TSH Levels as an Independent Risk Factor for NAFLD and Liver Fibrosis in the General Population

Escudé, Alba Martínez; Pera, Guillem; Costa-Garrido, Anna; Rodríguez, Lluis; Arteaga, Ingrid; Expósito-Martínez, Carmen; Torán-Monserrat, Pere; Caballería, Llorenç

doi:10.3390/jcm10132907

Cited by 18 publications

(13 citation statements)

References 55 publications

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“…To provide stronger evidence of the causality relationship, Bano et al [ 19 ] conducted a prospective cohort study of 9419 patients followed over ten years and observed the effects of hypothyroidism in NAFLD patients, and found a 1.24-fold higher NAFLD risk (95%CI: 1.01-1.53) in patients with hypothyroidism. Another recent descriptive cross-sectional study by Martínez-Escudé et al [ 20 ] reported a significantly higher prevalence of NAFLD and liver fibrosis in subjects with TSH ≥ 2.5 (μIU/mL). Also, in a comparative study of 1773 euthyroid participants, both TSH and levels Free T3 Level were found to be positively associated with the risk of NAFLD when diagnosed by ultrasound and fatty liver index, respectively[ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Prevalence of hypothyroidism and effect of thyroid hormone replacement therapy in patients with non-alcoholic fatty liver disease: A population-based study

Almomani¹,

Hitawala²,

Kumar³

et al. 2022

WJH

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BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is currently considered as the most common cause of chronic liver disease worldwide. Risk factors for NAFLD have been well-described, including obesity, type 2 diabetes mellites (T2DM), dyslipidemia (DLP) and metabolic syndrome. Hypothyroidism has been identified as an independent risk factor for the development of NAFLD, although the literature is inconsistent AIM To evaluate the prevalence of hypothyroidism in patients with NAFLD, assess if it is an independent risk factor and explore the effect of thyroxine replacement therapy. METHODS Our cohort’s data was obtained using a validated, large, multicenter database (Explorys Inc, Cleveland, OH, United States) aggregated from pooled outpatient and inpatient records of 26 different healthcare systems, consisting of a total of 360 hospitals in the United States, and utilizing Systematized Nomenclature of Medicine-Clinical Terms for coding. We evaluated a cohort of patients with hypothyroidism and NAFLD. Multivariate analysis was performed to adjust for confounding risk factors including hypertension (HTN), T2DM, DLP, obesity and metabolic syndrome. SPSS version 25, IBM Corp was used for statistical analysis, and for all analyses, a 2-sided P value of < 0.05 was considered statistically significant. Exclusion criteria were limited to age < 18 years. RESULTS Among the 37648180 included individuals in this database who are above the age of 18 years, there were a total of 2320 patients with NAFLD (6.16 per 100000) in the last five years (2015-2020), amongst which 520 patients (22.4%) had hypothyroidism. Baseline characteristics of patients in this database are described in Table 1 . Patients with NAFLD were also more likely to have obesity, T2DM, DLP, HTN, and metabolic syndrome (Table 2 ). While males and females were equally affected, patients in the age group 18-65 years as well as Caucasians seem to be at a higher risk. There was an increased risk of NAFLD among patients with hypothyroidism (OR = 1.587). Furthermore, thyroid hormone replacement was not associated with a decreased risk for developing NAFLD (OR = 1.106, C = 0.952-1.285, P = 0.303). CONCLUSION Hypothyroidism seems to be an independent risk factor for the development of NAFLD. Thyroid hormone replacement did not provide a statistically significant risk reduction. Further studies are needed to evaluate the effect of thyroid hormone replacement and assess if being euthyroid while on thyroid replacement therapy affects development and/or progression of NAFLD.

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Section: Discussionmentioning

confidence: 99%

Prevalence of hypothyroidism and effect of thyroid hormone replacement therapy in patients with non-alcoholic fatty liver disease: A population-based study

Almomani¹,

Hitawala²,

Kumar³

et al. 2022

WJH

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“…The fact that whether the TH/TR axis can be a risk factor in MAFLD is not clear. Martínez-Escudé A et al (2021) reported that TSH, regarded as a risk factor of MAFLD, is involved in obesity, atherogenic dyslipidemia, metabolic syndrome (MetS), hypertransaminasemia, and altered cholesterol and triglycerides levels. Then, a recent research hint that TSH is a MAFLD risk factor but excludes the FT3 and FT4 levels ( Tan et al, 2021 ).…”

Section: Interplay Between Th/tr Axis and Liver Diseasesmentioning

confidence: 99%

“…Advanced fibrosis is associated with decreased serum FT3 levels ( Du et al, 2021 ). As an independent risk factor, an elevated TSH level is significantly correlated with the risk of fibrosis ( Martínez-Escudé et al, 2021 ). In a recent study, compared with 12.19% in chronic hepatitis C (CHC) patients without thyroid disease (TD), severe fibrosis is found at 92.85% among CHC patients with TD ( Biciusca et al, 2020 ).…”

Section: Interplay Between Th/tr Axis and Liver Diseasesmentioning

confidence: 99%

Targeting Thyroid Hormone/Thyroid Hormone Receptor Axis: An Attractive Therapy Strategy in Liver Diseases

et al. 2022

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Thyroid hormone/thyroid hormone receptor (TH/TR) axis is characterized by TH with the assistance of plasma membrane transporters to combine with TR and mediate biological activities. Growing evidence suggests that TH/TR participates in plenty of hepatic metabolism. Thus, this review focuses on the role of the TH/TR axis in the liver diseases. To be specific, the TH/TR axis may improve metabolic-associated fatty liver disease, hepatitis, liver fibrosis, and liver injury while exacerbating the progression of acute liver failure and alcoholic liver disease. Also, the TH/TR axis has paradoxical roles in hepatocellular carcinoma. The TH/TR axis may be a prospecting target to cure hepatic diseases.

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“…Four studies reported the association between overt hypothyroidism and NASH risk. Four studies investigated the impact of subclinical hypothyroidism, defined as an increased level of serum thyroid stimulating hormone (TSH) with normal FT4, and two studies, by Kim et al [9] and Martínez-Escudé et al [10], used a TSH cut-off of ≥ 2.5, also known as low-normal thyroid function. Low-normal thyroid function was said to be more robust than subclinical hypothyroidism in detecting cardio-metabolic consequences [11,12].…”

Section: Study Characteristicsmentioning

confidence: 99%

“…A novel cut-off of TSH ≥ 2.5, also known as low-normal thyroid function, has been rigorously studied previously, as it better reflects various health problems compared to the traditional cut-off, such as insulin resistance, prediabetes, dyslipidemia, atherosclerotic disease, chronic kidney disease, worse outcome in heart failure patients, and other common cardiometabolic disorders in several population studies [12,[35][36][37]. However, to date, only three studies have investigated the association between low-normal thyroid function and NAFLD, as well as liver fibrosis risk [9,10,38].…”

Section: Bmi -Body Mass Index Bp -Blood Pressure Fib-4 -Fibrosis-4 In...mentioning

confidence: 99%

Association between hypothyroidism and liver fibrosis risk: a systematic review and meta-analysis

Rahadini¹,

Rahadina²

2022

ceh

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Aim of the study: Non-alcoholic fatty liver disease (NAFLD), which encompasses a wide variety of liver pathology, is now the most common chronic liver disease worldwide. The presence of hypothyroidism has been linked to the development of NAFLD. However, its correlation with liver fibrosis, an important clinical entity in NAFLD, is less clear. We aimed to summarize the association between hypothyroidism and liver fibrosis risk. Material and methods:We conducted a search of PubMed and ProQuest from inception to June 30, 2021, for studies assessing the association between hypothyroidism and liver fibrosis risk. The quality of included studies was evaluated using the Newcastle-Ottawa Scale (NOS). We analyzed the pooled odds ratios (ORs) with 95% confidence intervals (CIs) using a fixed and random-effects model. Heterogeneity was assessed using I 2 . Results: Eight studies with a total of 14,588 patients were included. The quality of studies ranged from 6 to 8 stars. Thyroid stimulating hormone (TSH) ≥ 2.5 was significantly associated with increased risk of significant liver fibrosis (OR = 1.61, 95% CI = 1.21-2.15). Subclinical hypothyroidism was also correlated with an increased risk of advanced fibrosis (OR = 2.77, 95% CI = 1.65-4.65). A significant association was found between overt hypothyroidism and non-alcoholic steatohepatitis (NASH) risk (OR = 2.38, 95% CI = 1.61-3.53). However, no significant association was found between subclinical hypothyroidism and significant liver fibrosis. Conclusions: Hypothyroidism is associated with an increased risk of fibrosis in NAFLD patients.

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TSH Levels as an Independent Risk Factor for NAFLD and Liver Fibrosis in the General Population

Cited by 18 publications

References 55 publications

Prevalence of hypothyroidism and effect of thyroid hormone replacement therapy in patients with non-alcoholic fatty liver disease: A population-based study

Prevalence of hypothyroidism and effect of thyroid hormone replacement therapy in patients with non-alcoholic fatty liver disease: A population-based study

Targeting Thyroid Hormone/Thyroid Hormone Receptor Axis: An Attractive Therapy Strategy in Liver Diseases

Association between hypothyroidism and liver fibrosis risk: a systematic review and meta-analysis

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