{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T19:26:26Z","timestamp":1786303586482,"version":"build-2736575974"},"reference-count":21,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T00:00:00Z","timestamp":1711756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Medicine and Pharmacy Carol Davila"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>Pegylated interferon alpha 2a continues to be used for the treatment of chronic hepatitis D. The reported on-treatment virologic response varies between 17 and 47%, with relapses in more than 50% of these patients. No stopping rules have been defined, and the duration of the treatment is not clearly established, but it should be between 48 and 96 weeks. In total, 76 patients with compensated liver disease treated with peg-interferon according to the Romanian National protocol for the treatment of hepatitis D were retrospectively included. The duration of treatment was up to 96 weeks, with the following stopping rules: less than a 2 log HDV RNA decrease by week 24 and less than a 1 log decrease every 6 months afterwards. Six months after stopping the treatment, it can be restarted for unlimited cycles. The inclusion criteria were aged above 18, HBs Ag-positive, HDV RNA detectable, ALT above ULN and\/or liver fibrosis at least F1 at liver biopsy, or Fibrotest and\/or Fibroscan higher than 7 KPa and\/or inflammation at least A1 at liver biopsy or Fibrotest. We monitored our patients for a total period of 4 years (including those that repeated the cycle). After the first 6 months of treatment, 27 patients (35.5%) had a greater than 2 log HDV RNA decrease, 19 of them achieving undetectable HDV RNA. Seventeen patients (22.3%) had undetectable HDV RNA 24 weeks after stopping 96 weeks of treatment, and none relapsed in the following 2 years. Of these 17 patients, 6 were cirrhotic, and 4 had F3. Undetectable HDV RNA at 24 weeks was the only parameter that predicted a long-term suppression of HDV RNA. In 49 patients, the treatment was stopped after 6 months according to protocol, but it was restarted 6 months later. Five of these patients finished a 48-week course of treatment; none achieved undetectable HDV RNA. During the first course of therapy, 45 patients had at least one moderate adverse reaction to treatment. In one patient, the treatment was stopped due to a serious adverse event (osteomyelitis). Treatment doses had to be reduced in 29 patients. The virologic response at week 24 can select the patients who will benefit from continuing the treatment from those who should be changed to another type of medication when available.<\/jats:p>","DOI":"10.3390\/tropicalmed9040073","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T13:44:52Z","timestamp":1711892692000},"page":"73","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Results of Response-Guided Therapy with Pegylated Interferon Alpha 2a in Chronic Hepatitis B and D"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3994-5020","authenticated-orcid":false,"given":"George S.","family":"Gherlan","sequence":"first","affiliation":[{"name":"Infectious Diseases Department, Universitatea de Medicina si Farmacie \u201dCarol Davila\u201d, 050474 Bucuresti, Romania"},{"name":"Infectious Diseases Department, Spitalul Clinic de Boli Infectioase si Tropicale \u201dDr. Victor Babes\u201d, 030303 Bucuresti, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Lazar","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Universitatea de Medicina si Farmacie \u201dCarol Davila\u201d, 050474 Bucuresti, Romania"},{"name":"Infectious Diseases Department, Spitalul Clinic de Boli Infectioase si Tropicale \u201dDr. Victor Babes\u201d, 030303 Bucuresti, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augustina","family":"Culinescu","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Spitalul Clinic de Boli Infectioase si Tropicale \u201dDr. Victor Babes\u201d, 030303 Bucuresti, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Smadu","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Spitalul Clinic de Boli Infectioase si Tropicale \u201dDr. Victor Babes\u201d, 030303 Bucuresti, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea R.","family":"Vatafu","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Universitatea de Medicina si Farmacie \u201dCarol Davila\u201d, 050474 Bucuresti, Romania"},{"name":"Infectious Diseases Department, Spitalul Clinic de Boli Infectioase si Tropicale \u201dDr. Victor Babes\u201d, 030303 Bucuresti, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corneliu P.","family":"Popescu","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Universitatea de Medicina si Farmacie \u201dCarol Davila\u201d, 050474 Bucuresti, Romania"},{"name":"Infectious Diseases Department, Spitalul Clinic de Boli Infectioase si Tropicale \u201dDr. Victor Babes\u201d, 030303 Bucuresti, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6482-3386","authenticated-orcid":false,"given":"Simin A.","family":"Florescu","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Universitatea de Medicina si Farmacie \u201dCarol Davila\u201d, 050474 Bucuresti, Romania"},{"name":"Infectious Diseases Department, Spitalul Clinic de Boli Infectioase si Tropicale \u201dDr. Victor Babes\u201d, 030303 Bucuresti, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanoil","family":"Ceausu","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Universitatea de Medicina si Farmacie \u201dCarol Davila\u201d, 050474 Bucuresti, Romania"},{"name":"Infectious Diseases Department, Spitalul Clinic de Boli Infectioase si Tropicale \u201dDr. Victor Babes\u201d, 030303 Bucuresti, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petre I.","family":"Calistru","sequence":"additional","affiliation":[{"name":"Infectious Diseases Department, Universitatea de Medicina si Farmacie \u201dCarol Davila\u201d, 050474 Bucuresti, Romania"},{"name":"Infectious Diseases Department, Spitalul Clinic de Boli Infectioase si Tropicale \u201dDr. Victor Babes\u201d, 030303 Bucuresti, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a021550","DOI":"10.1101\/cshperspect.a021550","article-title":"Hepatitis D virus coinfection and superinfection","volume":"4","author":"Negro","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2023). EASL Clinical Practice Guidelines on hepatitis delta virus. J. Hepatol., 79, 433\u2013460.","DOI":"10.1016\/j.jhep.2023.05.001"},{"key":"ref_3","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_4","doi-asserted-by":"crossref","unstructured":"Mertowska, P., Smolak, K., Mertowski, S., and Grywalska, E. (2023). Immunomodulatory Role of Interferons in Viral and Bacterial Infections. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241210115"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.3389\/fimmu.2018.02061","article-title":"The Dual Nature of Type I and Type II Interferons","volume":"9","author":"Lee","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1002\/hep4.1821","article-title":"HBcrAg Levels Are Associated With Virological Response to Treatment With Interferon in Patients With Hepatitis Delta","volume":"6","author":"Sandmann","year":"2022","journal-title":"Hepatol. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/liv.14740","article-title":"Residual low HDV viraemia is associated HDV RNA relapse after PEG-IFNa-based antiviral treatment of hepatitis delta: Results from the HIDIT-II study","volume":"41","author":"Bremer","year":"2021","journal-title":"Liver Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/liv.15410","article-title":"Interferon-based treatment of chronic hepatitis D","volume":"43","author":"Sandmann","year":"2023","journal-title":"Liver Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1002\/hep.21325","article-title":"Efficacy of peginterferon alpha-2b in chronic hepatitis delta: Relevance of quantitative RT-PCR for follow-up","volume":"44","author":"Castelnau","year":"2006","journal-title":"Hepatology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1111\/j.1478-3231.2006.01279.x","article-title":"Treatment of chronic hepatitis delta with pegylated interferon-alpha2b","volume":"26","author":"Erhardt","year":"2006","journal-title":"Liver Int."},{"key":"ref_11","first-page":"377","article-title":"Weight-based dosing regimen of peg-interferon \u03b1-2b for chronic hepatitis delta: A multicenter Romanian trial","volume":"20","author":"Gheorghe","year":"2011","journal-title":"J. Gastrointest. Liver Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"731","DOI":"10.5812\/kowsar.1735143X.2462","article-title":"Treatment of chronic delta hepatitis: A nine-year retrospective analysis","volume":"11","author":"Gulsun","year":"2011","journal-title":"Hepat. Mon."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"561","DOI":"10.3851\/IMP2381","article-title":"Efficacy of pegylated interferon-\u03b1 treatment for 24 months in chronic delta hepatitis and predictors of response","volume":"18","author":"Karaca","year":"2013","journal-title":"Antivir. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e24366","DOI":"10.5812\/hepatmon.24366","article-title":"Pegylated Interferon \u03b1 Therapy in Chronic Delta Hepatitis: A One-Center Experience","volume":"15","author":"Bahcecioglu","year":"2015","journal-title":"Hepat. Mon."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1002\/jmv.25438","article-title":"Antiviral treatment with pegylated interferon and clinical outcomes in a cohort of immigrants patients affected by hepatitis delta: A retrospective analysis","volume":"91","author":"Boglione","year":"2019","journal-title":"J. Med. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1056\/NEJMoa0912696","article-title":"Peginterferon plus adefovir versus either drug alone for hepatitis delta","volume":"364","author":"Wedemeyer","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S1473-3099(18)30663-7","article-title":"Peginterferon alfa-2a plus tenofovir disoproxil fumarate for hepatitis D (HIDIT-II): A randomised, placebo controlled, phase 2 trial","volume":"19","author":"Wedemeyer","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/hep.27102","article-title":"Late HDV RNA relapse after peginterferon alpha-based therapy of chronic hepatitis delta","volume":"60","author":"Heidrich","year":"2014","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1111\/jvh.13366","article-title":"Ten-year follow-up of a randomized controlled clinical trial in chronic hepatitis delta","volume":"27","author":"Wranke","year":"2020","journal-title":"J. Viral Hepat."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rong, Y., Ju, X., Sun, P., and Wang, Y. (2023). Comparative effectiveness of seven interventions for chronic hepatitis D: A systematic review and network meta-analysis of randomized controlled trials. BMC Infect. Dis., 23.","DOI":"10.1186\/s12879-023-08718-7"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/ueg2.12494","article-title":"Management of chronic HBV-HDV patients chronic HBV-HDV infection: A review on new management options","volume":"12","author":"Buti","year":"2023","journal-title":"United Eur. Gastroenterol. 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