Retrospective Cohort Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jul 27, 2022; 14(7): 1398-1407
Published online Jul 27, 2022. doi: 10.4254/wjh.v14.i7.1398
Cardiac risk factors limiting survival to liver transplantation in patients with nonalcoholic fatty liver disease
Michael Delicce, Joseph Mauch, Abel Joseph, Ruishen Lyu, Heather Kren, Rose Bartow, Donna Ferchill, Maan Fares, Jamile Wakim-Fleming
Michael Delicce, Abel Joseph, Department of Internal Medicine, Cleveland Clinic, Cleveland, OH 44195, United States
Joseph Mauch, Lerner College of Medicine at Case Western Reserve University, Cleveland Clinic, Cleveland, OH 44195, United States
Ruishen Lyu, Heather Kren, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH 44195, United States
Rose Bartow, Donna Ferchill, Department of Liver Transplantation, Cleveland Clinic, Cleveland, OH 44195, United States
Maan Fares, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH 44195, United States
Jamile Wakim-Fleming, Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, OH 44195, United States
Author contributions: Delicce M, Wakim-Fleming J, Lyu R and Fares M designed the research study; Delicce M, Mauch J, Joseph A, Lyu R, Bartow R, Ferchill D and Kren H performed the research; Lyu R performed statistical analysis; Delicce M, Mauch J and Lyu R analyzed the data and wrote the manuscript; all authors have read and approve the final manuscript.
Institutional review board statement: This study was reviewed and approved by the Cleveland Clinic Institutional Review Board [IRB#21-372].
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All authors have no conflicts of interest to disclose.
Data sharing statement: The consent was not obtained but the presented data are anonymized and risk of identification is low.
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: Michael Delicce, MD, Doctor, Department of Internal Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, United States. deliccm@ccf.org
Received: April 5, 2022
Peer-review started: April 5, 2022
First decision: April 28, 2022
Revised: May 10, 2022
Accepted: June 22, 2022
Article in press: June 22, 2022
Published online: July 27, 2022
Processing time: 112 Days and 17.2 Hours
Abstract
BACKGROUND

Nonalcoholic fatty liver disease (NAFLD) describes the hepatic manifestations of metabolic syndrome, which is estimated to affect 25% of adults, and currently represents the second most common indication for liver transplant in the United States. Studies have shown that patients with NAFLD are at an increased risk for heart failure, arrhythmia, and coronary artery disease (CAD), which may impact outcomes of liver transplantation. However, it remains unclear whether the presence of cardiac disease affects survival prior to liver transplant. If so, this would represent an important opportunity to optimize cardiac status and improve outcomes before liver transplant.

AIM

To identify cardiac factors that impact survival to liver transplantation in patients with NAFLD and on the transplant waitlist.

METHODS

The aim of this study was to identify cardiac risk factors that limit survival to transplant in patients with NAFLD. We performed a retrospective analysis of patients with NAFLD listed for liver transplant at a tertiary academic medical center in the United States from January 2015 to January 2021, identified through United Network of Organ Sharing registry. Exclusion criteria included a concurrent etiology of liver disease and removal from the transplant list due to chemical dependency, lack of social support, improvement in liver disease, or being lost to follow-up. We manually reviewed patient charts including electrocardiogram, echocardiogram, and cardiac catheterization reports as well as physician notes to identify cardiac disease states (i.e., heart failure, arrhythmia, valvular disease and CAD) and other related diagnoses. We performed a survival analysis by Cox proportional hazards regression model to analyze the association between cardiac factors at the time listed for transplant and death or clinical deterioration prior to transplant.

RESULTS

Between January 2015 and January 2021, 265 patients with nonalcoholic fatty liver disease were listed for liver transplant at our institution. Our patient sample had a median age of 63 and an even distribution between sexes. The median Model for End-Stage Liver Disease (MELD) score was 17 and the median body mass index was 31.6. Of these 265 patients, 197 (74.3%) survived to transplant and 68 (25.7%) died or clinically deteriorated prior to transplant. The presence of mild or moderate CAD represented a hazard ratio of 2.013 (95%CI 1.078-3.759, P = 0.029) for death or clinical deterioration when compared to patients without CAD, after adjustment for age, sex, and MELD. MELD represented an adjusted hazard ratio of 1.188.

CONCLUSION

Mild or moderate CAD represents a hazard for waitlist mortality prior to liver transplant in patients with NAFLD. Aggressive management of CAD may be needed to improve patient outcomes.

Keywords: Nonalcoholic fatty liver disease; Liver transplant; Cardiovascular disease; Pre-transplant outcomes; Coronary artery disease; Risk factors

Core Tip: Nonalcoholic fatty liver disease (NAFLD) continues to rise in prevalence as a leading indication for liver transplantation. Due to its metabolic features, NAFLD is a risk factor for cardiovascular disease such as coronary artery disease (CAD), atrial fibrillation and heart failure. In our study, we examined the impact of cardiac factors on survival to liver transplant, once listed, in patients with NAFLD. We observed that even mild or moderate CAD represents an independent hazard for waitlist mortality before liver transplant after adjustment for confounding variables. This compels improved treatment of less severe forms of CAD in patients undergoing liver transplant.