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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Divergent trajectories of lean vs obese non-alcoholic steatohepatitis patients from listing to post-transplant: A retrospective cohort study
Fakhar Ali Qazi-Arisar, Raj Uchila, Catherine Chen, Cathy Yang, Shi-Yi Chen, Ravikiran Sindhuvalada Karnam, Amirhossein Azhie, Wei Xu, Zita Galvin, Nazia Selzner, Leslie Lilly, Mamatha Bhat
Fakhar Ali Qazi-Arisar, Raj Uchila, Catherine Chen, Cathy Yang, Ravikiran Sindhuvalada Karnam, Amirhossein Azhie, Zita Galvin, Nazia Selzner, Leslie Lilly, Mamatha Bhat, Ajmera Transplant Program, Toronto General Hospital, University Health Network, Toronto M5G 2N2, Ontario, Canada
Fakhar Ali Qazi-Arisar, Raj Uchila, Ravikiran Sindhuvalada Karnam, Zita Galvin, Nazia Selzner, Leslie Lilly, Mamatha Bhat, Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto M5G 2N2, Ontario, Canada
Fakhar Ali Qazi-Arisar, National Institute of Liver and GI Diseases, Dow University of Health Sciences, Karachi 75330, Pakistan
Shi-Yi Chen, Wei Xu, Department of Biostatistics, Princess Margaret Cancer Center, University Health Network, Toronto M5G 2C1, Ontario, Canada
Wei Xu, Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto M5G 2C1, Ontario, Canada
Author contributions: Qazi-Arisar FA and Uchila R given their equal contribution in the manuscript; Bhat M was the guarantor and designed the study; Qazi-Arisar FA, Uchila R, Chen C, Yang C, Chen SY, Karnam RS and Azhie A participated in the acquisition, analysis, and interpretation of the data, and drafted the initial manuscript; Qazi-Arisar FA, Xu W, Galvin Z, Selzner N, Lilly L and Bhat M revised the article critically for important intellectual content.
Institutional review board statement: The study was reviewed and approved by the Research Ethics board of the University Health Network (Toronto, Canada).
Informed consent statement: Given retrospective nature of study from chart review, written informed consent was not required.
Conflict-of-interest statement: Dr. Bhat reports other from Novo Nordisk, other from Ipsen, grants from Paladin, grants from Natera, grants from Oncoustics, grants from MedoAI, grants from Lallemand, personal fees from Novartis, personal fees from Lupin, outside the submitted work.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
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: Mamatha Bhat, FRCP (C), MD, PhD, Assistant Professor, Ajmera Transplant Program, Toronto General Hospital, University Health Network, 585 University Ave, 11th Floor, Room 183, Toronto M5G 2N2, Ontario, Canada. mbhat33@gmail.com
Received: February 3, 2022
Peer-review started: February 3, 2022
First decision: April 10, 2022
Revised: April 22, 2022
Accepted: June 15, 2022
Article in press: June 15, 2022
Published online: July 14, 2022
ARTICLE HIGHLIGHTS
Research background
Non-alcoholic steatohepatitis (NASH) cirrhosis is the second leading indication for liver transplantation (LT). There is a conflicted role of body mass index (BMI) on outcomes of NASH cirrhosis while on waitlist and post liver transplant.
Research motivation
There are few reports on the waitlist and post liver transplant outcomes of lean vs obese NASH patients, and the impact of ascites adjusted BMI have not been fully clarified.
Research objectives
The objective of this study was to compare the longitudinal trajectories of patients with lean vs obese NASH cirrhosis, from listing up to post-transplant, having adjusted their BMI for ascites.
Research methods
A retrospective analysis of all adult NASH patients listed for LT at the University Health Network, Toronto between November 2012 and May 2019 was performed. We summarized the clinical characteristics of patients with lean and obese NASH. Competing risk analyses and Cox Proportional Hazard models were used to assess the cumulative incidence of transplant and survival outcomes.
Research results
Out of 265 patients listed for NASH cirrhosis, 176 were included. The median age was 61 (32–71.4) years; 46% were females. 111 patients underwent LT. Lean NASH patients were elderly at time of listing (median age 61.6 years vs 60.3 years, P = 0.048), worse renal functions at end of listing (median estimated glomerular filtration 48 mL/min/1.73 m2 vs 57 mL/min/1.73 m2, P = 0.017), carried more severe ascites (66.6% vs 45%, P = 0.03) and were more paracentesis dependent (72.2% vs 52.9%, P = 0.016). Obese robust patients had better waitlist survival [hazard ratio (HR): 0.12; 95%CI: 0.05–0.29, P < 0.0001] with higher instantaneous rate of transplant (HR: 5.71; 95%CI: 1.26–25.9, P = 0.02). Lean NASH patients had a substantially higher risk of graft loss within 90 d post-LT (1.2% vs 13.8%, P = 0.032) and death post-LT (2.4% vs 17.2%, P = 0.029). 1- 3- and 5-year graft survival was poor for lean NASH (78.6%, 77.3% and 41.7% vs 98.6%, 96% and 85% respectively). Overall patient survival post-LT was significantly worse in lean NASH (HR: 0.17; 95%CI: 0.03–0.86, P = 0.0142) with 83% lower instantaneous rate of death in obese group. Post-transplant renal function was significantly better in lean NASH patients at 5 years (median creatinine 111 μmol/L vs 153.5 μmol/L, P = 0.019).
Research conclusions
Although lean NASH was thought to be more benign than obese NASH, our study suggests a paradoxical correlation of lean NASH with waitlist outcomes, and graft and patient survival post-LT, in conjunction with often comorbid frailty.
Research perspectives
To understand the underlying molecular mechanisms linking lean NASH with worse outcomes, there is need of identifying the factors such as genetic variants, body fat distribution/visceral adiposity, which can play role in this paradox.
