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Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2022; 28(14): 1430-1443
Published online Apr 14, 2022. doi: 10.3748/wjg.v28.i14.1430
Osteosarcopenia in autoimmune cholestatic liver diseases: Causes, management, and challenges
Nicola Pugliese, Ivan Arcari, Alessio Aghemo, Andrea G Lania, Ana Lleo, Gherardo Mazziotti
Nicola Pugliese, Ivan Arcari, Alessio Aghemo, Andrea G Lania, Ana Lleo, Gherardo Mazziotti, Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
Nicola Pugliese, Ivan Arcari, Alessio Aghemo, Ana Lleo, Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
Andrea G Lania, Gherardo Mazziotti, Department of Endocrinology, Diabetology and Medical Andrology Unit, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
Author contributions: Pugliese N, Arcari I, Lleo A, and Mazziotti G made substantial contributions to conception and design of the study, acquisition, analysis, and interpretation of the data, drafting the article, making critical revisions related to important intellectual content of the manuscript, and final approval of the version of the article to be published; Aghemo A and Lania AG made substantial contributions to conception and design of the study, making critical revisions related to important intellectual content of the manuscript, and final approval of the version of the article to be published.
Conflict-of-interest statement: AA has served as a speaker, consultant, and advisory board member for Gilead, MSD, Abbvie, Mylan, Intercept, and Alfasigma and has received research funding from Gilead and Abbvie. AL reports receiving consulting fees from Intercept Pharma, AlfaSigma, AbbVie, Gilead, and MSD and travel expenses from Intercept Pharma, AlfaSigma, and AbbVie. GM received consultant fees from Eli Lilly, Ipsen, and Novartis and lecture fees from Abiogen and Amgen.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ana Lleo, MD, PhD, Professor, Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele 20090, Milan, Italy. ana.lleo@humanitas.it
Received: September 9, 2021
Peer-review started: September 9, 2021
First decision: November 21, 2021
Revised: December 5, 2021
Accepted: March 7, 2022
Article in press: March 7, 2022
Published online: April 14, 2022
Abstract

Primary biliary cholangitis and primary sclerosing cholangitis (PSC) are the most common cholestatic liver diseases (CLD) in adults and are both characterized by an immune pathogenesis. While primary biliary cholangitis is a model autoimmune disease, with over 90% of patients presenting very specific autoantibodies against mitochondrial antigens, PSC is considered an immune mediated disease. Osteoporosis is the most common bone disease in CLD, resulting in frequent fractures and leading to significant morbidity. Further, sarcopenia is emerging as a frequent complication of chronic liver diseases with a significant prognostic impact and severe implications on the quality of life of patients. The mechanisms underlying osteoporosis and sarcopenia in CLD are still largely unknown and the association between these clinical conditions remains to be dissected. Although timely diagnosis, prevention, and management of osteosarcopenia are crucial to limit the consequences, there are no specific guidelines for management of osteoporosis and sarcopenia in patients with CLD. International guidelines recommend screening for bone disease at the time of diagnosis of CLD. However, the optimal monitoring strategies and treatments have not been defined yet and vary among centers. We herein aim to comprehensively outline the pathogenic mechanisms and clinical implications of osteosarcopenia in CLD, and to summarize expert recommendations for appropriate diagnostic and therapeutic approaches.

Keywords: Cholestatic liver diseases, Primary biliary cholangitis, Primary sclerosing cholangitis, Osteoporosis, Sarcopenia

Core Tip: Cholestatic liver diseases (CLD) in adults are characterized by an immune pathogenesis. Osteoporosis is the most common bone disease in CLD, resulting in frequent fractures and leading to significant morbidity. Sarcopenia is emerging as a frequent complication with a significant prognostic impact and severe implications on the quality of life of patients. The lack of useful preventive measures and efficacious treatment strategies remains one of the largest challenges in the management of patients with CLD.