Paul Manka1,2, Lars Bechmann3, Jan Best3, Svenja Sydor3, Lee C Claridge4, Jason D Coombes5,6, Ali Canbay3, Lars Moeller7, Guido Gerken8, Heiner Wedemeyer8, Wing-Kin Syn9,10,11. 1. Department of Gastroenterology and Hepatology, University Hospital Essen, Hufelandstr. 55, 45122, Essen, Germany. paul.manka@uk-essen.de. 2. Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. paul.manka@uk-essen.de. 3. Gastroenterology, Hepatology and Infectiology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany. 4. Department of Hepatology, Leeds Teaching Hospital NHS Trust, Leeds, UK. 5. Department of Inflammation Biology, Faculty of Life Sciences and Medicine, King's College London, London, UK. 6. Department of Bioengineering, California Institute for Quantitative Biosciences, University of California, Berkeley, CA, USA. 7. Department of Endocrinology, Diabetology, and Metabolism, University Hospital Essen, Essen, Germany. 8. Department of Gastroenterology and Hepatology, University Hospital Essen, Hufelandstr. 55, 45122, Essen, Germany. 9. Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. 10. Section of Gastroenterology, Ralph H Johnson Veterans Affairs Medical Center, Charleston, SC, USA. 11. Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country, UPV/EHU, Leioa, Spain.
Abstract
BACKGROUND: Thyroid hormone is critical for tissue-organ development, growth, differentiation, and metabolism. In murine models of advanced nonalcoholic steatohepatitis (NASH), the administration of T3 reduced liver triglyceride, repressed liver inflammation, and attenuated injury. In recent studies of patients with NASH, hypothyroidism was noted to be associated with more advanced NASH. These findings suggest that thyroid hormone function might be a modulator of nonalcoholic fatty liver disease (NAFLD) outcomes. AIMS: Herein, we evaluated the correlation between plasma TSH/free T3 (fT3)/free T4 (fT4) levels and (non-invasive) surrogate markers of NAFLD fibrosis. METHODS: We performed a retrospective analysis of 144 patients who were seen in our NASH outpatient clinic between 2015 and 2017. Each patient underwent a standard anthropometric assessment, laboratory and clinical evaluations, and liver stiffness measurements by transient elastography (Fibroscan). Univariate analysis and multivariate linear and logistic regression analysis were used to identify factors independently associated with NASH and advanced fibrosis. RESULTS: Low fT3 values but not TSH and fT4 were associated with higher liver stiffness and higher NAFLD fibrosis score, respectively. fT3 and TSH values correlated significantly with indices of liver disease including INR, albumin, ALT, AST, bilirubin, and platelets. In multivariate analyses, a low fT3 was independently associated with high NFS scores (OR 0.169, CI 0.05-0.54, p = 0.003) and was also associated with high liver stiffness readings (OR 0.326, CI 0.135-0.785, p = 0.001). CONCLUSION: A low-normal thyroid hormone function is predictive of NASH and advanced fibrosis and may have a pathogenic role in modulating NAFLD outcomes.
BACKGROUND: Thyroid hormone is critical for tissue-organ development, growth, differentiation, and metabolism. In murine models of advanced nonalcoholic steatohepatitis (NASH), the administration of T3 reduced liver triglyceride, repressed liver inflammation, and attenuated injury. In recent studies of patients with NASH, hypothyroidism was noted to be associated with more advanced NASH. These findings suggest that thyroid hormone function might be a modulator of nonalcoholic fatty liver disease (NAFLD) outcomes. AIMS: Herein, we evaluated the correlation between plasma TSH/free T3 (fT3)/free T4 (fT4) levels and (non-invasive) surrogate markers of NAFLD fibrosis. METHODS: We performed a retrospective analysis of 144 patients who were seen in our NASH outpatient clinic between 2015 and 2017. Each patient underwent a standard anthropometric assessment, laboratory and clinical evaluations, and liver stiffness measurements by transient elastography (Fibroscan). Univariate analysis and multivariate linear and logistic regression analysis were used to identify factors independently associated with NASH and advanced fibrosis. RESULTS: Low fT3 values but not TSH and fT4 were associated with higher liver stiffness and higher NAFLD fibrosis score, respectively. fT3 and TSH values correlated significantly with indices of liver disease including INR, albumin, ALT, AST, bilirubin, and platelets. In multivariate analyses, a low fT3 was independently associated with high NFS scores (OR 0.169, CI 0.05-0.54, p = 0.003) and was also associated with high liver stiffness readings (OR 0.326, CI 0.135-0.785, p = 0.001). CONCLUSION: A low-normal thyroid hormone function is predictive of NASH and advanced fibrosis and may have a pathogenic role in modulating NAFLD outcomes.
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