"Desensitization of T lymphocyte function by CXCR3 ligands in human hepatocellular carcinoma","volume":"11","author":"Liu","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.jhep.2008.06.009","article-title":"The role of serial measurement of serum HBV DNA levels in patients with chronic HBeAg(\u2212) hepatitis B infection: Association with liver disease progression. A prospective cohort study","volume":"49","author":"Zacharakis","year":"2008","journal-title":"J. Hepatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/S2055-6640(20)30303-4","article-title":"Country of residence is associated with distinct inflammatory biomarker signatures in HIV-infected patients","volume":"3","author":"Manion","year":"2017","journal-title":"J. Virus Erad."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Gu, Y., Lian, Y., Gu, L., Chen, L., Li, X., Zhou, L., Huang, Y., Wang, J., and Huang, Y. (2019). Correlations between cytokines produced by T cells and clinical-virological characteristics in untreated chronic hepatitis B patients. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-3853-2"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S72","DOI":"10.1002\/hep.22884","article-title":"The reveal-HBV study group hepatitis B virus DNA levels and outcomes in chronic hepatitis B","volume":"49","author":"Chen","year":"2009","journal-title":"Hepatology"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/8\/864\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:57:59Z","timestamp":1760176679000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/8\/864"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,7]]},"references-count":48,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["v12080864"],"URL":"https:\/\/doi.org\/10.3390\/v12080864","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,7]]}}}