Background: Whether hypothyroidism is related to nonalcoholic fatty liver disease (NAFLD) is unclear. Thyroid dysfunction is closely related with components of metabolic syndrome. Given the hepatic manifestation of metabolic syndrome, several studies have investigated the association between NAFLD and thyroid dysfunction and have demonstrated inconsistent results. Thus, we conducted a systematic review and meta-analysis to better characterize the association between NAFLD and thyroid dysfunction. Methods: MEDLINE and Embase were searched through July 2016. The primary outcome was the association between NAFLD and subclinical, overt, and overall hypothyroidism. The secondary outcome was the difference in thyroid hormone levels (free triiodothyronine [FT3], free thyroxine [FT4], or thyroid-stimulating hormone [TSH]) between NAFLD patients and non-NAFLD controls. Pooled odds ratios (OR) and 95% CI were calculated using a random-effects model. All continuous data are summarized as the mean difference along with 95% CI. Results: Data were extracted from 14 studies involving 7,191 NAFLD patients and 30,003 controls. NAFLD was not associated with subclinical, overt, or overall hypothyroidism compared with non-NAFLD controls. Patients who had NAFLD did not show a significant difference in FT3, FT4, or TSH compared with non-NAFLD controls. Conclusions: Our meta-analysis demonstrates no significant association between NAFLD and subclinical, overt, or overall hypothyroidism, and we also found no significant difference in thyroid hormone levels between participants with and without NAFLD.

Keywords:
Hypothyroidism, Meta-analysis, Nonalcoholic fatty liver disease, Thyroid function
1.
Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M: Global epidemiology of nonalcoholic fatty liver disease - meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016;64:73-84.
2.
Angulo P: Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221-1231.
3.
Rinella ME: Nonalcoholic fatty liver disease: a systematic review. JAMA 2015;313:2263-2273.
4.
Zezos P, Renner EL: Liver transplantation and non-alcoholic fatty liver disease. World J Gastroenterol 2014;20:15532-15538.
5.
Jaruvongvanich V, Sanguankeo A, Upala S: Significant association between gallstone disease and nonalcoholic fatty liver disease: a systematic review and meta-analysis. Dig Dis Sci 2016;61:2389-2396.
6.
Lopez-Suarez A, Guerrero JM, Elvira-Gonzalez J, Beltran-Robles M, Canas-Hormigo F, Bascunana-Quirell A: Nonalcoholic fatty liver disease is associated with blood pressure in hypertensive and nonhypertensive individuals from the general population with normal levels of alanine aminotransferase. Eur J Gastroenterol Hepatol 2011;23:1011-1017.
7.
Pucci E, Chiovato L, Pinchera A: Thyroid and lipid metabolism. Int J Obes Relat Metab Disord 2000;24(suppl 2):S109-S112.
8.
Sinha RA, Singh BK, Yen PM: Thyroid hormone regulation of hepatic lipid and carbohydrate metabolism. Trends Endocrinol Metab 2014;25:538-545.
9.
Erdogan M, Canataroglu A, Ganidagli S, Kulaksizoglu M: Metabolic syndrome prevalence in subclinic and overt hypothyroid patients and the relation among metabolic syndrome parameters. J Endocrinol Invest 2011;34:488-492.
10.
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB: Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-Analysis of Observational Studies in Epidemiology (MOOSE) Group. JAMA 2000;283:2008-2012.
11.
Stang A: Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010;25:603-605.
12.
Higgins JP, Thompson SG, Deeks JJ, Altman DG: Measuring inconsistency in meta-analyses. BMJ 2003;327:557-560.
13.
Sterne JA, Egger M: Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. J Clin Epidemiol 2001;54:1046-1055.
14.
Chung GE, Kim D, Kim W, Yim JY, Park MJ, Kim YJ, Yoon JH, Lee HS: Non-alcoholic fatty liver disease across the spectrum of hypothyroidism. J Hepatol 2012;57:150-156.
15.
Ding WJ, Wang MM, Wang GS, Shen F, Qin JJ, Fan JG: Thyroid function is associated with non-alcoholic fatty liver disease in chronic hepatitis B-infected subjects. J Gastroenterol Hepatol 2015;30:1753-1758.
16.
Eshraghian A, Dabbaghmanesh MH, Eshraghian H, Fattahi MR, Omrani GR: Nonalcoholic fatty liver disease in a cluster of Iranian population: thyroid status and metabolic risk factors. Arch Iran Med 2013;16:584-589.
17.
Gokmen FY, Ahbab S, Ataoglu HE, Turker BC, Cetin F, Turker F, Mamac RY, Yenigun M: FT3/FT4 ratio predicts non-alcoholic fatty liver disease independent of metabolic parameters in patients with euthyroidism and hypothyroidism. Clinics (Sao Paulo) 2016;71:221-225.
18.
Ittermann T, Haring R, Wallaschofski H, Baumeister SE, Nauck M, Dorr M, Lerch MM, Meyer zu Schwabedissen HE, Rosskopf D, Volzke H: Inverse association between serum free thyroxine levels and hepatic steatosis: results from the Study of Health in Pomerania. Thyroid 2012;22:568-574.
19.
Liu G, Zheng X, Guan L, Jiang Z, Lin H, Jiang Q, Zhang N, Zhang Y, Zhang X, Yu C, Guan Q: Free triiodothyronine levels are positively associated with non-alcoholic fatty liver disease in euthyroid middle-aged subjects. Endocr Res 2015;40:188-193.
20.
Ludwig U, Holzner D, Denzer C, Greinert A, Haenle MM, Oeztuerk S, Koenig W, Boehm BO, Mason RA, Kratzer W, Graeter T, EMIL-Study: Subclinical and clinical hypothyroidism and non-alcoholic fatty liver disease: a cross-sectional study of a random population sample aged 18-65 years. BMC Endocr Disord 2015;15:41.
21.
Tao Y, Gu H, Wu J, Sui J: Thyroid function is associated with non-alcoholic fatty liver disease in euthyroid subjects. Endocr Res 2015;40:74-78.
22.
Xu C, Xu L, Yu C, Miao M, Li Y: Association between thyroid function and nonalcoholic fatty liver disease in euthyroid elderly Chinese. Clin Endocrinol 2011;75:240-246.
23.
Liangpunsakul S, Chalasani N: Is hypothyroidism a risk factor for non-alcoholic steatohepatitis? J Clin Gastroenterol 2003;37:340-343.
24.
Moustafa AH, Ali EM, Mohamed TM, Abdou HI: Oxidative stress and thyroid hormones in patients with liver diseases. Eur J Intern Med 2009;20:703-708.
25.
Parikh P, Phadke A, Sawant P: Prevalence of hypothyroidism in nonalcoholic fatty liver disease in patients attending a tertiary hospital in western India. Indian J Gastroenterol 2015;34:169-173.
26.
Zhang J, Sun H, Chen L, Zheng J, Hu X, Wang S, Chen T: Relationship between serum TSH level with obesity and NAFLD in euthyroid subjects. J Huazhong Univ Sci Technolog Med Sci 2012;32:47-52.
27.
Lee KW, Bang KB, Rhee EJ, Kwon HJ, Lee MY, Cho YK: Impact of hypothyroidism on the development of non-alcoholic fatty liver disease: a 4-year retrospective cohort study. Clin Mol Hepatol 2015;21:372-378.
28.
Leonhardt U, Ritzel U, Schäfer G, Becker W, Ramadori G: Serum leptin levels in hypo- and hyperthyroidism. J Endocrinol 1998;157:75-79.
29.
Polyzos SA, Aronis KN, Kountouras J, Raptis DD, Vasiloglou MF, Mantzoros CS: Circulating leptin in non-alcoholic fatty liver disease: a systematic review and meta-analysis. Diabetologia 2016;59:30-43.
30.
Ikejima K, Okumura K, Lang T, Honda H, Abe W, Yamashina S, Enomoto N, Takei Y, Sato N: The role of leptin in progression of non-alcoholic fatty liver disease. Hepatol Res 2005;33:151-154.
31.
Lee Y, Park YJ, Ahn HY, Lim JA, Park KU, Choi SH, Park do J, Oh BC, Jang HC, Yi, KH: Plasma FGF21 levels are increased in patients with hypothyroidism independently of lipid profile. Endocr J 2013;60:977-983.
32.
Rusli F, Deelen J, Andriyani E, Boekschoten MV, Lute C, van den Akker EB, Müller M, Beekman M, Steegenga WT: Fibroblast growth factor 21 reflects liver fat accumulation and dysregulation of signalling pathways in the liver of C57BL/6J mice. Sci Rep 2016;6:30484.
33.
Lee SS, Park SH: Radiologic evaluation of nonalcoholic fatty liver disease. World J Gastroenterol 2014;20:7392-7402.
© 2017 European Thyroid Association Published by S. Karger AG, Basel
2017
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