Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2020; 26(21): 2740-2757
Published online Jun 7, 2020. doi: 10.3748/wjg.v26.i21.2740
Post-transplant diabetes mellitus and preexisting liver disease - a bidirectional relationship affecting treatment and management
Maja Cigrovski Berkovic, Lucija Virovic-Jukic, Ines Bilic-Curcic, Anna Mrzljak
Maja Cigrovski Berkovic, Department of Kinesiological Anthropology and Methodology, Faculty of Kinesiology, University of Zagreb, Zagreb 10000, Croatia
Maja Cigrovski Berkovic, Clinical Hospital Dubrava, Zagreb 10000, Croatia
Maja Cigrovski Berkovic, Ines Bilic-Curcic, Department of Pharmacology, Faculty of Medicine, University of J. J. Strossmayer Osijek, Osijek 31000, Croatia
Lucija Virovic-Jukic, Ines Bilic-Curcic, Anna Mrzljak, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
Lucija Virovic-Jukic, Department of Medicine, Division of Gastroenterology and Hepatology, Sisters of Charity University Hospital, Zagreb 10000, Croatia
Ines Bilic-Curcic, Clinical Hospital Center Osijek, Osijek 31000, Croatia
Anna Mrzljak, Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
Author contributions: Cigrovski Berkovic M made contributions to the conception and design of the study, involved in drafting and revising the manuscript critically; Virovic-Jukic L, Bilic-Curic I and Mrzljak A were involved in collecting data, drafting and writing the manuscript; all authors read and approved the final manuscript.
Conflict-of-interest statement: No potential conflicts of interest.
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:
Corresponding author: Anna Mrzljak, MD, PhD, FEBGH, Associate Professor, School of Medicine, University of Zagreb, Salata 3b, Zagreb 10000, Croatia.
Received: February 22, 2020
Peer-review started: February 22, 2020
First decision: April 12, 2020
Revised: April 24, 2020
Accepted: May 14, 2020
Article in press: May 14, 2020
Published online: June 7, 2020

Liver cirrhosis and diabetes mellitus (DM) are both common conditions with significant socioeconomic burden and impact on morbidity and mortality. A bidirectional relationship exists between DM and liver cirrhosis regarding both etiology and disease-related complications. Type 2 DM (T2DM) is a well-recognized risk factor for chronic liver disease and vice-versa, DM may develop as a complication of cirrhosis, irrespective of its etiology. Liver transplantation (LT) represents an important treatment option for patients with end-stage liver disease due to non-alcoholic fatty liver disease (NAFLD), which represents a hepatic manifestation of metabolic syndrome and a common complication of T2DM. The metabolic risk factors including immunosuppressive drugs, can contribute to persistent or de novo development of DM and NAFLD after LT. T2DM, obesity, cardiovascular morbidities and renal impairment, frequently associated with metabolic syndrome and NAFLD, may have negative impact on short and long-term outcomes following LT. The treatment of DM in the context of chronic liver disease and post-transplant is challenging, but new emerging therapies such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) targeting multiple mechanisms in the shared pathophysiology of disorders such as oxidative stress and chronic inflammation are a promising tool in future patient management.

Keywords: Diabetes mellitus, Liver transplantation, Non-alcoholic fatty liver disease, Metabolic syndrome, Insulin-resistance, Glucagon-like peptide-1 receptor agonists, Sodium–glucose cotransporter 2 inhibitors

Core tip: This review explores complex relationships and mechanisms involved in the interplay between diabetes mellitus and liver disease before and after liver transplantation, especially in the term of non-alcoholic fatty liver disease, which then relate to management issues, newer treatment options and patient outcomes.