Subclinical hypothyroidism and low-normal thyroid function are associated with nonalcoholic steatohepatitis and fibrosis
Abstract
Background & aims Variations in level of thyroid-stimulating hormone (TSH) within the reference range of thyroid hormone could have negative health effects. We evaluated the effect of plasma TSH levels within the euthyroid range on the severity of histological damage associated with nonalcoholic fatty liver disease (NAFLD).Methods We performed a cross-sectional study of 425 subjects with biopsy-proven NAFLD (mean age, 53 years; 52% male) who participated in the Boramae NAFLD study from January 2013 to January 2017. Each subject underwent an anthropometric assessment and laboratory and clinical evaluations. Of the subjects, 282 were assigned to a strict-normal thyroid function group (plasma level of TSH, 0.4 to 2.5 mIU/L). Patients with low thyroid function were assigned to groups of subclinical hypothyroidism (plasma level of TSH above 4.5 mIU/L with a normal thyroid hormone level; n = 59) or low-normal thyroid function (higher plasma TSH level [2.5 to 4.5 mIU/L] with a normal thyroid hormone level; n = 84). Multivariate logistic regression analysis was used to identify factors independently associated with nonalcoholic steatohepatitis (NASH) and advanced fibrosis.Results NASH and advanced fibrosis were found in higher percentages of subjects with low thyroid function vs strict-normal thyroid function (52.4% vs 37.2% for NASH and 21.0% vs 10.6% for advanced fibrosis; P < .01). Among subjects with low thyroid function, a higher proportion of patients with subclinical hypothyroidism had NASH and associated advanced fibrosis vs patients with low-normal thyroid function (57.6% vs 48.8% for NASH and 25.4% vs 17.9% for advanced fibrosis; P < .01). Subjects with low thyroid function had more extensive hepatic steatosis with greater severity of balloon degeneration and fibrosis. In multivariate analyses, low thyroid function was significantly associated with NASH (odds ratio, 1.61; 95% CI, 1.04-2.50; P = .035) and advanced fibrosis (odds ratio, 2.23; 95% CI, 1.18-4.23; P = .014). Risks of NASH and advanced fibrosis increased significantly with plasma concentration of TSH (Ptrend <.05 for each).Conclusions Subclinical hypothyroidism and low-normal thyroid function are independent predictors of NASH and advanced fibrosis, confirming the relationship between these diseases. ClinicalTrials.gov, Number: NCT02206841.
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The incidence of clinical and subclinical hypothyroidism appears higher in individuals with MASLD or MASH relative to age-matched controls, and low thyroid function is associated with more severe outcomes.
“The incidence of clinical and subclinical hypothyroidism appears to be higher in individuals with MASLD or MASH relative to age-matched controls, and low thyroid function is associated with more severe outcomes.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [345]
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- Authors
- Kim, D., Kim, W., Joo, S. K., Bae, J. M., Kim, J. H., & Ahmed, A.
- Affiliations
- Stanford Medicine (US)
- Seoul National University (KR)
- Corresponding author
- Kim, Donghee
- Kim, Won
- Venue
- Clinical Gastroenterology and Hepatology
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 16
- Issue
- 1
- Pages
- 123-131.e1
- ISSN
- 1542-3565 (ISSN-L)
- OpenAlex
- W2745721913
- Cited by
- 191
- References
- 36
- Citations by year
- 2026: 13 · 2025: 23 · 2024: 26 · 2023: 16 · 2022: 37 · 2021: 24 · 2020: 21 · 2019: 20 · 2018: 11
- FWCI
- 11.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Gastroenterology and Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- subclinical hypothyroidism, thyroid-stimulating hormone, nonalcoholic steatohepatitis, liver fibrosis, non-alcoholic fatty liver disease, hepatic steatosis, Korean adults, sex differences, age differences, body mass index, alcohol consumption
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Female, Humans, Hypothyroidism, Liver Cirrhosis, Male, Middle Aged, Thyrotropin, Young Adult, Asymptomatic Diseases, Non-alcoholic Fatty Liver Disease
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