{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:44:51Z","timestamp":1792457091785,"version":"4.5.0"},"reference-count":277,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Chronic hepatobiliary damage progressively leads to fibrosis, which may evolve into cirrhosis and\/or hepatocellular carcinoma. The fight against the increasing incidence of liver-related morbidity and mortality is challenged by a lack of clinically validated early-stage biomarkers and the limited availability of effective anti-fibrotic therapies. Current research is focused on uncovering the pathogenetic mechanisms that drive liver fibrosis. Drugs targeting molecular pathways involved in chronic hepatobiliary diseases, such as inflammation, hepatic stellate cell activation and proliferation, and extracellular matrix production, are being developed. Etiology-specific treatments, such as those for hepatitis B and C viruses, are already in clinical use, and efforts to develop new, targeted therapies for other chronic hepatobiliary diseases are ongoing. In this review, we highlight the major molecular changes occurring in patients affected by metabolic dysfunction-associated steatotic liver disease, viral hepatitis (Delta virus), and autoimmune chronic liver diseases (autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis). Further, we describe how this knowledge is linked to current molecular therapies as well as ongoing preclinical and clinical research on novel targeting strategies, including nucleic acid-, mesenchymal stromal\/stem cell-, and extracellular vesicle-based options. Much clinical development is obviously still missing, but the plethora of promising potential treatment strategies in chronic hepatobiliary diseases holds promise for a future reversal of the current increase in morbidity and mortality in this group of patients.<\/jats:p>","DOI":"10.3390\/biom15010121","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T06:13:07Z","timestamp":1736835187000},"page":"121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Current Treatment Regimens and Promising Molecular Therapies for Chronic Hepatobiliary Diseases"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2450-5911","authenticated-orcid":false,"given":"Marilena","family":"Durazzo","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, University of Turin, C.so A.M. Dogliotti 14, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Ferro","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, C.so A.M. Dogliotti 14, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7629-1199","authenticated-orcid":false,"given":"Victor Manuel","family":"Navarro-Tableros","sequence":"additional","affiliation":[{"name":"2i3T, Societ\u00e0 per la Gestione dell\u2019Incubatore di Imprese e per il Trasferimento Tecnologico, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2928-7067","authenticated-orcid":false,"given":"Andrea","family":"Gaido","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, C.so A.M. Dogliotti 14, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Fornengo","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, C.so A.M. Dogliotti 14, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6238-1860","authenticated-orcid":false,"given":"Fiorella","family":"Altruda","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Centre \u201cGuido Tarone\u201d, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8340-8885","authenticated-orcid":false,"given":"Renato","family":"Romagnoli","sequence":"additional","affiliation":[{"name":"General Surgery 2U-Liver Transplant Unit, Department of Surgical Sciences, Azienda Ospedaliero Universitaria Citt\u00e0 della Salute e della Scienza di Torino, University of Turin, Corso Bramante 88-90, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren K.","family":"Moestrup","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"},{"name":"Department of Clinical Biochemistry, Aarhus University Hospital, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Luigi","family":"Calvo","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology Unit, Regina Margherita Children\u2019s Hospital, Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6070-6716","authenticated-orcid":false,"given":"Sharmila","family":"Fagoonee","sequence":"additional","affiliation":[{"name":"Institute for Biostructure and Bioimaging, National Research Council, Molecular Biotechnology Centre \u201cGuido Tarone\u201d, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jhep.2023.03.017","article-title":"Global burden of liver disease: 2023 update","volume":"79","author":"Devarbhavi","year":"2023","journal-title":"J. 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