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OR27-2 Growth Hormone Reduces Hepatic Steatosis, Inflammation and Fibrosis in Adults with Overweight/Obesity and Nonalcoholic Fatty Liver Disease

BACKGROUND: Overweight/obesity are associated with relative growth hormone (GH) deficiency, and GH deficiency has been implicated in the development of nonalcoholic fatty liver disease (NAFLD). NAFLD and its progressive form, nonalcoholic steatohepatitis (NASH), are associated with significant morbi...

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Autores principales: Bartsch, Lea, Bredella, Miriam, Chicote, Mark L, Colling, Caitlin, Corey, Kathleen, Drescher, Hannah, Haines, Melanie, Husseini, Jad, Kimball, Allison, Lauer, Georg, Long, Michelle, Miller, Karen, Simon, Tracey, Dichtel, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9625227/
http://dx.doi.org/10.1210/jendso/bvac150.1093
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author Bartsch, Lea
Bredella, Miriam
Chicote, Mark L
Colling, Caitlin
Corey, Kathleen
Drescher, Hannah
Haines, Melanie
Husseini, Jad
Kimball, Allison
Lauer, Georg
Long, Michelle
Miller, Karen
Simon, Tracey
Dichtel, Laura
author_facet Bartsch, Lea
Bredella, Miriam
Chicote, Mark L
Colling, Caitlin
Corey, Kathleen
Drescher, Hannah
Haines, Melanie
Husseini, Jad
Kimball, Allison
Lauer, Georg
Long, Michelle
Miller, Karen
Simon, Tracey
Dichtel, Laura
author_sort Bartsch, Lea
collection PubMed
description BACKGROUND: Overweight/obesity are associated with relative growth hormone (GH) deficiency, and GH deficiency has been implicated in the development of nonalcoholic fatty liver disease (NAFLD). NAFLD and its progressive form, nonalcoholic steatohepatitis (NASH), are associated with significant morbidity and mortality, and no approved therapies currently exist. We hypothesized that GH administration would reduce hepatic steatosis, inflammation and fibrosis in individuals with overweight/obesity and NAFLD. METHODS: A randomized, double-blind, placebo-controlled trial of GH administration in adults with overweight/obesity and NAFLD was conducted (NCT02217345). Fifty-three adults ages 18-70 years with BMI ≥25 kg/m(2) and NAFLD were randomly assigned to receive daily subcutaneous GH or placebo for 6 months. Target IGF-1 was upper quartile of normal. Primary endpoints included intrahepatic lipid content (IHL) by proton magnetic resonance spectroscopy (1H-MRS) and radiographic inflammation and fibrosis by LiverMultiScan corrected T1 score (cT1). Secondary endpoints included alanine transaminase (ALT), visceral adipose tissue (VAT) by dual-energy x-ray absorptiometry (DEXA), hsCRP and HOMA-IR. Data are reported as mean ± SD. RESULTS: Forty-one subjects completed the 6-month study. Mean age (45±12 years), BMI (33±5 kg/m(2)), sex distribution (50% female) and baseline IHL (21.4±14.5%) did not differ between the GH and placebo groups. Over the 6-month study period, there was no difference in change in weight between the groups (GH -0.7±3.8% and placebo -0.6±4.0%, p=0.7). Change in absolute percent IHL was significantly greater in the GH vs placebo group (-5.1±10.5% vs 3.8±6.9%, p=0.003), resulting in a net treatment effect of an 8.9% reduction in IHL (95% CI 3.3-14.6%). Improvements in serum ALT (-10±13 IU/L vs -2±12 IU/L, p=0.009) and cT1 score (-11±63 ms vs 27±57 ms, p=0.037) were greater in the GH vs placebo group. There were also significant reductions in DEXA VAT area (-10±9 cm(2) vs 0±20 cm(2), p=0.050) and hsCRP (-0.8±0.9 mg/dL vs -0.3±1.7 mg/dL, p=0.017) in the GH vs placebo group. In multivariable models controlling for age, sex, change in weight and change in HOMA-IR, significant effects of GH vs placebo were observed on IHL (p=0.012) and ALT (p=0.015) with a trend towards improvement in cT1 score (p=0.088). In a secondary analysis excluding all subjects with >3% weight loss, which has been shown to independently impact NAFLD outcomes, there were significant improvements in IHL (p=0.001), ALT (p=0.040) and cT1 score (p=0.050) in the GH vs placebo group. No subjects were discontinued due to hyperglycemia (fasting glucose ≥126 mg/dL or HbA1c ≥6.5%). Mild edema was the only treatment-emergent side effect that had a significantly greater incidence in the GH vs placebo group (19% vs 0%, p=0.048). CONCLUSION: GH administration reduces hepatic steatosis and markers of hepatic inflammation and fibrosis in adults with overweight/obesity and NAFLD. The GH/IGF-1 axis may offer targetable therapeutic options for NAFLD/NASH. Presentation: Tuesday, June 14, 2022 10:00 a.m. - 10:15 a.m.
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spelling pubmed-96252272022-11-14 OR27-2 Growth Hormone Reduces Hepatic Steatosis, Inflammation and Fibrosis in Adults with Overweight/Obesity and Nonalcoholic Fatty Liver Disease Bartsch, Lea Bredella, Miriam Chicote, Mark L Colling, Caitlin Corey, Kathleen Drescher, Hannah Haines, Melanie Husseini, Jad Kimball, Allison Lauer, Georg Long, Michelle Miller, Karen Simon, Tracey Dichtel, Laura J Endocr Soc Neuroendocrinology and Pituitary BACKGROUND: Overweight/obesity are associated with relative growth hormone (GH) deficiency, and GH deficiency has been implicated in the development of nonalcoholic fatty liver disease (NAFLD). NAFLD and its progressive form, nonalcoholic steatohepatitis (NASH), are associated with significant morbidity and mortality, and no approved therapies currently exist. We hypothesized that GH administration would reduce hepatic steatosis, inflammation and fibrosis in individuals with overweight/obesity and NAFLD. METHODS: A randomized, double-blind, placebo-controlled trial of GH administration in adults with overweight/obesity and NAFLD was conducted (NCT02217345). Fifty-three adults ages 18-70 years with BMI ≥25 kg/m(2) and NAFLD were randomly assigned to receive daily subcutaneous GH or placebo for 6 months. Target IGF-1 was upper quartile of normal. Primary endpoints included intrahepatic lipid content (IHL) by proton magnetic resonance spectroscopy (1H-MRS) and radiographic inflammation and fibrosis by LiverMultiScan corrected T1 score (cT1). Secondary endpoints included alanine transaminase (ALT), visceral adipose tissue (VAT) by dual-energy x-ray absorptiometry (DEXA), hsCRP and HOMA-IR. Data are reported as mean ± SD. RESULTS: Forty-one subjects completed the 6-month study. Mean age (45±12 years), BMI (33±5 kg/m(2)), sex distribution (50% female) and baseline IHL (21.4±14.5%) did not differ between the GH and placebo groups. Over the 6-month study period, there was no difference in change in weight between the groups (GH -0.7±3.8% and placebo -0.6±4.0%, p=0.7). Change in absolute percent IHL was significantly greater in the GH vs placebo group (-5.1±10.5% vs 3.8±6.9%, p=0.003), resulting in a net treatment effect of an 8.9% reduction in IHL (95% CI 3.3-14.6%). Improvements in serum ALT (-10±13 IU/L vs -2±12 IU/L, p=0.009) and cT1 score (-11±63 ms vs 27±57 ms, p=0.037) were greater in the GH vs placebo group. There were also significant reductions in DEXA VAT area (-10±9 cm(2) vs 0±20 cm(2), p=0.050) and hsCRP (-0.8±0.9 mg/dL vs -0.3±1.7 mg/dL, p=0.017) in the GH vs placebo group. In multivariable models controlling for age, sex, change in weight and change in HOMA-IR, significant effects of GH vs placebo were observed on IHL (p=0.012) and ALT (p=0.015) with a trend towards improvement in cT1 score (p=0.088). In a secondary analysis excluding all subjects with >3% weight loss, which has been shown to independently impact NAFLD outcomes, there were significant improvements in IHL (p=0.001), ALT (p=0.040) and cT1 score (p=0.050) in the GH vs placebo group. No subjects were discontinued due to hyperglycemia (fasting glucose ≥126 mg/dL or HbA1c ≥6.5%). Mild edema was the only treatment-emergent side effect that had a significantly greater incidence in the GH vs placebo group (19% vs 0%, p=0.048). CONCLUSION: GH administration reduces hepatic steatosis and markers of hepatic inflammation and fibrosis in adults with overweight/obesity and NAFLD. The GH/IGF-1 axis may offer targetable therapeutic options for NAFLD/NASH. Presentation: Tuesday, June 14, 2022 10:00 a.m. - 10:15 a.m. Oxford University Press 2022-11-01 /pmc/articles/PMC9625227/ http://dx.doi.org/10.1210/jendso/bvac150.1093 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Neuroendocrinology and Pituitary
Bartsch, Lea
Bredella, Miriam
Chicote, Mark L
Colling, Caitlin
Corey, Kathleen
Drescher, Hannah
Haines, Melanie
Husseini, Jad
Kimball, Allison
Lauer, Georg
Long, Michelle
Miller, Karen
Simon, Tracey
Dichtel, Laura
OR27-2 Growth Hormone Reduces Hepatic Steatosis, Inflammation and Fibrosis in Adults with Overweight/Obesity and Nonalcoholic Fatty Liver Disease
title OR27-2 Growth Hormone Reduces Hepatic Steatosis, Inflammation and Fibrosis in Adults with Overweight/Obesity and Nonalcoholic Fatty Liver Disease
title_full OR27-2 Growth Hormone Reduces Hepatic Steatosis, Inflammation and Fibrosis in Adults with Overweight/Obesity and Nonalcoholic Fatty Liver Disease
title_fullStr OR27-2 Growth Hormone Reduces Hepatic Steatosis, Inflammation and Fibrosis in Adults with Overweight/Obesity and Nonalcoholic Fatty Liver Disease
title_full_unstemmed OR27-2 Growth Hormone Reduces Hepatic Steatosis, Inflammation and Fibrosis in Adults with Overweight/Obesity and Nonalcoholic Fatty Liver Disease
title_short OR27-2 Growth Hormone Reduces Hepatic Steatosis, Inflammation and Fibrosis in Adults with Overweight/Obesity and Nonalcoholic Fatty Liver Disease
title_sort or27-2 growth hormone reduces hepatic steatosis, inflammation and fibrosis in adults with overweight/obesity and nonalcoholic fatty liver disease
topic Neuroendocrinology and Pituitary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9625227/
http://dx.doi.org/10.1210/jendso/bvac150.1093
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