{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T14:58:38Z","timestamp":1781189918307,"version":"3.54.1"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005788","name":"Medical University of Vienna","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005788","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Wien Klin Wochenschr"],"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>Treatment options for chronic hepatitis\u00a0D (CHD) are limited in patients who do not respond to recommended treatment with bulevirtide\u202f\u00b1\u2009pegylated interferon. The use of REP 2139-Mg is a\u00a0novel treatment option that has recently demonstrated efficacy and safety in phase\u00a02 trials and a\u00a0compassionate access program that included three patients treated at the Vienna General Hospital with compensated advanced chronic liver disease and clinically significant portal hypertension (CSPH). Long-term outcome of CSPH patients treated with REP 2139-Mg is unknown; thus, surrogate endpoints are of interest in this population. In the 3 patients receiving REP 2139-Mg for 12 months at our center, we monitored the hepatic venous pressure gradient (HVPG) as the strongest prognostic surrogate biomarker in compensated cirrhosis at baseline, and after 3 and 12 months of treatment. The HVPG dynamics alongside additional liver function tests observed are summarized in this report and two out of three patients achieved undetectable hepatitis-D-virus(HDV)-RNA and low hepatitis B surface Antigen (HBsAg) following pronounced alanine aminotransferase (ALT) flares during REP 2139-Mg treatment. The first patient showed virologic non-response and no HVPG dynamics during treatment. The second patient developed jaundice upon treatment initiation, resulting in a\u00a0transient increase in HVPG despite virologic response. The third patient achieved virologic response that was paralleled by sustained reductions in HVPG.<\/jats:p>","DOI":"10.1007\/s00508-026-02748-2","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T14:08:48Z","timestamp":1781186928000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evolution of liver disease severity and portal hypertension during REP 2139-Mg treatment in 3\u00a0patients with chronic hepatitis\u00a0D"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2871-4147","authenticated-orcid":false,"given":"Mathias","family":"Jachs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattias","family":"Mandorfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Vaillant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Reiberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"2748_CR1","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.jhep.2025.10.029","volume":"84","author":"C Stern","year":"2026","unstructured":"Stern\u00a0C, Loustaud-Ratti\u00a0V, Yurdaydin\u00a0C, et\u00a0al. Safety and efficacy of REP 2139-Mg in patients with HDV-related advanced liver disease in an international compassionate access program. J\u00a0Hepatol. 2026;84:531\u201342.","journal-title":"J Hepatol"},{"key":"2748_CR2","doi-asserted-by":"crossref","unstructured":"Sandmann L, Jachs M, Tergast TL, et\u00a0al. Treatment response to bulevirtide is linked to amelioration of portal hypertension in patients with chronic hepatitis\u00a0D. JHEP Reports 2026;8.","DOI":"10.1016\/j.jhepr.2025.101643"},{"key":"2748_CR3","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1002\/hep.30885","volume":"71","author":"M Mandorfer","year":"2020","unstructured":"Mandorfer\u00a0M, Kozbial\u00a0K, Schwabl\u00a0P, et\u00a0al. Changes in Hepatic Venous Pressure Gradient Predict Hepatic Decompensation in Patients Who Achieved Sustained Virologic Response to Interferon-Free Therapy. Hepatology. 2020;71:1023\u201336.","journal-title":"Hepatology"},{"key":"2748_CR4","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.jhep.2024.03.005","volume":"81","author":"M Jachs","year":"2024","unstructured":"Jachs\u00a0M, Sandmann\u00a0L, Hartl\u00a0L, et\u00a0al. Validation of Baveno VII criteria and other non-invasive diagnostic algorithms for clinically significant portal hypertension in hepatitis delta. J\u00a0Hepatol. 2024;81:248\u201357.","journal-title":"J Hepatol"},{"key":"2748_CR5","unstructured":"Jachs M, Th\u00f6ne P, Odriozola A, et\u00a0al. Predicting hepatic decompensation using non-invasive tests in a\u00a0contemporary multicentre cohort of patients with cACLD. J\u00a0Hepatol 2025."},{"key":"2748_CR6","doi-asserted-by":"crossref","unstructured":"Jachs M, Carvalho T, Simbrunner B, et\u00a0al. Indocyanine Green Clearance Correlates With Biomarkers Reflecting Key Disease-Driving Mechanisms in Advanced Chronic Liver Disease and Predicts Acute-on-Chronic Liver Failure and Death. Aliment Pharmacol Ther 2025.","DOI":"10.1111\/apt.70447"},{"key":"2748_CR7","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/j.jhep.2020.10.004","volume":"74","author":"D Costa","year":"2021","unstructured":"Costa\u00a0D, Simbrunner\u00a0B, Jachs\u00a0M, et\u00a0al. Systemic inflammation increases across distinct stages of advanced chronic liver disease and correlates with decompensation and mortality. J\u00a0Hepatol. 2021;74:819\u201328.","journal-title":"J Hepatol"},{"key":"2748_CR8","doi-asserted-by":"publisher","first-page":"1854","DOI":"10.1016\/j.cgh.2022.09.032","volume":"21","author":"M Jachs","year":"2023","unstructured":"Jachs\u00a0M, Hartl\u00a0L, Simbrunner\u00a0B, et\u00a0al. The Sequential Application of Baveno VII Criteria and VITRO Score Improves Diagnosis of Clinically Significant Portal Hypertension. Clin Gastroenterol Hepatol. 2023;21:1854\u20131863.e1810.","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2748_CR9","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1016\/j.cgh.2021.07.012","volume":"20","author":"M Jachs","year":"2022","unstructured":"Jachs\u00a0M, Hartl\u00a0L, Simbrunner\u00a0B, et\u00a0al. Decreasing von Willebrand Factor Levels Upon Nonselective Beta Blocker Therapy Indicate a Decreased Risk of Further Decompensation, Acute-on-chronic Liver Failure, and Death. Clin Gastroenterol Hepatol. 2022;20:1362\u201373.","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2748_CR10","doi-asserted-by":"publisher","first-page":"2501","DOI":"10.1111\/liv.15365","volume":"42","author":"B Simbrunner","year":"2022","unstructured":"Simbrunner\u00a0B, Villesen\u00a0IF, K\u00f6nigshofer\u00a0P, et\u00a0al. Systemic inflammation is linked to liver fibrogenesis in patients with advanced chronic liver disease. Liver Int. 2022;42:2501\u201312.","journal-title":"Liver Int"}],"container-title":["Wiener klinische Wochenschrift"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00508-026-02748-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00508-026-02748-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00508-026-02748-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T14:08:51Z","timestamp":1781186931000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00508-026-02748-2"}},"subtitle":["Case reports"],"short-title":[],"issued":{"date-parts":[[2026,6,11]]},"references-count":10,"alternative-id":["2748"],"URL":"https:\/\/doi.org\/10.1007\/s00508-026-02748-2","relation":{},"ISSN":["0043-5325","1613-7671"],"issn-type":[{"value":"0043-5325","type":"print"},{"value":"1613-7671","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,11]]},"assertion":[{"value":"2 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"M.\u00a0Jachs served as a\u00a0speaker and\/or consultant for Echosens and Gilead and received grant support from Gilead. M.\u00a0Mandorfer served as a\u00a0speaker and\/or consultant and\/or advisory board member for AbbVie, Echosens, Eli Lilly, Gilead, Ipsen, Takeda, and W.\u202fL.\u00a0Gore & Associates and received travel support from AbbVie and Gilead. A.\u00a0Vaillant is employee and shareholder of Replicor Inc. T.\u00a0Reiberger is a\u00a0section editor of Wiener Klinische Wochenschrift and was recused from every editorial procedure of this submission including peer-review and academic decisions. T.\u00a0Reiberger served as a\u00a0speaker and\/or consultant and\/or advisory board member for AbbVie, Bayer, Boehringer Ingelheim, Gilead, Intercept, MSD, Siemens, and W.\u202fL.\u00a0Gore & Associates and received grants\/research support from AbbVie, Boehringer Ingelheim, Gilead, Intercept, MSD, Myr Pharmaceuticals, Pliant, Philips, Siemens, and W.\u202fL.\u00a0Gore & Associates as well as travel support from AbbVie, Boehringer Ingelheim, Gilead and Roche. M.\u00a0Schwarz has nothing to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All patients gave written informed consent to participate in the prospective, observational HEPAS registry study (Vote number 2139\/2021 by the IRB of the Medical University of Vienna). The patients received REP 2139-Mg for compassionate use owing to nonresponse to approved treatment on request by the treating physicians within the international compassionate access program (NCT05683548) [\n                      \n                      ], which did not conflict with inclusion in the HEPAS registry study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standards"}}]}}