Thyroid Dysfunction and Non-Alcoholic Fatty Liver Disease
Summary
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of hepatic disorders characterised by excessive lipid accumulation in hepatocytes in the absence of significant alcohol consumption. Its prevalence has risen globally in parallel with obesity and metabolic syndrome. Thyroid dysfunction, especially hypothyroidism and low-normal thyroid states, has emerged as an important modifiable risk factor in NAFLD pathogenesis. Reduced thyroid hormone action impairs lipid mobilisation and mitochondrial energy expenditure in the liver, favouring steatosis. Conversely, altered hepatic thyroid hormone metabolism—driven by changes in deiodinase expression during inflammation and fibrogenesis—can induce intrahepatic hypothyroidism, further aggravating lipid deposition and insulin resistance. Understanding the bidirectional interplay between thyroid status and liver pathology has opened new avenues for therapeutic intervention, including selective thyromimetics and hormone replacement, with potential to ameliorate liver injury, improve lipid profiles and slow progression to steatohepatitis and fibrosis.
Research from Nature Portfolio
A 2023 phase III trial evaluated a liver-directed thyroid hormone receptor-β agonist in adults with presumed non-alcoholic steatohepatitis. Over 52 weeks, patients receiving the active compound at two dose levels exhibited substantial reductions in hepatic fat content, measured by non-invasive imaging, alongside improvements in low-density lipoprotein cholesterol, apolipoprotein B and triglycerides. Liver stiffness measurements also declined relative to placebo, without serious safety concerns. These findings establish proof of concept for selective thyroid receptor modulation in fatty liver disease and support further exploration of thyromimetic agents as targeted treatments for steatohepatitis.
Thyroid Dysfunction and Non-Alcoholic Fatty Liver Disease publication trend
The graph below shows the total number of articles in thyroid dysfunction and non-alcoholic fatty liver disease across all publications each year (not limited to Nature Index journals).
Technical terms
Non-alcoholic fatty liver disease (NAFLD): Accumulation of triglycerides in the liver in individuals who consume little or no alcohol.
Non-alcoholic steatohepatitis (NASH/MASH): A progressive form of NAFLD characterised by hepatocyte inflammation, ballooning and variable fibrosis.
Thyroid hormone receptor-β (THR-β): A nuclear receptor isoform predominantly expressed in liver that mediates the genomic actions of thyroid hormones on lipid and energy metabolism.
Subclinical hypothyroidism: A state of elevated thyroid-stimulating hormone with circulating free thyroxine within the reference range, often asymptomatic.
Deiodinases: Enzymes (D1, D2, D3) that activate or inactivate thyroid hormones by removing iodine atoms, regulating local tissue hormone availability.
References
- Resmetirom for nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled phase 3 trial. Nature Medicine (2023).
- Thyroid hormone receptor-β analogues for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). Journal of Hepatology (2024).
- Relationship between Hypothyroidism and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis. Frontiers in Endocrinology (2017).
- Repair-Related Activation of Hedgehog Signaling in Stromal Cells Promotes Intrahepatic Hypothyroidism. Endocrinology (2014).
- Activation of thyroid hormone receptor‐β improved disease activity and metabolism independent of body weight in a mouse model of non‐alcoholic steatohepatitis and fibrosis. British Journal of Pharmacology (2021).
- Hypothyroidism-Associated Dyslipidemia: Potential Molecular Mechanisms Leading to NAFLD. International Journal of Molecular Sciences (2021).
- Thyroid hormone-mediated autophagy and mitochondrial turnover in NAFLD. Cell & Bioscience (2016).
- Benefits of Levothyroxine Replacement Therapy on Nonalcoholic Fatty Liver Disease in Subclinical Hypothyroidism Patients. International Journal of Endocrinology (2017).
About these summaries
This Nature Research Intelligence Topic summary is created with the cited references and a large language model. We take care to ground generated text with facts, and have systems in place to gain human feedback on the overall quality of the process in line with our AI principles. We strive to create accurate and useful summaries for people unfamiliar with the research topic and that supports this goal. These pages are a beta release and will be updated as we learn how best to help people gain value from a research topic summary.
Turn complex research questions into confident strategic decisions
When you're under pressure to set direction, justify investment, or understand your competitive position, you need more than raw data — you need trusted insights you can act on.
Benchmark your performance against global peers using robust, methodologically sound analysis.
Combine quantitative metrics with qualitative expert insight to uncover strengths, gaps and emerging opportunities.
Gain tailored, decision-ready recommendations aligned to your strategic priorities.
Talk to us to learn more about our data dashboards and bespoke strategy reports.
Grow research skills, confidence and careers with training built for every stage of the research lifecycle.
Developed with Nature Portfolio journal Editors and internationally renowned experts. Discover three ways to learn:
Self-paced, online courses in convenient bite-sized units, covering key skills across scientific writing, publishing, grant writing, data analysis, and more.
Expert trainer-led workshops with hands-on exercises and real-time feedback across core research skills, delivered via interactive group sessions.
Editor-led workshops combining core principles in writing and publishing, personalised 1:1 feedback from Nature Portfolio Editors and hands-on exercises.
Explore course catalogues and workshop agendas, enquire about the options or request institutional pricing.