Retrospective Cohort Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Feb 27, 2023; 15(2): 265-273
Published online Feb 27, 2023. doi: 10.4254/wjh.v15.i2.265
Prevalence of non-alcoholic fatty liver disease in patients with nephrotic syndrome: A population-based study
Somtochukwu Stephen Onwuzo, Asif Ali Hitawala, Antoine Boustany, Prabhat Kumar, Ashraf Almomani, Chidera Onwuzo, Jessy Mascarenhas Monteiro, Imad Asaad
Somtochukwu Stephen Onwuzo, Asif Ali Hitawala, Antoine Boustany, Prabhat Kumar, Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44111, United States
Ashraf Almomani, Digestive Disease and Hepatology, Cleveland Clinic Foundation Florida, Weston, FI 33331, United States
Chidera Onwuzo, Department of Medicine & Surgery, General Hospital Lagos Island, Lagos Island 101223, Lagos, Nigeria
Jessy Mascarenhas Monteiro, Department of Medicine, Ross University School of Medicine, Bridgetown B11093, St Michael, Barbados
Imad Asaad, Digestive Disease and Hepatology, Cleveland Clinic Foundation, Cleveland, OH 44111, United States
Author contributions: Onwuzo S designed the research study; Hitawala A and Boustany A performed the biostatistical analysis; Boustany A and Kumar P carried out the data collection; Onwuzo S, Hitawala A, Onwuzo C, Almomani A, Monteiro J, and Asaad I contributed to the manuscript writing, editing and scientific review; All authors have read and agree to the submitted version of the manuscript.
Institutional review board statement: Our cohort’s data were obtained using a validated, multicentered and daily-updated database called Explorys (Explorys Inc, Cleveland, OH, United States). Explorys does not record individual patient data such as name, laboratory or imaging results. Patient’s informed consent and approval of Institutional Review Board are not required since Explorys is a Health Insurance Portability and Accountability Act (HIPAA)-compliant platform.
Informed consent statement: Consent was not obtained but the presented data are anonymized without any risk of identification.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at onwuzos@ccf.org. Consent was not obtained but the presented data are anonymized without any risk of identification.
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: Somtochukwu Stephen Onwuzo, MD, Doctor, Internal Medicine, Cleveland Clinic Foundation, 18101 Lorain Road, Cleveland, OH 44111, United States. onwuzos@ccf.org
Received: December 6, 2022
Peer-review started: December 6, 2022
First decision: January 11, 2023
Revised: January 21, 2023
Accepted: February 8, 2023
Article in press: February 8, 2023
Published online: February 27, 2023
Processing time: 79 Days and 23.7 Hours
Abstract
BACKGROUND

Non-alcoholic fatty liver disease (NAFLD) is a global health concern with a prevalence of about 25% amongst United States adults. Its increased prevalence is attributed to increase in patients with obesity and metabolic syndrome, partly due to similar mechanisms of injury. Nephrotic syndrome (NS) is a clinical entity resulting from extensive proteinuria leading to hypoalbuminemia, hyperlipidemia, edema, and other complications. Given its association with hyperlipidemia, there is concern that patients with NS may be at increased risk of NAFLD.

AIM

To perform a cross-sectional population-based study to investigate the prevalence and risk factors of NAFLD in patients with NS.

METHODS

A large multicenter database (Explorys Inc., Cleveland, OH, United States) was utilized for this retrospective cohort study. A cohort of 49700 patients with a diagnosis of “Non-Alcoholic fatty liver disease” using the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) between 1999-2022 was identified. Inclusion criteria were age ≥ 18 years, presence of NAFLD, presence of NS. There were no specific exclusion criteria. Univariate and multivariate analysis were performed to adjust for multiple risk factors including age, gender, Caucasian race, NS, type II diabetes mellitus, hypothyroidism, dyslipidemia, obesity, metabolic syndrome and chronic kidney disease. Statistical analysis was conducted using R, and for all analyses, a 2-sided P value of < 0.05 was considered statistically significant.

RESULTS

Among the 78734750 individuals screened in this database, there were a total of 49700 subjects with NAFLD. In univariate analysis, the odds of having NAFLD in patients with NS, type 2 diabetes mellitus, hypothyroidism, dyslipidemia, obesity, metabolic syndrome and chronic kidney disease were 14.84 [95% confidence interval (95%CI) 13.67-16.10], 17.05 (95%CI 16.78-17.32), 6.99 (95%CI 6.87-7.11), 13.61 (95%CI 13.38-13.84), 19.19 (95%CI 18.89-19.50), 29.09 (95%CI 28.26--29.95), and 9.05 (95%CI 8.88-9.22), respectively. In multivariate analysis, the odds of having NAFLD amongst patients with NS were increased to 1.85 (95%Cl 1.70-2.02), while the odds were also remained high in patients that have type 2 diabetes mellitus [odds ratio (OR) 3.84], hypothyroidism (OR 1.57), obesity (OR 5.10), hyperlipidemia (OR 3.09), metabolic syndrome (OR 3.42) and chronic kidney disease (OR 1.33).

CONCLUSION

Patients with NS are frequently found to have NAFLD, even when adjusting for common risk factors. Hence, clinicians should maintain a high index of suspicion regarding presence of NAFLD in patients with NS.

Keywords: Non-alcoholic fatty liver disease; Nephrotic syndrome; Chronic kidney disease; Hyperlipidemia; Population-based study; Database

Core Tip: We conducted a population-based study to investigate the prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with Nephrotic syndrome. We screened over 78 million individuals in a nationwide multicenter database. We performed a comprehensive multivariate analysis accounting for multiple cofounding factors including age ≥ 65 years, gender, Caucasian race, obesity, diabetes mellitus type 2, metabolic syndrome, dyslipidemia, chronic kidney disease and hypothyroidism. We found that patients with nephrotic syndrome had a higher prevalence of NAFLD. However, we could not account for certain confounders such as elevated uric acid levels, hormonal therapy, chemotherapy for tumors, and certain drugs such as corticosteroids, which are known to be risk factors for NAFLD. Further studies are required to confirm these findings and assess the utility of surveillance strategies for NAFLD in patients with nephrotic syndrome.