Original article
Pancreas, biliary tract, and liver
Subclinical Hypothyroidism and Low-Normal Thyroid Function Are Associated With Nonalcoholic Steatohepatitis and Fibrosis

https://doi.org/10.1016/j.cgh.2017.08.014Get rights and content

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.

Section snippets

Subjects and Study Design

In this study, we analyzed data from a previously described cohort.17 Briefly, we enrolled eligible subjects from the Boramae NAFLD cohort (NCT02206841) from January 2013 to January 2017. The eligibility criteria for this cohort were as follows: 1) ≥18 years of age; 2) ultrasonography-diagnosed fatty liver (increased liver/kidney echogenicity and posterior attenuation); and 3) unexplained high alanine aminotransferase (ALT) levels above the reference range within the past 6 months.18 We

Baseline Characteristics in Subjects With Low-Normal Thyroid Function or Subclinical Hypothyroidism Compared With Those With Strict-Normal Thyroid Function

Among the 425 subjects (mean age, 53 years; 52% men) with biopsy-proven NAFLD, 282 subjects were classified in the strict-normal thyroid function group, 84 in the low-normal thyroid function group, and 59 in the subclinical hypothyroidism group. The baseline characteristics of this cohort are shown in Table 1. With regard to age and gender, the groups were similar. The BMI, waist circumference, serum ALT level, aspartate aminotransferase (AST) level, HOMA-IR, and prevalence of current smoking

Discussion

We report a strong association of biopsy-proven NASH or associated advanced fibrosis with increasing plasma TSH levels in a dose-dependent manner even within the normal clinical ranges of T4 as our main finding. The prevalence of NASH and advanced fibrosis was significantly higher in subjects with subclinical hypothyroidism than in those with normal thyroid function. These findings suggest that higher TSH levels even within the normal range are closely associated with NASH and NASH-related

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    Conflicts of interest The authors disclose no conflicts.

    Funding This work was supported by the National Research Foundation of Korea grant funded by the Korea government (MEST) (2016R1D1A1B04934590), and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health & Welfare, Republic of Korea (H I17C0912).

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    Authors share co-first authorship.

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