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Association Between Primary Hypothyroidism and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.
Thyroid. 2018 10; 28(10):1270-1284.T

Abstract

BACKGROUND

It is currently uncertain whether primary hypothyroidism is associated with nonalcoholic fatty liver disease (NAFLD). We performed a meta-analysis of relevant studies to quantify the magnitude of association between primary hypothyroidism and risk of NAFLD.

METHODS

We searched PubMed, Web of Science and Scopus databases from January 2000 to March 2018 using predefined keywords to identify observational cross-sectional, case-control, and longitudinal studies in which NAFLD was diagnosed by imaging or biopsy. Data from selected studies were extracted and meta-analysis was performed using random-effects modeling.

RESULTS

A total of 12 cross-sectional and 3 longitudinal studies enrolling 44,140 individuals were included in the final analysis. Hypothyroidism (defined either by self-reported history of hypothyroidism with use of levothyroxine replacement therapy or by presence of abnormal thyroid function tests) was associated with an increased risk of prevalent NAFLD (n = 12 studies; random-effects odds ratio 1.42 [95% confidence interval (CI) 1.15-1.77]; I2 = 51.2%), independently of age, sex, body mass index and other common metabolic risk factors. The magnitude of risk paralleled the underlying severity of NAFLD histology (n = 3 studies; random-effects odds ratio 2.73 [CI 1.90-3.93]; I2 = 0%), and tended to increase across the different definitions used for diagnosing hypothyroidism. Meta-analysis of data from the three longitudinal studies showed that subclinical hypothyroidism was not independently associated with risk of incident ultrasound-defined NAFLD over a median of 5 years (random-effects hazard ratio 1.29 [CI 0.89-1.86]; I2 = 83.9%). Sensitivity analyses did not alter these findings. Funnel plot did not reveal significant publication bias.

CONCLUSIONS

This large and updated meta-analysis shows that the presence of variably defined hypothyroidism is significantly associated with the presence and severity of NAFLD. However, the observational design of the eligible studies does not allow for proving causality.

Authors+Show Affiliations

1 Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona , Verona, Italy .2 Department of Internal Medicine and Metabolic Diseases, Nuovo Ospedale Sant'Agostino Estense di Baggiovara, Modena, Italy .2 Department of Internal Medicine and Metabolic Diseases, Nuovo Ospedale Sant'Agostino Estense di Baggiovara, Modena, Italy .1 Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona , Verona, Italy .1 Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona , Verona, Italy .3 Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center , Harvard Medical School, Boston, Massachusetts.1 Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona , Verona, Italy .

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

Language

eng

PubMed ID

30084737

Citation

Mantovani, Alessandro, et al. "Association Between Primary Hypothyroidism and Nonalcoholic Fatty Liver Disease: a Systematic Review and Meta-Analysis." Thyroid : Official Journal of the American Thyroid Association, vol. 28, no. 10, 2018, pp. 1270-1284.
Mantovani A, Nascimbeni F, Lonardo A, et al. Association Between Primary Hypothyroidism and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Thyroid. 2018;28(10):1270-1284.
Mantovani, A., Nascimbeni, F., Lonardo, A., Zoppini, G., Bonora, E., Mantzoros, C. S., & Targher, G. (2018). Association Between Primary Hypothyroidism and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Thyroid : Official Journal of the American Thyroid Association, 28(10), 1270-1284. https://doi.org/10.1089/thy.2018.0257
Mantovani A, et al. Association Between Primary Hypothyroidism and Nonalcoholic Fatty Liver Disease: a Systematic Review and Meta-Analysis. Thyroid. 2018;28(10):1270-1284. PubMed PMID: 30084737.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association Between Primary Hypothyroidism and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. AU - Mantovani,Alessandro, AU - Nascimbeni,Fabio, AU - Lonardo,Amedeo, AU - Zoppini,Giacomo, AU - Bonora,Enzo, AU - Mantzoros,Christos S, AU - Targher,Giovanni, Y1 - 2018/08/30/ PY - 2018/8/8/pubmed PY - 2019/6/25/medline PY - 2018/8/8/entrez KW - NAFLD KW - hypothyroidism KW - meta-analysis KW - thyroid dysfunction liver fat SP - 1270 EP - 1284 JF - Thyroid : official journal of the American Thyroid Association JO - Thyroid VL - 28 IS - 10 N2 - BACKGROUND: It is currently uncertain whether primary hypothyroidism is associated with nonalcoholic fatty liver disease (NAFLD). We performed a meta-analysis of relevant studies to quantify the magnitude of association between primary hypothyroidism and risk of NAFLD. METHODS: We searched PubMed, Web of Science and Scopus databases from January 2000 to March 2018 using predefined keywords to identify observational cross-sectional, case-control, and longitudinal studies in which NAFLD was diagnosed by imaging or biopsy. Data from selected studies were extracted and meta-analysis was performed using random-effects modeling. RESULTS: A total of 12 cross-sectional and 3 longitudinal studies enrolling 44,140 individuals were included in the final analysis. Hypothyroidism (defined either by self-reported history of hypothyroidism with use of levothyroxine replacement therapy or by presence of abnormal thyroid function tests) was associated with an increased risk of prevalent NAFLD (n = 12 studies; random-effects odds ratio 1.42 [95% confidence interval (CI) 1.15-1.77]; I2 = 51.2%), independently of age, sex, body mass index and other common metabolic risk factors. The magnitude of risk paralleled the underlying severity of NAFLD histology (n = 3 studies; random-effects odds ratio 2.73 [CI 1.90-3.93]; I2 = 0%), and tended to increase across the different definitions used for diagnosing hypothyroidism. Meta-analysis of data from the three longitudinal studies showed that subclinical hypothyroidism was not independently associated with risk of incident ultrasound-defined NAFLD over a median of 5 years (random-effects hazard ratio 1.29 [CI 0.89-1.86]; I2 = 83.9%). Sensitivity analyses did not alter these findings. Funnel plot did not reveal significant publication bias. CONCLUSIONS: This large and updated meta-analysis shows that the presence of variably defined hypothyroidism is significantly associated with the presence and severity of NAFLD. However, the observational design of the eligible studies does not allow for proving causality. SN - 1557-9077 UR - https://www.unboundmedicine.com/medline/citation/30084737/Association_Between_Primary_Hypothyroidism_and_Nonalcoholic_Fatty_Liver_Disease:_A_Systematic_Review_and_Meta_Analysis_ L2 - https://www.liebertpub.com/doi/10.1089/thy.2018.0257?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -