Elsevier

Journal of Hepatology

Volume 57, Issue 1, July 2012, Pages 150-156
Journal of Hepatology

Research Article
Non-alcoholic fatty liver disease across the spectrum of hypothyroidism

https://doi.org/10.1016/j.jhep.2012.02.027Get rights and content

Background & Aims

The aim of this study was to characterize the relationship between the broad spectrum of hypothyroidism and NAFLD.

Methods

A cross-sectional study with 4648 health check-up subjects (2324 cases with hypothyroidism vs. age- and sex-matched controls) was conducted. The subjects were categorized as having either subclinical [thyroid-stimulating hormone (TSH) ⩾4.1 mIU/L and normal free thyroixine (T4) level (0.7–1.8 ng/dl)] or overt hypothyroidism [free T4 <0.7 ng/dl]. NAFLD was diagnosed on the basis of typical ultrasonographic findings, and alcohol consumption of less than 20 g/day in the absence of other causes of liver disease.

Results

The mean age of the subjects was 48.6 ± 11.8 years and 62.4% were female. NAFLD was significantly associated with hypothyroidism (30.2% patients vs. 19.5% control, p <0.001). The prevalence of NAFLD and abnormal liver enzyme levels (ALT >33/25 IU/L) increased steadily with increasing grades of hypothyroidism (for NAFLD, subclinical: 29.9% and overt: 36.3%; for abnormal ALT, 20.1% and 25.9%, p <0.001, respectively). Multivariate regression analysis showed that NAFLD was statistically significantly associated with hypothyroidism (odds ratio (OR) 1.38, 95% confidence interval (CI), 1.17–1.62) and the grade of hypothyroidism in a dose-dependent manner (OR 1.36, 95% CI, 1.16–1.61 in subclinical hypothyroidism and OR 1.71, 95% CI, 1.10–2.66 in overt hypothyroidism).

Conclusions

Subclinical hypothyroidism, even in the range of upper normal TSH levels, was found to be related to NAFLD in a dose-dependent manner. Hypothyroidism is closely associated with NAFLD independently of known metabolic risk factors, confirming a relevant clinical relationship between these two diseases.

Introduction

Non-alcoholic fatty liver disease (NAFLD) has been recognized as the most common liver disease, and it includes a spectrum of hepatic dysfunctions ranging from simple steatosis to non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma [1], [2]. Because the mechanism underlying the development of NAFLD has been linked to insulin resistance and metabolic syndrome, NAFLD is considered to be the hepatic manifestation of metabolic syndrome [3], [4], [5], and the associations with many predictors of cardiovascular disease have been reported [6], [7], [8], [9].

Thyroid dysfunction is a common condition that affects lifelong health [10]. Subclinical hypothyroidism, which refers to an elevated thyroid-stimulating hormone (TSH) level and a normal free thyroxine (T4) level, has been associated with metabolic syndrome, cardiovascular diseases and mortality [11], [12], [13], [14]. Because thyroid hormones play a fundamental role in lipid metabolism [15], hypothyroidism may cause hypercholesterolemia and play an essential role in the pathogenesis of NAFLD [16], [17]. Previous studies have reported that thyroid dysfunction is associated with liver diseases, including chronic hepatitis C [18], hepatocellular carcinoma [19], primary biliary cirrhosis, and primary sclerosing cholangitis [17]. Furthermore, a recent study showed that the prevalence of NAFLD is negatively correlated with free T4 levels, and decreased free T4 levels contribute to the risk of NAFLD [20]. Although a relationship between thyroid function and NAFLD has been suggested in an elderly euthyroidic population [20], associations between NAFLD and the full spectrum of hypothyroidism in the general population have not been well studied.

Therefore, we conducted a cross-sectional study to evaluate the prevalence and association of NAFLD according to the spectrum of hypothyroidism in a large healthy population.

Section snippets

Study population

A total of 71,780 subjects visited Seoul National University Hospital, Healthcare System Gangnam Center, Seoul, South Korea for a routine health check-up between October 2006 and October 2009. Among the total screenees, subjects with thyroid dysfunction, including both subclinical and overt hypothyroidism, were included as cases. Eighty-four subjects who take medications, such as thyroid hormone or antithyroid drugs, were excluded. Three hundred and twenty-one subjects with excessive alcohol

Baseline characteristics

A total of 2324 pairs of subjects with thyroid dysfunction and age- and sex-matched controls (1450 pairs of females and 874 pairs of males) were finally enrolled. The mean age was 48.6 ± 11.8 years and 62.4% were female. The anthropometric, clinical, and laboratory characteristics of the subjects are shown in Table 1. The BMI, waist circumference, serum ALT, AST, glucose, triglyceride, systolic blood pressure, and diastolic blood pressure were all significantly different between the hypothyroidism

Discussion

The principal finding of our study was a strong association of NAFLD with hypothyroidism. The prevalence of both NAFLD and elevated liver enzyme levels was significantly greater in subjects with hypothyroidism than in subjects with normal thyroid function. Additionally, the spectrum of hypothyroidism was found to be related to NAFLD in a dose-dependent manner. These findings suggest that hypothyroidism is closely associated with NAFLD independently of known metabolic risk factors, confirming

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

Financial support

This work was funded by Grant 04-2010-104 from the Seoul National University Hospital Research Fund.

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