Malakar S, Sood N, Giri S, Samanta A. Nor-ursodeoxycholic acid in hepatobiliary diseases: A narrative review. World J Gastrointest Pharmacol Ther 2026; 17(3): 120122 [DOI: 10.4292/wjgpt.120122]
Corresponding Author of This Article
Sayan Malakar, Assistant Professor, Department of Hepatology and Liver Transplantation, Punjab Institute of Liver and Biliary Sciences, 1210 Sector 77, Mohali 160059, Punjab, India. oneandonlydrsayan@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
review-article
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Sayan Malakar, Department of Hepatology and Liver Transplantation, Punjab Institute of Liver and Biliary Sciences, Mohali 160059, Punjab, India
Neha Sood, Department of Internal Medicine, Post Graduate Institution of Medical Education and Research, Chandigarh 160012, India
Suprabhat Giri, Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar 751024, Odisha, India
Arghya Samanta, Department of Pediatric Gastroenterology, Institute of Post Graduate Medical Education and Research, Kolkata 700020, West Bengal, India
Author contributions: Malakar S has conceptualised and designed the manuscript; Malakar S and Sood N drafted the initial manuscript; Malakar S, Sood N, Giri S, and Samanta A contributed to the literature review, analysis, data collection, interpretation, critical revision of the initial manuscript, and approved the final version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Sayan Malakar, Assistant Professor, Department of Hepatology and Liver Transplantation, Punjab Institute of Liver and Biliary Sciences, 1210 Sector 77, Mohali 160059, Punjab, India. oneandonlydrsayan@gmail.com
Received: February 24, 2026 Revised: April 9, 2026 Accepted: May 29, 2026 Published online: September 5, 2026 Processing time: 193 Days and 15.7 Hours
Abstract
Nor-ursodeoxycholic acid (nor-UDCA) is a side-chain shortened analogue of ursodeoxycholic acid (UDCA). Because of its biochemical modification, it is resistant to amidation. Nor-UDCA undergoes cholehepatic shunt, leading to increased bicarbonate secretion. In addition, it has shown potential antifibrotic activity in the animal model of cholestasis and fibrosis. Nor-UDCA has several advantages over UDCA in its pharmacokinetic and pharmacodynamic properties. However, its safety and efficacy data on cholestatic diseases are largely extrapolated from pre-clinical animal studies. Vitamin E, resmetirom, peroxisome proliferator-activated receptor agonists, and incretin-based therapies dominate the pharmacotherapeutic armamentarium for metabolic dysfunction-associated steatotic liver disease or steatohepatitis. Recently, nor-UDCA has been evaluated in patients with metabolic dysfunction-associated steatotic liver disease with conflicting therapeutic benefits and a controversial trial endpoint. This comprehensive narrative review focuses on its novel mechanism of action, comparison with UDCA, and underscores the limited evidence of its safety and efficacy in various hepatobiliary diseases. This review also discusses future research prospects of nor-UDCA in hepato-biliary diseases, which addresses the research gap in existing literature.
Core Tip: Nor-ursodeoxycholic acid or norucholic acid is a short-chain shortened derivative of ursodeoxycholic acid. Pre-clinical animal studies have revealed conflicting results. Clinical data on primary cholestatic liver diseases and metabolic dysfunction-associated liver diseases are also limited. This narrative review comprehensively explores the mechanism of action and discusses the pharmacokinetics and pharmacodynamic differences with ursodeoxycholic acid. It also addresses the potential gap in the literature regarding the role of nor-ursodeoxycholic acid in metabolic dysfunction-associated liver diseases and primary sclerosing cholangitis based on primitive data.
