Case Control Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 27, 2022; 14(3): 551-558
Published online Mar 27, 2022. doi: 10.4254/wjh.v14.i3.551
Prevalence of hypothyroidism and effect of thyroid hormone replacement therapy in patients with non-alcoholic fatty liver disease: A population-based study
Ashraf Almomani, Asif Ali Hitawala, Prabhat Kumar, Sura Alqaisi, Dana Alshaikh, Motasem Alkhayyat, Imad Asaad
Ashraf Almomani, Prabhat Kumar, Sura Alqaisi, Motasem Alkhayyat, Department ofInternal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44111, United States
Asif Ali Hitawala, Liver Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health, Bethesda, MD 20892, United States
Dana Alshaikh, Mutah University, Amman 00962, Jordan
Imad Asaad, Department of Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, United States
Author contributions: Almomani A and Kumar P wrote the manuscript; Hitawala AA designed the study; Alkhayyat M performed the statistical analysis; Alqaisi S, Alshaikh D collected the data; Asaad I is the corresponding author.
Institutional review board statement: No Institutional Review Board approval was required for this study since the database is de-identified.
Conflict-of-interest statement: No conflict of interest.
Data sharing statement: No additional data are available.
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: Imad Asaad, MD, Staff Physician, Department of Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, United States. asaadi@ccf.org
Received: August 16, 2021
Peer-review started: August 16, 2021
First decision: November 11, 2021
Revised: November 13, 2021
Accepted: February 24, 2022
Article in press: February 24, 2022
Published online: March 27, 2022
Processing time: 219 Days and 21.2 Hours
Abstract
BACKGROUND

Non-alcoholic fatty liver disease (NAFLD) is currently considered as the most common cause of chronic liver disease worldwide. Risk factors for NAFLD have been well-described, including obesity, type 2 diabetes mellites (T2DM), dyslipidemia (DLP) and metabolic syndrome. Hypothyroidism has been identified as an independent risk factor for the development of NAFLD, although the literature is inconsistent

AIM

To evaluate the prevalence of hypothyroidism in patients with NAFLD, assess if it is an independent risk factor and explore the effect of thyroxine replacement therapy.

METHODS

Our cohort’s data was obtained using a validated, large, multicenter database (Explorys Inc, Cleveland, OH, United States) aggregated from pooled outpatient and inpatient records of 26 different healthcare systems, consisting of a total of 360 hospitals in the United States, and utilizing Systematized Nomenclature of Medicine-Clinical Terms for coding. We evaluated a cohort of patients with hypothyroidism and NAFLD. Multivariate analysis was performed to adjust for confounding risk factors including hypertension (HTN), T2DM, DLP, obesity and metabolic syndrome. SPSS version 25, IBM Corp was used for statistical analysis, and for all analyses, a 2-sided P value of < 0.05 was considered statistically significant. Exclusion criteria were limited to age < 18 years.

RESULTS

Among the 37648180 included individuals in this database who are above the age of 18 years, there were a total of 2320 patients with NAFLD (6.16 per 100000) in the last five years (2015-2020), amongst which 520 patients (22.4%) had hypothyroidism. Baseline characteristics of patients in this database are described in Table 1. Patients with NAFLD were also more likely to have obesity, T2DM, DLP, HTN, and metabolic syndrome (Table 2). While males and females were equally affected, patients in the age group 18-65 years as well as Caucasians seem to be at a higher risk. There was an increased risk of NAFLD among patients with hypothyroidism (OR = 1.587). Furthermore, thyroid hormone replacement was not associated with a decreased risk for developing NAFLD (OR = 1.106, C = 0.952-1.285, P = 0.303).

CONCLUSION

Hypothyroidism seems to be an independent risk factor for the development of NAFLD. Thyroid hormone replacement did not provide a statistically significant risk reduction. Further studies are needed to evaluate the effect of thyroid hormone replacement and assess if being euthyroid while on thyroid replacement therapy affects development and/or progression of NAFLD.

Keywords: Hypothyroidism; Non-alcoholic fatty liver disease; Thyroid hormone replacement therapy; Independent risk factor

Core Tip: One of the largest population-based case-control studies screening more than 37 million patients to study the inconsistent relationship between hypothyroidism and non-alcoholic fatty liver disease (NAFLD), and -to the best of our knowledge- the first paper investigating the theoretical role of thyroid hormone replacement in preventing NAFLD among hypothyroidism patients.