Evidence on the link between hypothyroidism and non-alcoholic fatty liver disease: an updated systematic review.

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• Thyroid health and liver health are closely linked, with hypothyroidism commonly observed alongside NAFLD.

• People with thyroid dysfunction may have a higher likelihood of developing liver fat accumulation.

• Managing metabolic risk factors, including body weight and insulin resistance, may help protect both thyroid and liver health.

Introduction

This study aimed to assess the association between non-alcoholic fatty liver disease (NAFLD) and hypothyroidism in non-diabetic adults.

Methods

This was a systematic review of twenty-nine observational studies amongst which nineteen were cross-sectional, five case-control and five cohort studies. Sample sizes ranged from 90 to 114,866 adult participants. It followed the PRISMA guidelines.

Results 

Results showed that:

• cross-sectional studies demonstrated significant associations between hypothyroidism and NAFLD, including elevated odds of NAFLD in individuals with subclinical or overt hypothyroidism versus euthyroid controls e.g., in Chung et al. (2012) - OR = 1.38, 95% CI: 1.17-1.62, p = 0.001 and Shatla et al. (2021) - p < 0.001, and lower serum free T4 levels linked with higher NAFLD risk e.g., in Xu et al. (2011) - OR = 0.847, 95% CI: 0.743-0.966, p = 0.013.

• case-control studies consistently found higher prevalence of hypothyroidism among NAFLD cases versus controls, with increased risk associated with higher thyroid stimulating hormone (TSH) levels e.g., in Fan et al. (2022) - OR = 1.29, 95% CI: 1.10-1.52; Labenz et al. (2021) - OR = 1.17, 95% CI: 1.10-1.24, and autoimmune thyroiditis OR = 1.53, 95% CI: 1.35-1.73; p < 0.001.

• prospective cohort studies reported an increased risk of NAFLD with hypothyroidism. Bano et al. (2016) showed hypothyroidism associated with a 1.24-fold higher risk (95% CI: 1.01-1.53) compared with euthyroid status.
  

• additional cohort evidence indicated that within euthyroid ranges, high-normal free T3 was positively associated with NAFLD incidence (HR = 1.30, 95% CI: 1.12-1.51), and low-normal TSH inversely associated (HR = 0.82, 95% CI: 0.71-0.95).
  

• the cohort study of Lee et al. (2018) did not find significant differences in NAFLD incidence by thyroid status after multivariable adjustment (subclinical hypothyroidism HR = 0.965, 95% CI: 0.814-1.143; overt hypothyroidism HR = 1.25, 95% CI: 0.830-1.899).

Conclusion

Current observational evidence suggests an association between hypothyroidism and an increased risk of NAFLD, highlighting the importance of mutual screening and integrated management strategies. However, given the reliance on observational studies with variable methodological quality, these findings should be interpreted with caution.

• Regular assessment of thyroid function may be considered in patients with NAFLD to support early identification and management of overt or subclinical hypothyroidism.

• Measurement of serum TSH and free thyroxine levels may be particularly relevant in NAFLD patients with obesity, insulin resistance, or other metabolic abnormalities.

• Early identification of coexisting thyroid dysfunction and NAFLD may facilitate timely lifestyle and therapeutic interventions, potentially improving metabolic and hepatic outcomes.

• Integrating thyroid and liver assessments into routine metabolic evaluations may support more comprehensive, multidisciplinary patient management.

• Future studies should aim to standardise NAFLD diagnostic methods to reduce variability in sensitivity and specificity and improve comparability of findings.

• Prospective cohort studies and well-designed randomised controlled trials are needed to clarify temporal and causal relationships between hypothyroidism and NAFLD, overcoming inherent limitations of cross-sectional and observational designs.

• Research exploring the influence of genetic polymorphisms, molecular pathways, and gene-environment interactions could elucidate biological mechanisms linking hypothyroidism and NAFLD

• Larger, multi-ethnic population studies are needed to determine whether associations vary by demographic, metabolic, or clinical characteristics.