{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:46:16Z","timestamp":1760240776681,"version":"build-2065373602"},"reference-count":27,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T00:00:00Z","timestamp":1568592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TRR60"],"award-info":[{"award-number":["TRR60"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Hepatitis B virus (HBV) reactivation in immunosuppressed patients can cause considerable morbidity and mortality. The aim of our study was to evaluate factors associated with acute liver failure (ALF) in HBV reactivation. Clinical, laboratory, and virological data of 87 patients with HBV reactivation were analyzed retrospectively. Teno torque virus (TTV) plasma loads were measured as a measure of immune competence. HBV genomes isolated from 47 patients were analyzed by next-generation sequencing. A functional analysis of identified HBsAg mutants was performed. In patients with ALF the diagnosis was significantly later confirmed than in the non-ALF group. Patients diagnosed during immunosuppression had a milder clinical course compared to later diagnosed patients (p = 0.018, OR = 4.17). TTV viral loads did not differ significantly between the two groups. The HBV genomes isolated from ALF patients had higher viral complexity. A mutation in C-region of HBsAg (L216*), was associated with reduced HBsAg production and secretion. Patients diagnosed with HBV reactivation during immunosuppression had a milder clinical course compared to patients diagnosed during immune reconstitution. ALF was associated with higher viral complexity. An HBsAg mutation (L216*) was found to be more frequent in ALF patients and was associated with reduced HBsAg production and secretion.<\/jats:p>","DOI":"10.3390\/v11090863","type":"journal-article","created":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T03:31:46Z","timestamp":1568691106000},"page":"863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Clinical and Virological Aspects of HBV Reactivation: A Focus on Acute Liver Failure"],"prefix":"10.3390","volume":"11","author":[{"given":"Olympia E.","family":"Anastasiou","sequence":"first","affiliation":[{"name":"Institute of Virology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Theissen","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biophysics, University of Duisburg-Essen, 45117 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Verheyen","sequence":"additional","affiliation":[{"name":"Institute of Virology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Bleekmann","sequence":"additional","affiliation":[{"name":"Institute of Virology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heiner","family":"Wedemeyer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Essen, 45147 Essen, Germany"},{"name":"German Center for Infection Research, DZIF, 38124 Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5417-9307","authenticated-orcid":false,"given":"Marek","family":"Widera","sequence":"additional","affiliation":[{"name":"Institute of Virology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Ciesek","sequence":"additional","affiliation":[{"name":"Institute of Virology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"German Center for Infection Research, DZIF, 38124 Braunschweig, Germany"},{"name":"Institute of Medical Virology, University Hospital Frankfurt, 60596 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,16]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nrgastro.2013.216","article-title":"Management of patients with hepatitis b who require immunosuppressive therapy","volume":"11","author":"Hwang","year":"2014","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1002\/hep.28667","article-title":"Detection of hepatitis b virus DNA in the blood of a stem cell donor after granulocyte colony-stimulating factor treatment","volume":"64","author":"Punzel","year":"2016","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Salpini, R., Battisti, A., Colagrossi, L., Di Carlo, D., Fabeni, L., Piermatteo, L., Cerva, C., Lichtner, M., Mastroianni, C., and Marignani, M. (2019). A snapshot of virological presentation and outcome of immunosuppression-driven hbv reactivation from real clinical practice: Evidence of a relevant risk of death and evolution from silent to chronic infection. J. Viral. Hepat.","DOI":"10.1111\/jvh.13101"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S156","DOI":"10.1002\/hep.22945","article-title":"Reactivation of hepatitis b","volume":"49","author":"Hoofnagle","year":"2009","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1099\/jmm.0.000823","article-title":"Role of bk polyomavirus (bkv) and torque teno virus (ttv) in liver transplant recipients with renal impairment","volume":"67","author":"Herrmann","year":"2018","journal-title":"J. Med. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1093\/infdis\/jiy452","article-title":"Torque teno virus as a novel biomarker targeting the efficacy of immunosuppression after lung transplantation","volume":"218","author":"Jaksch","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1056\/NEJMra021844","article-title":"Drug-induced hepatotoxicity","volume":"349","author":"Lee","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_9","first-page":"912","article-title":"Hepatic injury during doxorubicin therapy","volume":"108","author":"Aviles","year":"1984","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1086\/431586","article-title":"The hepatotoxicity of antifungal medications in bone marrow transplant recipients","volume":"41","author":"Fischer","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.cgh.2016.06.008","article-title":"Hbv-associated acute liver failure after immunosuppression and risk of death","volume":"15","author":"Karvellas","year":"2017","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1002\/hep.30279","article-title":"Clinical outcome and viral genome variability of hepatitis b virus-induced acute liver failure","volume":"69","author":"Anastasiou","year":"2019","journal-title":"Hepatology"},{"key":"ref_13","first-page":"1628","article-title":"Fulminant hepatitis associated with hepatitis b virus e antigen-negative infection: Importance of host factors","volume":"22","author":"Karayiannis","year":"1995","journal-title":"Hepatology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1056\/NEJM199106133242405","article-title":"A hepatitis b virus mutant associated with an epidemic of fulminant hepatitis","volume":"324","author":"Liang","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1002\/hep.27604","article-title":"Hepatitis b surface antigen genetic elements critical for immune escape correlate with hepatitis b virus reactivation upon immunosuppression","volume":"61","author":"Salpini","year":"2015","journal-title":"Hepatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1002\/hep.20703","article-title":"Aasld position paper: The management of acute liver failure","volume":"41","author":"Polson","year":"2005","journal-title":"Hepatology"},{"key":"ref_17","unstructured":"Beggel, B.B.J., D\u00e4umer, M., Hoffmann, D., Kaiser, R., Lengauer , T., Schuldenzucker , U., Schl\u00fcter, E., and Verheyen, J. (2009). Geno2pheno [hbv]. http:\/\/hbv.bioinf.mpi-inf.mpg.de\/index.php, Max Planck Institute for Informatics."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"D566","DOI":"10.1093\/nar\/gks1022","article-title":"Hbvdb: A knowledge database for hepatitis b virus","volume":"41","author":"Hayer","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Nishijima, N., Marusawa, H., Ueda, Y., Takahashi, K., Nasu, A., Osaki, Y., Kou, T., Yazumi, S., Fujiwara, T., and Tsuchiya, S. (2012). Dynamics of hepatitis b virus quasispecies in association with nucleos(t)ide analogue treatment determined by ultra-deep sequencing. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035052"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.jhep.2014.04.041","article-title":"Hepatitis b virus pres\/s gene variants: Pathobiology and clinical implications","volume":"61","author":"Pollicino","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/S0140-6736(75)90897-1","article-title":"Fulminant hepatic failure in leukaemia and choriocarcinoma related to withdrawal of cytotoxic drug therapy","volume":"306","author":"Galbraith","year":"1975","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1111\/hepr.12496","article-title":"Multicenter cooperative case survey of hepatitis b virus reactivation by chemotherapeutic agents","volume":"45","author":"Takahashi","year":"2015","journal-title":"Hepatol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.bbmt.2017.09.020","article-title":"Torquetenovirus dynamics and immune marker properties in patients following allogeneic hematopoietic stem cell transplantation: A prospective longitudinal study","volume":"24","author":"Wohlfarth","year":"2018","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1136\/gut.2008.174029","article-title":"Hepatitis b virus protein pres2 potentially promotes hcc development via its transcriptional activation of htert","volume":"58","author":"Luan","year":"2009","journal-title":"Gut"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1007\/s10495-007-0114-4","article-title":"The hepatitis b virus protein mhbs(t) sensitizes hepatoma cells to trail-induced apoptosis through erk2","volume":"12","author":"Liang","year":"2007","journal-title":"Apoptosis"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1096\/fj.02-0537fje","article-title":"Involvement of trail and its receptors in viral hepatitis","volume":"17","author":"Mundt","year":"2003","journal-title":"FASEB J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.bbrc.2006.11.024","article-title":"Blockade of trail pathway ameliorates hbv-induced hepatocyte apoptosis in an acute hepatitis model","volume":"352","author":"Liu","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/9\/863\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:20:42Z","timestamp":1760188842000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/9\/863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,16]]},"references-count":27,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["v11090863"],"URL":"https:\/\/doi.org\/10.3390\/v11090863","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2019,9,16]]}}}