Relationship between Hypothyroidism and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis

Abstract

BackgroundPrevious studies propose that hypothyroidism might play a crucial role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), but findings from published studies on the relationship between hypothyroidism and NAFLD are still controversial. Our study aimed to make a comprehensive evaluation of the relationship between hypothyroidism and NAFLD through a meta-analysis.MethodsPubMed, China Dissertation Database, and EMBASE databases were searched to find observational studies assessing the relationship between hypothyroidism and NAFLD. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to evaluate the strength of the relationship between hypothyroidism and NAFLD through meta-analysis.ResultsThirteen articles were ultimately included in our meta-analysis. Meta-analysis of the 13 studies found a high correlation between hypothyroidism and NAFLD (OR = 1.52, 95% CI 1.24–1.87, P < 0.001). Meta-analysis of 9 studies providing adjusted ORs found that hypothyroidism was independently correlated with NAFLD (OR = 1.72, 95% CI 1.32–2.23, P < 0.001). Subgroup analysis found that both overt hypothyroidism and subclinical hypothyroidism were significantly correlated with NAFLD, and the pooled ORs were 1.70 (95% CI 1.23–2.36, P = 0.002) and 1.40 (95% CI 1.10–1.77, P = 0.006), respectively. Besides, meta-analysis of studies providing adjusted ORs also found that both overt hypothyroidism and subclinical hypothyroidism were independently correlated with NAFLD, and the pooled ORs were 1.81 (95% CI 1.30–2.52, P < 0.001) and 1.63 (95% CI 1.19–2.24, P = 0.002), respectively.ConclusionThe meta-analysis provides strong epidemiological evidence for the relationship between hypothyroidism and NAFLD. Both individuals with subclinical and overt hypothyroidism are at higher risk for NAFLD than euthyroid subjects.

Nonalcoholic Fatty Liver Disease: A Challenge from Mechanisms to Therapy

“…A recent meta-analysis provides strong epidemiological evidence for the relationship between hypothyroidism and NAFLD. Both patients with subclinical and overt hypothyroidism are at major risk for NAFLD than euthyroid subjects [103].…”

Association Between Primary Hypothyroidism and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

“…Our meta-analysis exploring the association between variably defined primary hypothyroidism and the risk of NAFLD is the largest and most comprehensive assessment to date. Two previous smaller meta-analyses have yielded controversial findings (25,26]. One meta-analytic study of nine studies (involving a total of *32,000 subjects) showed that patients with NAFLD had no significant differences in serum thyroid hormone levels compared with control individuals and that there was no significant association between variably defined primary hypothyroidism and NAFLD (random-effects OR 1.21 [CI 0.91-1.61]; I 2 = 72%) (25).…”

“…In addition, they did not include studies performed in adolescents (23,24), and crosssectional or longitudinal studies published in adults from 2016 to 2018 (20)(21)(22). Conversely, in the other published meta-analysis of 13 cross-sectional and longitudinal studies (involving a total of *41,000 subjects), He et al reported a significant association between variably defined primary hypothyroidism and the risk of NAFLD (random-effects OR 1.52 [CI 1.24-1.87]; I 2 = 75.1%) (26). Compared with our meta-analysis, these authors have included eleven studies identical to those included in our meta-analysis (10)(11)(12)(13)(15)(16)(17)19,20,23,24), but also an unpublished M.D.…”

“…For the aforementioned reasons, we believe that the findings of these two previous meta-analyses should be interpreted cautiously, especially because they have important methodological limitations (combining, for example, the results of both cross-sectional and longitudinal studies within the same pooled primary analysis; including a number of studies of very low quality according to the NOS scale; not performing extensive sensitivity analyses to explore possible sources of heterogeneity) and did not consider much of the currently available evidence (mainly the studies published in 2017 and 2018, which we have included in our metaanalysis). As a result of these methodological limitations, it should also be noted that in both meta-analyses there was a very high degree of heterogeneity (I 2 ‡ 72%) for the pooled primary analysis, and the visual inspection of the funnel plots showed the presence of significant publication bias (25,26).…”

“…This finding raised concern as to whether subclinical hypothyroidism could be associated with an increased risk of NAFLD. Although two previous small meta-analyses have further explored this question, they had important methodological limitations (e.g., pooling of cross-sectional and longitudinal studies; very high heterogeneity and significant publication bias of results) and did not consider much of the currently available evidence (i.e., studies published in 2017 and 2018), thus providing controversial and inconclusive findings (25,26). On this background of evidence, it still remains uncertain whether subclinical hypothyroidism is a risk factor for NAFLD.…”