{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:41:25Z","timestamp":1791477685536,"version":"4.3.4"},"reference-count":28,"publisher":"The Korean Association for the Study of the Liver","issue":"3","license":[{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"HighTide Therapeutics, Inc."}],"content-domain":{"domain":["e-cmh.org"],"crossmark-restriction":true},"short-container-title":["CMH"],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:p>Background\/Aims: Berberine ursodeoxycholate (HTD1801) has been shown to significantly reduce liver fat content (LFC) in an 18-week, placebo-controlled Phase 2 study in patients with metabolic dysfunction-associated steatohepatitis (MASH) and type 2 diabetes mellitus. The purpose of this assessment was to establish proof of concept in liver histologic improvement with HTD1801 treatment based on preclinical and clinical evidence.Methods: The efficacy of HTD1801 was evaluated in a preclinical MASH\/dyslipidemia model (golden hamsters fed a high fat diet, eight\/group) after six weeks of daily treatment. Additionally, in a secondary analysis of a Phase 2 clinical study, 100 patients with presumed MASH were evaluated by multiple noninvasive markers associated with MASH resolution and\/or fibrosis improvement. These include magnetic resonance imaging proton density fat fraction (MRIPDFF; \u226530% LFC reduction), iron-corrected T1 (\u226580 ms reduction), alanine aminotransferase (\u226517 U\/L reduction), weight loss (\u22655% reduction), Fibrosis-4 index (shift to &lt;1.3), and MASH resolution index (achieving \u2265\u20130.67).Results: Preclinical findings in the MASH\/dyslipidemia hamster model showed that HTD1801 significantly improved histologic fibrosis and the Nonalcoholic Fatty Liver Disease Activity Score to such a degree that improvements approximated the appearance of the normal controls. In the clinical study, 52% of HTD1801-treated patients achieved MRI response criteria compared to 24% of placebo (p&lt;0.05). Dose-dependent improvements were observed across biomarkers, with more HTD1801-treated patients achieving response criteria associated with improvements in the histologic features of MASH.Conclusions: These findings suggest that HTD1801 has strong potential to produce histological improvements in patients with MASH.<\/jats:p>","DOI":"10.3350\/cmh.2025.0145","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T21:40:20Z","timestamp":1745271620000},"page":"1071-1083","update-policy":"https:\/\/doi.org\/10.3350\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["HTD1801 demonstrates promising potential for histologic improvements in metabolic dysfunction-associated steatohepatitis in both a preclinical and phase 2 study"],"prefix":"10.3350","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2215-9410","authenticated-orcid":true,"given":"Vincent 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