{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T05:22:23Z","timestamp":1768281743973,"version":"3.49.0"},"reference-count":54,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T00:00:00Z","timestamp":1658361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cIDENTIFICAZIONE DEI FATTORI DEMOGRAFICI, CLINICI, VIROLOGICI, GENETICI, IMMUNOLOGICI E SIEROLOGICI ASSOCIATI AD OUTCOME SFAVOREVOLE NEI SOGGETTI CON COVID-19\u201d, Regione Campania, Italy","award":["DGR n. 140 del 17 marzo 2020"],"award-info":[{"award-number":["DGR n. 140 del 17 marzo 2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Universal hepatitis B virus (HBV) vaccination has been applied for years in most countries, but HBV infection remains an unresolved public health problem worldwide, with over one-third of the world\u2019s population infected during their lifetime and approximately 248 million hepatitis B surface antigen (HBsAg) chronic carriers. HBV infection may reactivate with symptomatic and sometimes life-threatening clinical manifestations due to a reduction in the immune response of various origins, due to chemotherapy or immunosuppressive therapy, treatments increasingly practiced worldwide. SARS-CoV-2 and its COVID-19 associated disease have introduced new chances for HBV reactivation due to the use of dexamethasone and tocilizumab to counteract the cytokine storm. This could and should be prevented by accurate screening of HBV serologic markers and adequate pharmacologic prophylaxis. This article describes the case of a patient with COVID-19 who developed HBV reactivation and died of liver failure and analyzes published data on this setting to provide useful information to physicians who manage these patients during the SARS-CoV-2 pandemic.<\/jats:p>","DOI":"10.3390\/pathogens11070816","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T22:38:50Z","timestamp":1658443130000},"page":"816","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["COVID-19 as Another Trigger for HBV Reactivation: Clinical Case and Review of Literature"],"prefix":"10.3390","volume":"11","author":[{"given":"Caterina","family":"Sagnelli","sequence":"first","affiliation":[{"name":"Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania \u201cLuigi Vanvitelli\u201d, 80134 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Montella","sequence":"additional","affiliation":[{"name":"Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania \u201cLuigi Vanvitelli\u201d, 80134 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierantonio","family":"Grimaldi","sequence":"additional","affiliation":[{"name":"Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania \u201cLuigi Vanvitelli\u201d, 80134 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariantonietta","family":"Pisaturo","sequence":"additional","affiliation":[{"name":"Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania \u201cLuigi Vanvitelli\u201d, 80134 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loredana","family":"Alessio","sequence":"additional","affiliation":[{"name":"Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania \u201cLuigi Vanvitelli\u201d, 80134 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"De Pascalis","sequence":"additional","affiliation":[{"name":"Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania \u201cLuigi Vanvitelli\u201d, 80134 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2817-8436","authenticated-orcid":false,"given":"Evangelista","family":"Sagnelli","sequence":"additional","affiliation":[{"name":"Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania \u201cLuigi Vanvitelli\u201d, 80134 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5897-4949","authenticated-orcid":false,"given":"Nicola","family":"Coppola","sequence":"additional","affiliation":[{"name":"Department of Mental Health and Public Medicine, Section of Infectious Diseases, University of Campania \u201cLuigi Vanvitelli\u201d, 80134 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1136\/annrheumdis-2021-221650","article-title":"Average corticosteroid dose and risk for HBV reactivation and hepatitis flare in patients with resolved hepatitis B infection","volume":"81","author":"Zhong","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2931402","DOI":"10.1155\/2018\/2931402","article-title":"Recent Advances in HBV Reactivation Research","volume":"2018","author":"Guo","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"m2200","DOI":"10.1136\/bmj.m2200","article-title":"Hepatitis B virus persistence and reactivation","volume":"370","author":"Shi","year":"2020","journal-title":"BMJ."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.idc.2020.02.009","article-title":"Hepatitis B Virus Reactivation Potentiated by Biologics","volume":"34","author":"Ogawa","year":"2020","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.micpath.2017.12.014","article-title":"HBV reactivation in rheumatic diseases patients under therapy: A meta-analysis","volume":"114","author":"Moghoofei","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3299","DOI":"10.3748\/wjg.v25.i26.3299","article-title":"Reactivation of hepatitis B virus infection in patients with hemo-lymphoproliferative diseases, and its prevention","volume":"25","author":"Sagnelli","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10274","DOI":"10.3748\/wjg.v21.i36.10274","article-title":"Hepatitis B virus reactivation associated with antirheumatic therapy: Risk and prophylaxis recommendations","volume":"21","author":"Mori","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.cmi.2020.12.011","article-title":"Italian Society of Infectious and Tropical Diseases. Therapeutic strategies for severe COVID-19: A position paper from the Italian Society of Infectious and Tropical Diseases (SIMIT)","volume":"27","author":"Mussini","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1080\/14397595.2020.1832731","article-title":"Updates on management strategies of hepatitis B virus reactivation in patients with resolved hepatitis virus B infection undergoing immunosuppressive therapy in rheumatology and the current situation in Niigata Rheumatic Center","volume":"31","author":"Ito","year":"2021","journal-title":"Mod. Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.tim.2016.05.006","article-title":"Control and Eradication Strategies of Hepatitis B Virus","volume":"24","author":"Shih","year":"2016","journal-title":"Trends Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"743","DOI":"10.7326\/0003-4819-156-10-201205150-00013","article-title":"Reactivation of Hepatitis B During Immunosuppressive Therapy: Potentially Fatal Yet Preventable","volume":"156","author":"Lok","year":"2012","journal-title":"Ann. Intern. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1186\/s40425-019-0808-5","article-title":"Hepatitis B virus reactivation in cancer patients with positive Hepatitis B surface antigen undergoing PD-1 inhibition","volume":"7","author":"Zhang","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"384","DOI":"10.4254\/wjh.v6.i6.384","article-title":"Clinical impact of occult hepatitis B virus infection in immunosuppressed patients","volume":"6","author":"Sagnelli","year":"2014","journal-title":"World J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Russo, A., Pisaturo, M., Palladino, R., Maggi, P., Numis, F.G., Gentile, I., Sangiovanni, V., Esposito, V., Punzi, R., and Calabria, G. (2022). Prognostic Value of Transaminases and Bilirubin Levels at Admission to Hospital on Disease Progression and Mortality in Patients with COVID-19\u2014An Observational Retrospective Study. Pathogens, 11.","DOI":"10.3390\/pathogens11060652"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/S2468-1253(20)30057-1","article-title":"Liver injury in COVID-19: Management and challenges","volume":"5","author":"Zhang","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1016\/j.cgh.2020.04.002","article-title":"Clinical Features of COVID-19-Related Liver Functional Abnormality","volume":"18","author":"Fan","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.jhep.2020.05.002","article-title":"SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19","volume":"73","author":"Wang","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e13338","DOI":"10.1111\/eci.13338","article-title":"COVID-19 and non-alcoholic fatty liver disease: Two intersecting pandemics","volume":"50","author":"Portincasa","year":"2020","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s12072-020-10054-w","article-title":"Clinical practice guidance for hepatology and liver transplant providers during the COVID-19 pandemic: APASL expert panel consensus recommendations","volume":"14","author":"Lau","year":"2020","journal-title":"Hepatol. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical Characteristics of Coronavirus Disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1001\/jama.2020.6775","article-title":"Presenting Characteristics, Comorbidities, and Outcomes among 5700 Patients Hospitalized with COVID-19 in the New York City Area","volume":"323","author":"Richardson","year":"2020","journal-title":"JAMA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.cgh.2020.06.017","article-title":"Characteristics of Liver Function in Patients With SARS-CoV-2 and Chronic HBV Coinfection","volume":"19","author":"Zou","year":"2021","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1111\/liv.14774","article-title":"Clinical characteristics of COVID-19 patients with hepatitis B virus infection-a retrospective study","volume":"41","author":"Liu","year":"2021","journal-title":"Liver Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1111\/jvh.13362","article-title":"Clinical characteristics in patients with SARS-CoV-2\/HBV co-infection","volume":"27","author":"Chen","year":"2020","journal-title":"J. Viral Hepat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5266","DOI":"10.12998\/wjcc.v9.i19.5266","article-title":"COVID-19 or treatment associated immunosuppression may trigger hepatitis B virus reactivation: A case report","volume":"9","author":"Wu","year":"2021","journal-title":"World J. Clin. Cases"},{"key":"ref_27","first-page":"e8645","article-title":"COVID-19 Induced Hepatitis B Virus Reactivation: A Novel Case from the United Arab Emirates","volume":"12","author":"Aldhaleei","year":"2020","journal-title":"Cureus"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/jvh.13410","article-title":"Low risk of hepatitis B reactivation in patients with severe COVID-19 who receive immunosuppressive therapy","volume":"28","author":"Miralpeix","year":"2021","journal-title":"J. Viral Hepat."},{"key":"ref_29","unstructured":"(2022, July 17). NIH Guidelines Coronavirus Disease 2019 (COVID-19) Treatment Guidelines, Available online: https:\/\/www.covid19treatmentguidelines.nih.gov\/."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s10238-020-00671-y","article-title":"Emerging treatment strategies for COVID-19 infection","volume":"21","author":"Gavriatopoulou","year":"2021","journal-title":"Clin. Exp. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10970","DOI":"10.1073\/pnas.2005615117","article-title":"Effective treatment of severe COVID-19 patients with tocilizumab","volume":"117","author":"Xu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sagnelli, C., Sica, A., Creta, M., Borsetti, A., Ciccozzi, M., and Sagnelli, E. (2022). Prevention of HBV Reactivation in Hemato-Oncologic Setting during COVID-19. Pathogens, 11.","DOI":"10.3390\/pathogens11050567"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.cmi.2021.11.007","article-title":"ESCMID COVID-19 living guidelines: Drug treatment and clinical management","volume":"28","author":"Bartoletti","year":"2022","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"m3379","DOI":"10.1136\/bmj.m3379","article-title":"A living WHO guideline on drugs for covid-19","volume":"370","author":"Agarwal","year":"2020","journal-title":"BMJ"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1001\/jamainternmed.2020.6252","article-title":"STOP-COVID Investigators. Association Between Early Treatment with Tocilizumab and Mortality Among Critically Ill Patients With COVID-19","volume":"181","author":"Gupta","year":"2021","journal-title":"JAMA Intern. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"RECOVERY Collaborative Group (2021). Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet, 397, 1637\u20131645.","DOI":"10.1101\/2021.02.11.21249258"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"662746","DOI":"10.3389\/fonc.2021.662746","article-title":"More Severe COVID-19 in Patients With Active Cancer: Results of a Multicenter Cohort Study","volume":"11","author":"Monari","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.dld.2018.09.010","article-title":"The burden of HBV infection in HCV patients in Italy and the risk of reactivation under DAA therapy","volume":"51","author":"Stroffolini","year":"2019","journal-title":"Dig. Liver Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1002\/jmv.22199","article-title":"Reactivation of overt and occult hepatitis B infection in various immunosuppressive settings","volume":"83","author":"Coppola","year":"2011","journal-title":"J. Med. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/liv.13496","article-title":"Potential risk of HBV reactivation in patients with resolved HBV infection undergoing direct-acting antiviral treatment for HCV","volume":"38","author":"Ogawa","year":"2018","journal-title":"Liver Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1007\/s15010-016-0891-1","article-title":"Occult HBV infection in the oncohematological setting","volume":"44","author":"Sagnelli","year":"2016","journal-title":"Infection"},{"key":"ref_42","first-page":"244","article-title":"Hepatitis B (HBV) reactivation in patients receiving biologic therapy for chronic inflammatory diseases in clinical practice","volume":"57","author":"Ridola","year":"2021","journal-title":"Ann. Ist. Super Sanita"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1007\/s10620-018-5042-3","article-title":"Hepatitis B Virus Screening and Reactivation in a National VA Cohort of Patients with Inflammatory Bowel Disease Treated with Tumor Necrosis Factor Antagonists","volume":"63","author":"Shah","year":"2018","journal-title":"Dig. Dis. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1053\/j.gastro.2017.02.009","article-title":"Hepatitis B Reactivation Associated ith Immune Suppressive and Biological Modifier Therapies: Current Concepts, Management Strategies, and Future Directions","volume":"152","author":"Loomba","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1136\/gut.2010.208413","article-title":"GETECCU (Grupo Espa\u00f1ol de Enfermedades de Crohn y Colitis Ulcerosa) Group. Liver dysfunction related to hepatitis B and C in patients with inflammatory bowel disease treated with immunosuppressive therapy","volume":"59","author":"Loras","year":"2010","journal-title":"Gut"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1038\/s41598-020-59406-4","article-title":"Moderate Risk of Hepatitis B Virus Reactivation in HbsAg-\/HbcAb+ Carriers Receiving Rituximab for Rheumatoid Arthritis","volume":"10","author":"Kuo","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4026","DOI":"10.1007\/s10620-020-06725-1","article-title":"Risk of Hepatitis B Virus Reactivation in Rheumatoid Arthritis Patients Undergoing Tocilizumab-Containing Treatment","volume":"66","author":"Kuo","year":"2021","journal-title":"Dig. Dis. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1111\/1756-185X.14217","article-title":"Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofacitinib","volume":"24","author":"Wang","year":"2021","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3851\/IMP3292","article-title":"HBV reactivation during direct-acting antiviral therapy in hepatitis B and C coinfected patients undergoing haemodialysis","volume":"24","author":"Wang","year":"2019","journal-title":"Antivir. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/1756-185X.14034","article-title":"Risk of hepatitis B reactivation in patients receiving anti-tumor necrosis factor-\u03b1 therapy","volume":"24","author":"Fidan","year":"2021","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jmii.2017.10.002","article-title":"Risk-stratified management strategies for HBV reactivation in RA patients receiving biological and targeted therapy: A narrative review","volume":"52","author":"Chen","year":"2019","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s15010-012-0305-y","article-title":"Transient reactivation of occult hepatitis B virus infection despite lamivudine prophylaxis in a patient treated for non-Hodgkin lymphoma","volume":"41","author":"Tonziello","year":"2013","journal-title":"Infection"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2017). EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J. Hepatol., 67, 370\u2013398.","DOI":"10.1016\/j.jhep.2017.03.021"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"706482","DOI":"10.3389\/fmed.2021.706482","article-title":"Risk of reactivation of hepatitis B virus (HBV) and tuberculosis (TB) and complications of hepatitis C virus (HCV) following Tocilizumab therapy: A systematic review to inform risk assessment in the COVID era","volume":"8","author":"Campbell","year":"2021","journal-title":"Front. Med."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/7\/816\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:55:10Z","timestamp":1760140510000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/7\/816"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,21]]},"references-count":54,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["pathogens11070816"],"URL":"https:\/\/doi.org\/10.3390\/pathogens11070816","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,21]]}}}