{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:31:23Z","timestamp":1789133483494,"version":"build-2803163510"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T00:00:00Z","timestamp":1741996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>We analysed the frequency, severity and impact of hepatitis flares in a large Phase 2 study investigating pegylated interferon\u2010alfa\u20102a (PEG\u2010IFNa) for the treatment of hepatitis D. In the HIDIT\u2010II study, 120 patients were treated for 96\u2009weeks with PEG\u2010IFNa (180\u2009\u03bcg weekly) in combination with tenofovir disoproxil fumarate (TDF, 300\u2009mg once daily) or placebo. Hepatitis flares were defined as ALT increases above 10 times the upper limit of normal or increases of more than 2.5\u2010fold above baseline or nadir values. ALT flares occurred in 28 patients (23%) during treatment (&lt;\u200996) and in 14 patients post\u2010treatment until follow\u2010up Week\u200924. There were no differences in the flare frequency between the two treatment arms (12 PEG\u2010IFNa\u2009+\u2009placebo vs. 16 PEG\u2010IFNa\u2009+\u2009TDF). The frequency of ALT increases did not differ between cirrhotic and noncirrhotic patients. None of the patients with cirrhosis experienced liver decompensation during or after a flare. Fifty\u2010four per cent of the patients with ALT flare experienced a decrease in HDV RNA (&gt;\u20091\u2009log10 cop\/ml) during subsequent study visits. Mean ALT levels early during treatment were higher in patients with HBsAg loss at follow\u2010up Week\u200924. More than a third of hepatitis D patients undergoing PEG\u2010IFNa therapy may experience ALT flares during or after treatment. ALT flares in this study posed no obvious safety risk to patients and should not lead to premature withdrawal from treatment. If ALT flares may be beneficial in single patients requires further investigation.<\/jats:p><jats:p>Clinical Trial Registration: NCT00932971, EudraCT 2008\u2013005560\u201013.<\/jats:p>","DOI":"10.1111\/jvh.70022","type":"journal-article","created":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T07:39:46Z","timestamp":1742024386000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Frequency, Severity and Impact of Pegylated Interferon Alpha\u2013Associated Flares in Hepatitis D Infection"],"prefix":"10.1111","volume":"32","author":[{"given":"Svenja","family":"Hardtke","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology Hannover Medical School  Hannover Germany"},{"name":"German Center for Infectious Disease Research (DZIF) HepNet Study\u2010House\/German Liver Foundation  Hannover Germany"},{"name":"University Hospital Hamburg Eppendorf Institute for Infection Research and Vaccine Development  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5419-7158","authenticated-orcid":false,"given":"Cihan","family":"Yurdaydin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Ankara University Medical School  Ankara Turkey"},{"name":"Department of Gastroenterology &amp; Hepatology Koc University Medical School  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florin A.","family":"Caruntu","sequence":"additional","affiliation":[{"name":"Institutul de Boli Infectioase  Bucharest Romania"},{"name":"D\u2010SOLVE Consortium, an EU Horizon Europe Funded Project (No 101057917)  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela G.","family":"Curescu","sequence":"additional","affiliation":[{"name":"Spitalul Clinic de Boli Infectioase Si  Timisoara Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendal","family":"Yalcin","sequence":"additional","affiliation":[{"name":"Dicle University Medical Hospitals  Diyarbakir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulus S.","family":"Akarca","sequence":"additional","affiliation":[{"name":"Ege University Medical Faculty Hospital  Izmir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selim","family":"G\u00fcrel","sequence":"additional","affiliation":[{"name":"Uluda\u011f University Medical School  Bursa Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Zeuzem","sequence":"additional","affiliation":[{"name":"Department of Medicine University Hospital, Goethe\u2010University  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Erhardt","sequence":"additional","affiliation":[{"name":"Heinrich Heine University  D\u00fcsseldorf Germany"},{"name":"Petrus Hospital  Wuppertal Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"L\u00fcth","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Diabetology and Hepatology University Hospital Brandenburg, Medical School (Theodor Fontane)  Brandenburg Germany"},{"name":"Health Sciences, Brandenburg University of Technology Cottbus\u2014Senftenberg, the Brandenburg Medical School Theodor Fontane and the University of Potsdam  Potsdam Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3518-4060","authenticated-orcid":false,"given":"George V.","family":"Papatheodoridis","sequence":"additional","affiliation":[{"name":"First Department of Gastroenterology Medical School, National and Kapodistrian University of Athens, General Hospital of Athens \u201cLaiko\u201d  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Port","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Manns","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9141-8001","authenticated-orcid":false,"given":"Markus","family":"Cornberg","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology Hannover Medical School  Hannover Germany"},{"name":"German Center for Infectious Disease Research (DZIF) HepNet Study\u2010House\/German Liver Foundation  Hannover Germany"},{"name":"D\u2010SOLVE Consortium, an EU Horizon Europe Funded Project (No 101057917)  Hannover Germany"},{"name":"German Center for Infectious Disease Research (DZIF); 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