{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T18:25:22Z","timestamp":1793816722979,"version":"4.6.1"},"reference-count":152,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T00:00:00Z","timestamp":1630972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014717","name":"National Outstanding Youth Science Fund Project of National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014717","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Chronic hepatitis B virus (HBV) infection remains a major health burden worldwide for which there is still no effective curative treatment. Interferon (IFN) consists of a group of cytokines with antiviral activity and immunoregulatory and antitumor effects, that play crucial roles in both innate and adaptive immune responses. IFN-\u03b1 and its pegylated form have been used for over thirty years to treat chronic hepatitis B (CHB) with advantages of finite treatment duration and sustained virologic response, however, the efficacy is limited and side effects are common. Here, we summarize the status and unique advantages of IFN therapy against CHB, review the mechanisms of IFN-\u03b1 action and factors affecting IFN response, and discuss the possible improvement of IFN-based therapy and the rationale of combinations with other antiviral agents in seeking an HBV cure.<\/jats:p>","DOI":"10.3389\/fimmu.2021.733364","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T04:53:55Z","timestamp":1630990435000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":172,"title":["Interferon and Hepatitis B: Current and Future Perspectives"],"prefix":"10.3389","volume":"12","author":[{"given":"Jianyu","family":"Ye","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieliang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.05.013","article-title":"Covalently Closed Circular DNA: The Ultimate Therapeutic Target for Curing Hepatitis B Virus Infections","volume":"75","author":"Martinez","year":"2021","journal-title":"J Hepatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.3795","article-title":"Chronic Hepatitis B Infection A Review","volume":"319","author":"Tang","year":"2018","journal-title":"Jama-J Am Med Assoc"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.01.004","article-title":"Interferons and Viruses: An Evolutionary Arms Race of Molecular Interactions","volume":"36","author":"Hoffmann","year":"2015","journal-title":"Trends Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20970","article-title":"Therapy of Hepatitis B \u2013 Viral Suppression or Eradication","volume":"43","author":"Perrillo","year":"2006","journal-title":"Hepatology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1466","article-title":"A Randomized Controlled Trial of Pegylated Interferon-Alpha2a Plus Adefovir Dipivoxil for Hepatitis B E Antigen-Negative Chronic Hepatitis B","volume":"14","author":"Piccolo","year":"2009","journal-title":"Antivir Ther"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiac.2020.07.005","article-title":"A Randomized Controlled Trial of Pegylated Interferon-Alpha With Tenofovir Disoproxil Fumarate for Hepatitis B E Antigen-Negative Chronic Hepatitis B: A 48-Week Follow-Up Study","volume":"26","author":"Bahardoust","year":"2020","journal-title":"J Infect Chemother"},{"key":"B7","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1053\/j.gastro.2015.09.043","article-title":"Combination of Tenofovir Disoproxil Fumarate and Peginterferon Alpha-2a Increases Loss of Hepatitis B Surface Antigen in Patients With Chronic Hepatitis B","volume":"150","author":"Marcellin","year":"2016","journal-title":"Gastroenterology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.05.044","article-title":"Switching From Entecavir to PegIFN Alfa-2a in Patients With HBeAg-Positive Chronic Hepatitis B: A Randomised Open-Label Trial (OSST Trial)","volume":"61","author":"Ning","year":"2014","journal-title":"J Hepatol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30119-0","article-title":"A Global Scientific Strategy to Cure Hepatitis B","volume":"4","author":"Revill","year":"2019","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"159","DOI":"10.21037\/atm.2017.03.69","article-title":"Alpha-Interferon Treatment in Hepatitis B","volume":"5","author":"Woo","year":"2017","journal-title":"Ann Transl Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29213","article-title":"A Potent Hepatitis B Surface Antigen Response in Subjects With Inactive Hepatitis B Surface Antigen Carrier Treated With Pegylated-Interferon Alpha","volume":"66","author":"Cao","year":"2017","journal-title":"Hepatology"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv547","article-title":"Peginterferon Is Superior to Nucleos(t)ide Analogues for Prevention of Hepatocellular Carcinoma in Chronic Hepatitis B","volume":"213","author":"Liang","year":"2016","journal-title":"J Infect Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21187","article-title":"Interferon-Inducible Expression of APOBEC3 Editing Enzymes in Human Hepatocytes and Inhibition of Hepatitis B Virus Replication","volume":"43","author":"Bonvin","year":"2006","journal-title":"Hepatology"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02510-06","article-title":"Deamination-Independent Inhibition of Hepatitis B Virus Reverse Transcription by APOBEC3G","volume":"81","author":"Nguyen","year":"2007","journal-title":"J Virol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.12.009","article-title":"Interferon-Inducible MX2 Is a Host Restriction Factor of Hepatitis B Virus Replication","volume":"72","author":"Wang","year":"2020","journal-title":"J Hepatol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23011","article-title":"Tripartite Motif-Containing 22 Inhibits the Activity of Hepatitis B Virus Core Promoter, Which is Dependent on Nuclear-Located RING Domain","volume":"50","author":"Gao","year":"2009","journal-title":"Hepatology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e1006296","DOI":"10.1371\/journal.ppat.1006296","article-title":"Interferon-Inducible Ribonuclease ISG20 Inhibits Hepatitis B Virus Replication Through Directly Binding to the Epsilon Stem-Loop Structure of Viral RNA","volume":"13","author":"Liu","year":"2017","journal-title":"PloS Pathog"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e1008338","DOI":"10.1371\/journal.ppat.1008338","article-title":"Interferon-Stimulated Gene 20 (ISG20) Selectively Degrades N6-Methyladenosine Modified Hepatitis B Virus Transcripts","volume":"16","author":"Imam","year":"2020","journal-title":"PloS Pathog"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.6.2684-2691.2001","article-title":"Inhibition of Hepatitis B Virus Replication by the Interferon-Inducible MxA Protein","volume":"75","author":"Gordien","year":"2001","journal-title":"J Virol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.01.034","article-title":"Hepatitis B Virus Does Not Interfere With Innate Immune Responses in the Human Liver","volume":"154","author":"Suslov","year":"2018","journal-title":"Gastroenterology"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29348","article-title":"Hepatitis B Virus Evades Innate Immunity of Hepatocytes But Activates Cytokine Production by Macrophages","volume":"66","author":"Cheng","year":"2017","journal-title":"Hepatology"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.05.022","article-title":"Control of cccDNA Function in Hepatitis B Virus Infection","volume":"51","author":"Levrero","year":"2009","journal-title":"J Hepatol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.01.001","article-title":"Hepatitis B Virus Replication is Regulated by the Acetylation Status of Hepatitis B Virus cccDNA-Bound H3 and H4 Histones","volume":"130","author":"Pollicino","year":"2006","journal-title":"Gastroenterology"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-020-00928-z","article-title":"IFN-Alpha Confers Epigenetic Regulation of HBV cccDNA Minichromosome by Modulating GCN5-Mediated Succinylation of Histone H3K79 to Clear HBV cccDNA","volume":"12","author":"Yuan","year":"2020","journal-title":"Clin Epigenet"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.6.3350-3357.1995","article-title":"The Covalently Closed Duplex Form of the Hepadnavirus Genome Exists In-Situ as a Heterogeneous Population of Viral Minichromosomes","volume":"69","author":"Newbold","year":"1995","journal-title":"J Virol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1002\/hep.29133","article-title":"PRMT5 Restricts Hepatitis B Virus Replication Through Epigenetic Repression of Covalently Closed Circular DNA Transcription and Interference With Pregenomic RNA Encapsidation","volume":"66","author":"Zhang","year":"2017","journal-title":"Hepatology"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30897","article-title":"Nuclear Sensor Interferon-Inducible Protein 16 Inhibits the Function of Hepatitis B Virus Covalently Closed Circular DNA by Integrating Innate Immune Activation and Epigenetic Suppression","volume":"71","author":"Yang","year":"2020","journal-title":"Hepatology"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0908365106","article-title":"Nuclear HBx Binds the HBV Minichromosome and Modifies the Epigenetic Regulation of cccDNA Function","volume":"106","author":"Belloni","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58847","article-title":"IFN-Alpha Inhibits HBV Transcription and Replication in Cell Culture and in Humanized Mice by Targeting the Epigenetic Regulation of the Nuclear cccDNA Minichromosome","volume":"122","author":"Belloni","year":"2012","journal-title":"J Clin Invest"},{"key":"B30","doi-asserted-by":"publisher","first-page":"e1003613","DOI":"10.1371\/journal.ppat.1003613","article-title":"Alpha-Interferon Suppresses Hepadnavirus Transcription by Altering Epigenetic Modification of cccDNA Minichromosomes","volume":"9","author":"Liu","year":"2013","journal-title":"PloS Pathog"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1126\/science.1243462","article-title":"Specific and Nonhepatotoxic Degradation of Nuclear Hepatitis B Virus cccDNA","volume":"343","author":"Lucifora","year":"2014","journal-title":"Science"},{"key":"B32","doi-asserted-by":"publisher","first-page":"e49568","DOI":"10.15252\/embr.201949568","article-title":"Interferon-Induced Degradation of the Persistent Hepatitis B Virus cccDNA Form Depends on ISG20","volume":"22","author":"Stadler","year":"2021","journal-title":"EMBO Rep"},{"key":"B33","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1053\/j.gastro.2015.09.026","article-title":"Interferon-Gamma and Tumor Necrosis Factor-Alpha Produced by T Cells Reduce the HBV Persistence Form, cccDNA, Without Cytolysis","volume":"150","author":"Xia","year":"2016","journal-title":"Gastroenterology"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nature17170","article-title":"Hepatitis B Virus X Protein Identifies the Smc5\/6 Complex as a Host Restriction Factor","volume":"531","author":"Decorsiere","year":"2016","journal-title":"Nature"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.08.026","article-title":"Hepatitis B Virus X Protein Promotes Degradation of SMC5\/6 to Enhance HBV Replication","volume":"16","author":"Murphy","year":"2016","journal-title":"Cell Rep"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-322571","article-title":"Therapeutic Shutdown of HBV Transcripts Promotes Reappearance of the SMC5\/6 Complex and Silencing of the Viral Genome In Vivo","author":"Allweiss","year":"2021","journal-title":"Gut"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s10059-011-1059-6","article-title":"PKR-Dependent Mechanisms of Interferon-Alpha for Inhibiting Hepatitis B Virus Replication","volume":"32","author":"Park","year":"2011","journal-title":"Mol Cells"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00933-15","article-title":"The Interferon-Inducible Protein Tetherin Inhibits Hepatitis B Virus Virion Secretion","volume":"89","author":"Yan","year":"2015","journal-title":"J Virol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/ni.2647","article-title":"Exosomes Mediate the Cell-to-Cell Transmission of IFN-Alpha-Induced Antiviral Activity","volume":"14","author":"Li","year":"2013","journal-title":"Nat Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa399","article-title":"Interferon-Induced Macrophage-Derived Exosomes Mediate Antiviral Activity Against Hepatitis B Virus Through miR-574-5p","volume":"223","author":"Wu","year":"2021","journal-title":"J Infect Dis"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M116.063503","article-title":"Label-free Proteomic Analysis of Exosomes Derived from Inducible Hepatitis B Virus-Replicating HepAD38 Cell Line","volume":"16","author":"Jia","year":"2017","journal-title":"Mol Cell Proteomics"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01578-18","article-title":"Exosomes Exploit the Virus Entry Machinery and Pathway To Transmit Alpha Interferon-Induced Antiviral Activity","volume":"92","author":"Yao","year":"2018","journal-title":"J Virol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-1114","article-title":"Direct Effects of Type I Interferons on Cells of the Immune System","volume":"17","author":"Hervas-Stubbs","year":"2011","journal-title":"Clin Cancer Res"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-10-183301","article-title":"Dynamic Accumulation of Plasmacytoid Dendritic Cells in Lymph Nodes is Regulated by Interferon-Beta","volume":"114","author":"Gao","year":"2009","journal-title":"Blood"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.12.036","article-title":"Hepatic Immune Regulation and Its Involvement in Viral Hepatitis Infection","volume":"146","author":"Knolle","year":"2014","journal-title":"Gastroenterology"},{"key":"B46","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1146\/annurev.immunol.19.1.65","article-title":"Noncytolytic Control of Viral Infections by the Innate and Adaptive Immune Response","volume":"19","author":"Guidotti","year":"2001","journal-title":"Annu Rev Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.9.3764","article-title":"Cytotoxic T-Lymphocytes Inhibit Hepatitis-B Virus Gene-Expression By a Noncytolytic Mechanism In Transgenic Mice","volume":"91","author":"Guidotti","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.5.2255-2264.2000","article-title":"Relative Sensitivity of Hepatitis B Virus and Other Hepatotropic Viruses to the Antiviral Effects of Cytokines","volume":"74","author":"McClary","year":"2000","journal-title":"J\u00a0Virol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5415.825","article-title":"Viral Clearance Without Destruction of Infected Cells During Acute HBV Infection","volume":"284","author":"Guidotti","year":"1999","journal-title":"Science"},{"key":"B50","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1073\/pnas.0913498107","article-title":"Immune Effectors Required for Hepatitis B Virus Clearance","volume":"107","author":"Yang","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3390\/v9010018","article-title":"Control of Hepatitis B Virus by Cytokines","volume":"9","author":"Xia","year":"2017","journal-title":"Viruses"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.10.021","article-title":"Immune Cell Responses Are Not Required to Induce Substantial Hepatitis B Virus Antigen Decline During Pegylated Interferon-Alpha Administration","volume":"60","author":"Allweiss","year":"2014","journal-title":"J Hepatol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.12.032","article-title":"Peginterferon-Alpha Does Not Improve Early Peripheral Blood HBV-Specific T-Cell Responses in HBeAg-Negative Chronic Hepatitis","volume":"56","author":"Penna","year":"2012","journal-title":"J Hepatol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.09.029","article-title":"Differential Boosting of Innate and Adaptive Antiviral Responses During Pegylated-Interferon-Alpha Therapy of Chronic Hepatitis B","volume":"58","author":"Micco","year":"2013","journal-title":"J Hepatol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29609","article-title":"Hepatitis B Virus Sensitivity to Interferon-Alpha in Hepatocytes is More Associated With Cellular Interferon Response Than With Viral Genotype","volume":"67","author":"Shen","year":"2018","journal-title":"Hepatology"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(05)81483-7","article-title":"Effect of Genotype and Other Baseline Factors on Response to Peginterferon Alpha-2a (40 kDa) (PEGASYS (R)) in HBeAg-POSITIVE Chronic Hepatitis B: Results From a Large, Randomised Study","volume":"42","author":"Cooksley","year":"2005","journal-title":"J Hepatol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043470","article-title":"Peginterferon Alfa-2a, Lamivudine, and the Combination for HBeAg-Positive Chronic Hepatitis B","volume":"352","author":"Lau","year":"2005","journal-title":"New Engl J Med"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)17701-0","article-title":"Pegylated Interferon Alfa-2b Alone or in Combination With Lamivudine for HBeAg-Positive Chronic Hepatitis B: A Randomised","volume":"365","author":"Janssen","year":"2005","journal-title":"Lancet"},{"key":"B59","article-title":"HBV Genotype B is Associated With Better Response to Interferon Therapy in HBeAg(+) Chronic Hepatitis Than Genotype C","volume":"36","author":"Wai","year":"2002","journal-title":"Hepatology"},{"key":"B60","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1002\/hep.25636","article-title":"Presence of Precore and Core Promoter Mutants Limits the Probability of Response to Peginterferon in Hepatitis B E Antigen-Positive Chronic Hepatitis B","volume":"56","author":"Sonneveld","year":"2012","journal-title":"Hepatology"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201625","article-title":"Hepatitis B Virus Surface Antigen Selectively Inhibits TLR2 Ligand-Induced IL-12 Production in Monocytes\/Macrophages by Interfering With JNK Activation","volume":"190","author":"Wang","year":"2013","journal-title":"J Immunol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2009.04.031","article-title":"HBsAg Inhibits TLR9-Mediated Activation and IFN-Alpha Production in Plasmacytoid Dendritic Cells","volume":"46","author":"Xu","year":"2009","journal-title":"Mol Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.04.013","article-title":"Hepatitis B Surface Antigen Seroclearance: Immune Mechanisms, Clinical Impact, Importance for Drug Development","volume":"73","author":"Tout","year":"2020","journal-title":"J Hepatol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"e1000986","DOI":"10.1371\/journal.ppat.1000986","article-title":"Hepatitis B Virus Polymerase Blocks Pattern Recognition Receptor Signaling via Interaction With DDX3: Implications for Immune Evasion","volume":"6","author":"Wang","year":"2010","journal-title":"PloS Pathog"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02760-14","article-title":"Hepatitis B Virus Polymerase Disrupts K63-Linked Ubiquitination of STING to Block Innate Cytosolic DNA-Sensing Pathways","volume":"89","author":"Liu","year":"2015","journal-title":"J Virol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.020552-0","article-title":"Hepatitis B Virus Polymerase Inhibits RIG-I- and Toll-Like Receptor 3-Mediated Beta Interferon Induction in Human Hepatocytes Through Interference With Interferon Regulatory Factor 3 Activation and Dampening of the Interaction Between TBK1\/IKKepsilon and DDX3","volume":"91","author":"Yu","year":"2010","journal-title":"J Gen Virol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01825-10","article-title":"Hepatitis B Virus Regulatory HBx Protein Binds to Adaptor Protein IPS-1 and Inhibits the Activation of Beta Interferon","volume":"85","author":"Kumar","year":"2011","journal-title":"J Virol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903874","article-title":"The Hepatitis B Virus X Protein Disrupts Innate Immunity by Downregulating Mitochondrial Antiviral Signaling Protein","volume":"185","author":"Wei","year":"2010","journal-title":"J Immunol"},{"key":"B69","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.virol.2019.10.009","article-title":"Residues Asn118 and Glu119 of Hepatitis B Virus X Protein Are Critical for HBx-Mediated Inhibition of RIG-I-MAVS Signaling","volume":"539","author":"Wang","year":"2020","journal-title":"Virology"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.18966-0","article-title":"Hepatitis B Virus Downregulates the Human Interferon-Inducible MxA Promoter Through Direct Interaction of Precore\/Core Proteins","volume":"84","author":"Fernandez","year":"2003","journal-title":"J Gen Virol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.3390\/v11050427","article-title":"Human Hepatitis B Virus Core Protein Inhibits IFNalpha-Induced IFITM1 Expression by Interacting With BAF200","volume":"11","author":"Li","year":"2019","journal-title":"Viruses"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.12.042","article-title":"The Hepatitis B E Antigen (HBeAg) Targets and Suppresses Activation of the Toll-Like Receptor Signaling Pathway","volume":"55","author":"Lang","year":"2011","journal-title":"J Hepatol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21482","article-title":"Regulation of Toll-Like Receptor-2 Expression in Chronic Hepatitis B by the Precore Protein","volume":"45","author":"Visvanathan","year":"2007","journal-title":"Hepatology"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00196-19","article-title":"Hepatitis B Virus Precore Protein P22 Inhibits Alpha Interferon Signaling by Blocking STAT Nuclear Translocation","volume":"93","author":"Mitra","year":"2019","journal-title":"J Virol"},{"key":"B75","doi-asserted-by":"publisher","first-page":"16459","DOI":"10.1038\/srep16459","article-title":"Hepatitis B Virus Spliced Variants Are Associated With an Impaired Response to Interferon Therapy","volume":"5","author":"Chen","year":"2015","journal-title":"Sci Rep"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.021","article-title":"Electronic Address Eee, European Association for the Study of the L. EASL 2017 Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection","volume":"67","year":"2017","journal-title":"J Hepatol"},{"key":"B77","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1136\/gut.2005.089722","article-title":"Predicting Response to Peginterferon Alpha-2a, Lamivudine and the Two Combined for HBeAg-Negative Chronic Hepatitis B","volume":"56","author":"Bonino","year":"2007","journal-title":"Gut"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2008.07.013","article-title":"Treatment Predictors of a Sustained Virologic Response in Hepatitis B and C","volume":"49","author":"Kau","year":"2008","journal-title":"J Hepatol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25749","article-title":"IL28B Polymorphisms Predict Interferon-Related Hepatitis B Surface Antigen Seroclearance in Genotype D Hepatitis B E Antigen-Negative Patients With Chronic Hepatitis B","volume":"57","author":"Lampertico","year":"2013","journal-title":"Hepatology"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-016-2283-3","article-title":"Association of STAT4 Polymorphisms With Hepatitis B Virus Infection and Clearance in Chinese Han Population","volume":"48","author":"Jiang","year":"2016","journal-title":"Amino Acids"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28423","article-title":"Genetic Variation in STAT4 Predicts Response to Interferon-Alpha Therapy for Hepatitis B E Antigen-Positive Chronic Hepatitis B","volume":"63","author":"Jiang","year":"2016","journal-title":"Hepatology"},{"key":"B82","doi-asserted-by":"publisher","first-page":"e111677","DOI":"10.1371\/journal.pone.0111677","article-title":"Association of HLA-DP\/DQ and STAT4 Polymorphisms With HBV Infection Outcomes and a Mini Meta-Analysis","volume":"9","author":"Liao","year":"2014","journal-title":"PloS One"},{"key":"B83","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1159\/000342526","article-title":"Polymorphisms Near Interleukin 28b Gene Are Not Associated With Hepatitis B Virus Clearance, Hepatitis B E Antigen Clearance and Hepatocellular Carcinoma Occurrence","volume":"56","author":"Lee","year":"2013","journal-title":"Intervirology"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1841","article-title":"Effect of Host and Viral Factors on Hepatitis B E Antigen-Positive Chronic Hepatitis B Patients Receiving Pegylated Interferon-Alpha-2a Therapy","volume":"16","author":"Tseng","year":"2011","journal-title":"Antiviral Ther"},{"key":"B85","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1053\/j.gastro.2011.11.025","article-title":"Polymorphisms Near IL28B and Serologic Response to Peginterferon in HBeAg-Positive Patients With Chronic Hepatitis B","volume":"142","author":"Sonneveld","year":"2012","journal-title":"Gastroenterology"},{"key":"B86","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.antiviral.2011.12.009","article-title":"Evaluation of Susceptibility Locus for Response to Interferon-Alpha Based Therapy in Chronic Hepatitis B Patients in Chinese","volume":"93","author":"Wu","year":"2012","journal-title":"Antiviral Res"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30497","article-title":"A Functional Variant in Ubiquitin Conjugating Enzyme E2 L3 Contributes to Hepatitis B Virus Infection and Maintains Covalently Closed Circular DNA Stability by Inducing Degradation of Apolipoprotein B mRNA Editing Enzyme Catalytic Subunit 3a","volume":"69","author":"Zhou","year":"2019","journal-title":"Hepatology"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(89)90034-2","article-title":"Interferon Antibodies In Patients With Chronic HBV Infection Treated With Recombinant Interferon","volume":"8","author":"Porres","year":"1989","journal-title":"J\u00a0Hepatol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840120603","article-title":"Interferon Antibodies May Negate The Antiviral Effects Of Recombinant Alpha-Interferon Treatment In Patients With Chronic Hepatitis-B Virus-Infection","volume":"12","author":"Lok","year":"1990","journal-title":"Hepatology"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1136\/gut.30.8.1116","article-title":"Randomized Controlled Trial Of Interferon-Alfa-2a (RBE) (ROFERON-A) For The Treatment Of Chronic Hepatitis-B Virus (HBV) Infection - Factors That Influence Response","volume":"30","author":"Brook","year":"1989","journal-title":"Gut"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2711","article-title":"Presence of Anti-Interferon Antibodies is Not Associated With Non-Response to Pegylated Interferon Treatment in Chronic Hepatitis B","volume":"19","author":"Arends","year":"2014","journal-title":"Antivir Ther"},{"key":"B92","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/j.jhep.2016.12.024","article-title":"Intrahepatic Innate Immune Response Pathways Are Downregulated in Untreated Chronic Hepatitis B","volume":"66","author":"Lebosse","year":"2017","journal-title":"J Hepatol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23361","article-title":"Innate Response to Hepatitis B Virus Infection: Observations Challenging the Concept of a Stealth Virus","volume":"50","author":"Durantel","year":"2009","journal-title":"Hepatology"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.01.044","article-title":"HBV Bypasses the Innate Immune Response and Does Not Protect HCV From Antiviral Activity of Interferon","volume":"154","author":"Mutz","year":"2018","journal-title":"Gastroenterology"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31112","article-title":"Hepatitis B Virus Particles Activate Toll-Like Receptor 2 Signaling Initially Upon Infection of Primary Human Hepatocytes","volume":"72","author":"Zhang","year":"2020","journal-title":"Hepatology"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30054","article-title":"Hepatitis B Virus Evasion From Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase Sensing in Human Hepatocytes","volume":"68","author":"Verrier","year":"2018","journal-title":"Hepatology"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.12.016","article-title":"The RNA Sensor RIG-I Dually Functions as an Innate Sensor and Direct Antiviral Factor for Hepatitis B Virus","volume":"42","author":"Sato","year":"2015","journal-title":"Immunity"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.07.014","article-title":"Early Inhibition of Hepatocyte Innate Responses by Hepatitis B Virus","volume":"63","author":"Luangsay","year":"2015","journal-title":"J\u00a0Hepatol"},{"key":"B99","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1038\/s41467-020-20316-8","article-title":"Hepatitis B Virus Rigs the Cellular Metabolome to Avoid Innate Immune Recognition","volume":"12","author":"Zhou","year":"2021","journal-title":"Nat Commun"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-312742","article-title":"Suppression of Interferon-Mediated Anti-HBV Response by Single CpG Methylation in the 5\u2019-UTR of TRIM22","volume":"67","author":"Lim","year":"2018","journal-title":"Gut"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501362","article-title":"Polarization of Monocytic Myeloid-Derived Suppressor Cells by Hepatitis B Surface Antigen Is Mediated via ERK\/IL-6\/STAT3 Signaling Feedback and Restrains the Activation of T Cells in Chronic Hepatitis B Virus Infection","volume":"195","author":"Fang","year":"2015","journal-title":"J Immunol"},{"key":"B102","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1053\/j.gastro.2012.07.014","article-title":"Restored Function of HBV-Specific T Cells After Long-Term Effective Therapy With Nucleos(T)Ide Analogues","volume":"143","author":"Boni","year":"2012","journal-title":"Gastroenterology"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.11.5535-5545.2004","article-title":"Memory CD8 T-Cell Differentiation During Viral Infection","volume":"78","author":"Wherry","year":"2004","journal-title":"J Virol"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01099-18","article-title":"Type I Interferon Signaling Prevents Hepatitis B Virus-Specific T Cell Responses by Reducing Antigen Expression","volume":"92","author":"Kawashima","year":"2018","journal-title":"J Virol"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1172\/JCI135616","article-title":"Diminished Hepatic IFN Response Following HCV Clearance Triggers HBV Reactivation in Coinfection","volume":"130","author":"Cheng","year":"2020","journal-title":"J Clin Invest"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03553-13","article-title":"Limited Hepatitis B Virus Replication Space in the Chronically Hepatitis C Virus-Infected Liver","volume":"88","author":"Wieland","year":"2014","journal-title":"J Virol"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2010.06541.x","article-title":"The Clinical Implications of Hepatitis B Virus Genotype: Recent Advances","volume":"26","author":"Lin","year":"2011","journal-title":"J Gastroenterol Hepatol"},{"key":"B108","doi-asserted-by":"publisher","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 Primers"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2014.06.028","article-title":"Characteristics of Adults in the Hepatitis B Research Network in North America Reflect Their Country of Origin and Hepatitis B Virus Genotype","volume":"13","author":"Ghany","year":"2015","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B110","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.jcv.2007.03.005","article-title":"Hepatitis B Virus (HBV) Genotypes\/Subgenotypes in China: Mutations in Core Promoter and Precore\/Core and Their Clinical Implications","volume":"39","author":"Yuan","year":"2007","journal-title":"J Clin Virol"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29800","article-title":"Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance","volume":"67","author":"Terrault","year":"2018","journal-title":"Hepatology"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.07.058","article-title":"Insights From Deep Sequencing of the HBV Genome-Unique, Tiny, and Misunderstood","volume":"156","author":"McNaughton","year":"2019","journal-title":"Gastroenterology"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1007\/s11262-019-01689-5","article-title":"Next Generation Sequencing Identifies Baseline Viral Mutants Associated With Treatment Response to Pegylated Interferon in HBeAg-Positive Chronic Hepatitis B","volume":"55","author":"Chuaypen","year":"2019","journal-title":"Virus Genes"},{"key":"B114","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1126\/science.aau7307","article-title":"Long-Term Functional Maintenance of Primary Human Hepatocytes In Vitro","volume":"364","author":"Xiang","year":"2019","journal-title":"Science"},{"key":"B115","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1038\/s41422-018-0103-x","article-title":"Expansion and Differentiation of Human Hepatocyte-Derived Liver Progenitor-Like Cells and Their Use for the Study of Hepatotropic Pathogens","volume":"29","author":"Fu","year":"2019","journal-title":"Cell Res"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1177\/1535370216657448","article-title":"Cell Sources for In Vitro Human Liver Cell Culture Models","volume":"241","author":"Zeilinger","year":"2016","journal-title":"Exp Biol Med (Maywood)"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1412631111","article-title":"Modeling Host Interactions With Hepatitis B Virus Using Primary and Induced Pluripotent Stem Cell-Derived Hepatocellular Systems","volume":"111","author":"Shlomai","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12768","article-title":"An Intrahepatic Transcriptional Signature of Enhanced Immune Activity Predicts Response to Peginterferon in Chronic Hepatitis B","volume":"35","author":"Jansen","year":"2015","journal-title":"Liver Int"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1038\/srep31349","article-title":"Liver Gene Expression Profiles Correlate With Virus Infection and Response to Interferon Therapy in Chronic Hepatitis B Patients","volume":"6","author":"Wu","year":"2016","journal-title":"Sci Rep"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040431","article-title":"Peginterferon Alfa-2a Alone, Lamivudine Alone, and the Two in Combination in Patients With HBeAg-Negative Chronic Hepatitis B","volume":"351","author":"Marcellin","year":"2004","journal-title":"N\u00a0Engl J Med"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2013.09.020","article-title":"Add-On Peg-Interferon Leads to Loss of HBsAg in Patients With HBeAg-Negative Chronic Hepatitis and HBV DNA Fully Suppressed by Long-Term Nucleotide Analogs","volume":"58","author":"Ouzan","year":"2013","journal-title":"J\u00a0Clin Virol"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00249-15","article-title":"Sequential Combination Therapy With Pegylated Interferon Leads to Loss of Hepatitis B Surface Antigen and Hepatitis B E Antigen (HBeAg) Seroconversion in HBeAg-Positive Chronic Hepatitis B Patients Receiving Long-Term Entecavir Treatment","volume":"59","author":"Li","year":"2015","journal-title":"Antimicrob Agents Chemother"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-308546","article-title":"Baseline Quantitative Hepatitis B Core Antibody Titre Alone Strongly Predicts HBeAg Seroconversion Across Chronic Hepatitis B Patients Treated With Peginterferon or Nucleos(T)Ide Analogues","volume":"65","author":"Fan","year":"2016","journal-title":"Gut"},{"key":"B124","doi-asserted-by":"publisher","first-page":"15658","DOI":"10.1038\/s41598-017-15594-0","article-title":"Circulating miR-210 and miR-22 Combined With ALT Predict the Virological Response to Interferon-Alpha Therapy of CHB Patients","volume":"7","author":"Li","year":"2017","journal-title":"Sci Rep"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy270","article-title":"Serum HBV RNA as a Predictor of Peginterferon Alfa-2a Response in Patients With HBeAg-Positive Chronic Hepatitis B","volume":"218","author":"van Bommel","year":"2018","journal-title":"J Infect Dis"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa013","article-title":"Hepatitis B Virus RNA as Early Predictor for Response to Pegylated Interferon Alpha in HBeAg-Negative Chronic Hepatitis B","volume":"72","author":"Farag","year":"2021","journal-title":"Clin Infect Dis"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13046","article-title":"Serum Hepatitis B Core-Related Antigen as a Treatment Predictor of Pegylated Interferon in Patients With HBeAg-Positive Chronic Hepatitis B","volume":"36","author":"Chuaypen","year":"2016","journal-title":"Liver Int"},{"key":"B128","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41586-019-0988-7","article-title":"Structure of the IFNgamma Receptor Complex Guides Design of Biased Agonists","volume":"567","author":"Mendoza","year":"2019","journal-title":"Nature"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032713-120211","article-title":"Insights Into Cytokine-Receptor Interactions From Cytokine Engineering","volume":"33","author":"Spangler","year":"2015","journal-title":"Annu Rev Immunol"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200012073432302","article-title":"Peginterferon Alfa-2a in Patients With Chronic Hepatitis C and Cirrhosis","volume":"343","author":"Heathcote","year":"2000","journal-title":"New Engl J Med"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201503440","article-title":"Enhancing Pharmacokinetics, Tumor Accumulation, and Antitumor Efficacy by Elastin-Like Polypeptide Fusion of Interferon Alpha","volume":"27","author":"Hu","year":"2015","journal-title":"Adv Mater"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2018.11.003","article-title":"PASylated Interferon Alpha Efficiently Suppresses Hepatitis B Virus and Induces Anti-HBs Seroconversion in HBV-Transgenic Mice","volume":"161","author":"Xia","year":"2019","journal-title":"Antiviral Res"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24306","article-title":"Anchoring Interferon Alpha to Apolipoprotein A-I Reduces Hematological Toxicity While Enhancing Immunostimulatory Properties","volume":"53","author":"Fioravanti","year":"2011","journal-title":"Hepatology"},{"key":"B134","doi-asserted-by":"publisher","first-page":"e0216139","DOI":"10.1371\/journal.pone.0216139","article-title":"An Interferon-Like Small Chemical Compound CDM-3008 Suppresses Hepatitis B Virus Through Induction of Interferon-Stimulated Genes","volume":"14","author":"Furutani","year":"2019","journal-title":"PloS One"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610115200","article-title":"An Interferon Alpha2 Mutant Optimized by Phage Display for IFNAR1 Binding Confers Specifically Enhanced Antitumor Activities","volume":"282","author":"Kalie","year":"2007","journal-title":"J Biol Chem"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609001104","article-title":"Directed Evolution of Gene-Shuffled IFN-Alpha Molecules With Activity Profiles Tailored for Treatment of Chronic Viral Diseases","volume":"104","author":"Brideau-Andersen","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"B137","article-title":"In Vitro and In Vivo Characterization of R7025, a Novel Pegylated Human Interferon Alpha Molecule, Generated by DNA Shuffling for the Treatment of Chronic Hepatitis C","volume":"46","author":"Symons","year":"2007","journal-title":"Hepatology"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2009.92","article-title":"New and Experimental Therapies for HCV","volume":"6","author":"Pereira","year":"2009","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.01.002","article-title":"The Molecular Basis for Functional Plasticity in Type I Interferon Signaling","volume":"36","author":"Schreiber","year":"2015","journal-title":"Trends Immunol"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.07.019","article-title":"Binding and Activity of All Human Alpha Interferon Subtypes","volume":"56","author":"Lavoie","year":"2011","journal-title":"Cytokine"},{"key":"B141","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1002\/hep.31282","article-title":"Functional Comparison of IFN-Alpha Subtypes Reveals Potent HBV Suppression by a Concerted Action of IFN-Alpha and -Gamma Signaling","volume":"73","author":"Chen","year":"2021","journal-title":"Hepatology"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.3390\/v13061090","article-title":"Review of Lambda Interferons in Hepatitis B Virus Infection: Outcomes and Therapeutic Strategies","volume":"13","author":"Novotny","year":"2021","journal-title":"Viruses"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1038\/ni873","article-title":"IL-28, IL-29 and Their Class II Cytokine Receptor IL-28r","volume":"4","author":"Sheppard","year":"2003","journal-title":"Nat Immunol"},{"key":"B144","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1002\/hep.21312","article-title":"Interleukin-29 Uses a Type 1 Interferon-Like Program to Promote Antiviral Responses in Human Hepatocytes","volume":"44","author":"Doyle","year":"2006","journal-title":"Hepatology"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0182-z","article-title":"Interferon-Lambda Orchestrates Innate and Adaptive Mucosal Immune Responses","volume":"19","author":"Ye","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"B146","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/nature08309","article-title":"Genetic Variation in IL28B Predicts Hepatitis C Treatment-Induced Viral Clearance","volume":"461","author":"Ge","year":"2009","journal-title":"Nature"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit121","article-title":"HLA-DP and IL28B Polymorphisms: Influence of Host Genome on Hepatitis B Surface Antigen Seroclearance in Chronic Hepatitis B","volume":"56","author":"Seto","year":"2013","journal-title":"Clin Infect Dis"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12595","article-title":"Interleukin-28 Gene Polymorphisms may Contribute to HBsAg Persistence and the Development of HBeAg-Negative Chronic Hepatitis B","volume":"35","author":"Karatayli","year":"2015","journal-title":"Liver Int"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.12.018","article-title":"Peginterferon Lambda for the Treatment of HBeAg-Positive Chronic Hepatitis B: A Randomized Phase 2b Study (LIRA-B)","volume":"64","author":"Chan","year":"2016","journal-title":"J Hepatol"},{"key":"B150","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1146\/annurev-med-080119-103356","article-title":"New Therapeutics for Hepatitis B: The Road to Cure","volume":"72","author":"Naggie","year":"2021","journal-title":"Annu Rev Med"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.10.017","article-title":"Efficacy of NVR 3-778, Alone and In Combination With Pegylated Interferon, vs Entecavir In uPA\/SCID Mice With Humanized Livers and HBV Infection","volume":"154","author":"Klumpp","year":"2018","journal-title":"Gastroenterology"},{"key":"B152","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.11.036","article-title":"Inhibition of Hepatitis B Virus Gene Expression: A Step Towards Functional Cure","volume":"68","author":"Zoulim","year":"2018","journal-title":"J Hepatol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.733364\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T04:53:59Z","timestamp":1630990439000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.733364\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,7]]},"references-count":152,"alternative-id":["10.3389\/fimmu.2021.733364"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.733364","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,7]]},"article-number":"733364"}}