{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:09:47Z","timestamp":1792271387835,"version":"4.4.0"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Proof\u2010of\u2010concept studies demonstrated lonafarnib (LNF), a first\u2010in\u2010class oral prenylation inhibitor, efficacy in patients infected with HDV. The lonafarnib with ritonavir for HDV\u20102 (LOWR\u20102) study\u2019s aim was to identify optimal combination regimens of LNF\u00a0+\u00a0ritonavir (RTV) \u00b1 pegylated interferon alpha (PEG\u2010IFN\u03b1) with efficacy and tolerability for longer\u2010term dosing. Here we report the safety and efficacy at end of treatment for up to 24 weeks.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Fifty\u2010five patients with chronic HDV were consecutively enrolled in an open\u2010label, single\u2010center, phase 2 dose\u2010finding study. There were three main treatment groups: high\u2010dose LNF (LNF\u00a0\u2265\u00a075 mg by mouth [po] twice daily [bid]\u00a0+\u00a0RTV) (<jats:italic toggle=\"yes\">n<\/jats:italic>\u00a0=\u00a019, 12 weeks); all\u2010oral low\u2010dose LNF (LNF 25 or 50 mg po bid\u00a0+\u00a0RTV) (<jats:italic toggle=\"yes\">n<\/jats:italic>\u00a0=\u00a024, 24 weeks), and combination low\u2010dose LNF with PEG\u2010IFN\u03b1 (LNF 25 or 50 mg po bid\u00a0+\u00a0RTV\u00a0+\u00a0PEG\u2010IFN\u03b1) (<jats:italic toggle=\"yes\">n<\/jats:italic>\u00a0=\u00a012, 24 weeks). The primary endpoint, \u22652 log<jats:sub>10<\/jats:sub> decline or &lt; lower limit of quantification of HDV\u2010RNA from baseline at end of treatment, was reached in 46% (6 of 13) and 89% (8 of 9) of patients receiving the all\u2010oral regimen of LNF 50 mg bid\u00a0+\u00a0RTV, and combination regimens of LNF (25 or 50 mg bid)\u00a0+\u00a0RTV\u00a0+\u00a0PEG\u2010IFN\u03b1, respectively. In addition, multiple patients experienced well\u2010tolerated transient posttreatment alanine aminotransferase increases, resulting in HDV\u2010RNA negativity and alanine aminotransferase normalization. The proportions of grade 2 and 3 gastrointestinal adverse events in the high\u2010dose versus low\u2010dose groups were 49% (37 of 76) and only 22% (18 of 81), respectively.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>LNF, boosted with low\u2010dose RTV, is a promising all\u2010oral therapy, and maximal efficacy is achieved with PEG\u2010IFN\u03b1 addition. The identified optimal regimens support a phase 3 study of LNF for the treatment of HDV.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32259","type":"journal-article","created":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T11:28:03Z","timestamp":1638530883000},"page":"1551-1565","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":76,"title":["A phase 2 dose\u2010finding study of lonafarnib and ritonavir with or without interferon alpha for chronic delta hepatitis"],"prefix":"10.1097","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5419-7158","authenticated-orcid":false,"given":"Cihan","family":"Yurdaydin","sequence":"first","affiliation":[{"name":"Department of Gastroenterology,University of Ankara Medical School,Ankara,Turkey"},{"name":"Hepatology Institute,University of Ankara,Ankara,Turkey"},{"name":"Department of Gastroenterology and Hepatology,Ko\u00e7 University Medical School,Istanbul,Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onur","family":"Keskin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,University of Ankara Medical School,Ankara,Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esra","family":"Yurdcu","sequence":"additional","affiliation":[{"name":"Hepatology Institute,University of Ankara,Ankara,Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysun","family":"\u00c7ali\u015fkan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,University of Ankara Medical School,Ankara,Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soner","family":"\u00d6nem","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,University of Ankara Medical School,Ankara,Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih","family":"Karakaya","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,University of Ankara Medical School,Ankara,Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c7a\u011fda\u015f","family":"Kalkan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,University of Ankara Medical School,Ankara,Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ersin","family":"Karatayli","sequence":"additional","affiliation":[{"name":"Hepatology Institute,University of Ankara,Ankara,Turkey"},{"name":"Department of Medicine II,Saarland University Medical Center,Saarland University,Homburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senem","family":"Karatayli","sequence":"additional","affiliation":[{"name":"Hepatology Institute,University of Ankara,Ankara,Turkey"},{"name":"Department of Medicine II,Saarland University Medical Center,Saarland University,Homburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Choong","sequence":"additional","affiliation":[{"name":"Eiger BioPharmaceuticals, Inc.,Palo Alto,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Apelian","sequence":"additional","affiliation":[{"name":"Eiger BioPharmaceuticals, Inc.,Palo Alto,California,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Koh","sequence":"additional","affiliation":[{"name":"Translational Hepatology Section,Liver Diseases Branch,National Institute of Diabetes and Digestive and Kidney Diseases,National Institutes of Health,Bethesda,Maryland,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"Heller","sequence":"additional","affiliation":[{"name":"Translational Hepatology Section,Liver Diseases Branch,National Institute of Diabetes and Digestive and Kidney Diseases,National Institutes of Health,Bethesda,Maryland,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramazan","family":"Idilman","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,University of Ankara Medical School,Ankara,Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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