Prospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 27, 2021; 13(12): 2179-2191
Published online Dec 27, 2021. doi: 10.4254/wjh.v13.i12.2179
Non-alcoholic steatohepatitis in liver transplant recipients diagnosed by serum cytokeratin 18 and transient elastography: A prospective study
Alshaima Alhinai, Afsheen Qayyum-Khan, Xun Zhang, Patrick Samaha, Peter Metrakos, Marc Deschenes, Philip Wong, Peter Ghali, Tian-Yan Chen, Giada Sebastiani
Alshaima Alhinai, Experimental Medicine, McGill University, Montreal H4A3J1, Canada
Afsheen Qayyum-Khan, Patrick Samaha, Marc Deschenes, Philip Wong, Tian-Yan Chen, Giada Sebastiani, Medicine, McGill University Health Centre, Montreal H4A3J1, Canada
Xun Zhang, Departments of Pediatrics and Epidemiology, McGill University, Montreal H4A3J1, Canada
Peter Metrakos, Cancer Research Program, The Research Institute of McGill University and The Research Institute of McGill University Health Center, Montreal H4A3J1, Canada
Peter Ghali, Medicine, University of Florida, Jacksonville, Florida 32218, United States
Author contributions: Alhinai A and Sebastiani G contributed to study design and first draft of the article; Alhinai A, Qayyum-Khan A, Samaha P, Metrakos P, Deschenes M, Wong P, Ghali P, Chen TY and Sebastiani G contributed to data and interpretation of data; Zhang X contributed to statistical analysis; Sebastiani G contributed to conception and statistical analysis; and all authors approved the final version of the article.
Supported by the Canadian Donation and Transplantation Research Program of the Canadian Society of Transplantation (grant competition 2014); Sebastiani G is supported by a Senior Salary Award from Fonds de la Recherche en Santé du Quebéc (FRQS) (No. #296306).
Institutional review board statement: The study was approved by the Research Ethics Board of the Research Institute of MUHC (code 15-002-MUHC). The study was conducted according to the Declaration of Helsinki and Good Clinical Practice guidelines.
Clinical trial registration statement: The study was registered at ClinicalTrials.gov (NCT03128918).
Informed consent statement: All patients provided their informed written consent prior to participation.
Conflict-of-interest statement: Deschenes M has served as an advisory board member for Merck, Janssen, Gilead; Wong P has acted as consultant for BMS, Gilead, Merck, Novartis; Sebastiani G has acted as speaker for Pfizer, Merck, Novonordisk, Novartis, Gilead and AbbVie, served as an advisory board member for Merck, Gilead, Pfizer, Allergan, Novonordisk, Intercept and Novartis and has received research funding from Merck and Theratec. All other authors have no conflicts of interest to declare.
Data sharing statement: According to stipulations of the patient consent form signed by all study participants, ethical restrictions imposed by our Institutional Ethics review boards (Institutional Ethics Review Board Biomedical B Research Ethics Board of the McGill University Health Centre), and legal restrictions imposed by Canadian law regarding clinical trials, anonymized data are available upon request. Please send data access requests to Sheldon Levy, Biomedical B (BMB) Research Ethics Board (REB) Coordinator Centre for Applied Ethics, 5100, boul. de Maisonneuve Ouest, 5th floor, Office 576, Montréal, Québec, H4A 3T2, Canada.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Giada Sebastiani, MD, Associate Professor, Medicine, McGill University Health Centre, 1001 boulevard Decarie, Montreal H4A3J1, Canada. giada.sebastiani@mcgill.ca
Received: July 1, 2021
Peer-review started: July 1, 2021
First decision: July 13, 2021
Revised: July 25, 2021
Accepted: November 14, 2021
Article in press: November 14, 2021
Published online: December 27, 2021
Processing time: 178 Days and 16 Hours
Abstract
BACKGROUND

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) seem common after liver transplantation.

AIM

To investigate incidence and predictors of NAFLD and NASH by employing noninvasive testing in liver transplant recipients, namely controlled attenuation parameter (CAP) and the serum biomarker cytokeratin 18 (CK-18). We also evaluated the diagnostic accuracy of CK-18 and CAP compared to liver histology.

METHODS

We prospectively recruited consecutive adult patients who received liver transplant at the McGill University Health Centre between 2015-2018. Serial measurements of CK-18 and CAP were recorded. NAFLD and NASH were diagnosed by CAP ≥ 270 dB/m, and a combination of CAP ≥ 270 dB/m with CK-18 > 130.5 U/L, respectively. Incidences and predictors of NAFLD and NASH were investigated using survival analysis and Cox proportional hazards.

RESULTS

Overall, 40 liver transplant recipients (mean age 57 years; 70% males) were included. During a median follow-up of 16.8 mo (interquartile range 15.6-18.0), 63.0% and 48.5% of patients developed NAFLD and NASH, respectively. On multivariable analysis, after adjusting for sex and alanine aminotransferase, body mass index was an independent predictor of development of NAFLD [adjusted hazard ratio (aHR): 1.21, 95% confidence interval (CI): 1.04-1.41; P = 0.01] and NASH (aHR: 1.26, 95%CI: 1.06-1.49; P < 0.01). Compared to liver histology, CAP had a 76% accuracy to diagnose NAFLD, while the accuracy of CAP plus CK-18 to diagnose NASH was 82%.

CONCLUSION

NAFLD and NASH diagnosed non-invasively are frequent in liver transplant recipients within the first 18 mo. Close follow-up and nutritional counselling should be planned in overweight patients.

Keywords: Nonalcoholic steatohepatitis; Nonalcoholic fatty liver disease; Controlled attenuation parameter; Cytokeratin 18; Overweight; Accuracy

Core Tip: This is the first prospective study using cytokeratin 18 in association with transient elastography with controlled association parameter to investigate nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) in liver transplant recipients. NAFLD and NASH diagnosed by non-invasive tests occur frequently in the first 18 mo from liver transplant. Overweight is the main risk factor. Non-invasive liver fibrosis markers have suboptimal accuracy.