{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:26:49Z","timestamp":1790627209457,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,8,29]],"date-time":"2021-08-29T00:00:00Z","timestamp":1630195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015383","name":"Stichting voor Lever- en Maag-Darm Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015383","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["18B2821N"],"award-info":[{"award-number":["18B2821N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hepatitis E viruses (HEV) are an underestimated global cause of enterically transmitted viral hepatitis, which may persist in immunocompromised hosts, posing a risk for progressive liver fibrosis with limited treatment options. We previously established liver\u2010humanized mice as a model for chronic HEV infections, which can be cleared by a 2\u2010week pegylated (peg)\u2010Interferon(IFN)\u03b1 treatment course. However, severe side effects may hamper the use of IFN\u03b1 in immunocompromised transplant recipient patients. IFN\u03bb may be a valuable alternative, as its receptor is less ubiquitously expressed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>In this study, we assess the in vitro and in vivo potency of pegIFN\u03bb to induce innate immune signalling in liver cells and to clear a persistent HEV infection in liver\u2010humanized mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods &amp; Results<\/jats:title><jats:p>We found that human liver cells expressed the IFN\u03bb receptor (IFNLR1) and are responsive to pegIFN\u03bb. Treatment with pegIFN\u03bb of liver\u2010humanized mice persistently infected with HEV genotype 3 showed that pegIFN\u03bb was well tolerated. Dose escalation studies showed that although HEV was not cleared at pegIFN\u03bb doses up to 0.12\u00a0mg\/kg for a maximum of 8\u00a0weeks, a dose of 0.3\u00a0mg\/kg pegIFN\u03bb treatment resulted in complete clearance of HEV antigen and HEV RNA from the liver in 8 out of 9 liver\u2010humanized mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>PegIFN\u03bb is well tolerated in mice and leads to clearance of a persistent HEV infection in liver\u2010humanized mice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15033","type":"journal-article","created":{"date-parts":[[2021,8,15]],"date-time":"2021-08-15T17:02:45Z","timestamp":1629046965000},"page":"2866-2873","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Treatment induced clearance of hepatitis E viruses by interferon\u2010lambda in liver\u2010humanized mice"],"prefix":"10.1111","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8585-5889","authenticated-orcid":false,"given":"Gulce","family":"Sari","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia E.","family":"Mulders","sequence":"additional","affiliation":[{"name":"Department of Viroscience Erasmus University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingting","family":"Zhu","sequence":"additional","affiliation":[{"name":"Center for Vaccines and Immunity The Research Institute at Nationwide Children\u2019s Hospital Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gertine W.","family":"van Oord","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus 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