Growth hormone lowers liver fat for adults with obesity, steatotic liver disease
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Key takeaways:
- Adults with liver disease receiving GH vs. placebo had a greater increase in IGF-I and decrease in intrahepatic lipids.
- GH was also linked to greater reductions in hepatic steatosis and visceral adipose tissue.
Adults with overweight or obesity and metabolic dysfunction-associated steatotic liver disease had a more than 5% reduction in liver fat at 6 months with growth hormone therapy, according to findings from a randomized controlled trial.
“Specifically, GH significantly decreased liver fat and alanine aminotransferase as well as visceral adipose tissue and high sensitivity C-reactive protein,” Laura Dichtel, MD, MHS, endocrinologist and assistant professor at Harvard Medical School and the director of steatotic liver disease research in the neuroendocrine unit at Massachusetts General Hospital, told Healio. “These improvements were seen in the absence of significant weight loss, suggesting that GH acts by direct, weight-independent mechanisms to reduce liver fat and liver damage.”
Dichtel and colleagues conducted a randomized, double-blind, placebo-controlled trial at Massachusetts General Hospital where 53 adults with overweight or obesity who were diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD), which is the new nomenclature replacing nonalcoholic fatty liver disease, and had insulin-like growth factor I levels at or below the third quartile for age were enrolled (50% women; mean age, 46 years). Participants were recruited from June 2, 2017, to March 11, 2021. Participants were randomly assigned, 1:1, to daily subcutaneous GH (Genotropin, Pfizer) or matching placebo for 6 months. Intrahepatic lipid content was measured at baseline and 6 months through proton magnetic resonance spectroscopy and proton density fat fraction. Hepatic MRI and DXA scans to measure body composition were also performed at baseline and 6 months. Fasting glucose, aminotransferases and IGF-I were measured at baseline, 1 month, 2 months, 3 months and 6 months. Adverse events were collected at all study visits and by phone call 1 month after GH discontinuation.
The findings were published in The Journal of Clinical Endocrinology & Metabolism.
GH linked to greater drop in liver fat than placebo
Of the participants, 20 in the GH group and 21 in the placebo group completed the study. The treatment group had a greater increase in IGF-I compared with placebo at 6 months (mean change; 106.1 ng/mL vs. –11.8 ng/mL; P = .007). No difference in BMI or weight change was observed between the two groups.
Adults receiving GH had a greater improvement in intrahepatic lipids as measured by proton magnetic resonance spectroscopy compared with those receiving placebo (absolute change, –5.2% vs. 3.8%; P = .009). When measured by proton density fat fraction, the GH group had a 22.1% reduction in intrahepatic lipid content compared with a 42.1% increase for placebo (P = .004). The associations remained significant in multivariable models and in a sensitivity analysis that excluded adults who lost 3% or more of their body weight during the study.
GH reduces several hepatic, metabolic biomarkers
The GH group had greater reductions in hepatic steatosis (–3.4% vs. –0.4%; P = .05), serum alanine aminotransferase (–10.3 IU/L vs. –1.6 IU/L; P = .002), visceral adipose tissue (–9.9 cm2 vs. –0.1 cm2; P = .05) and mean high-sensitivity C-reactive protein (–0.8 mg/dL vs. 0.3 mg/dL; P = .003) than placebo.
No treatment-related serious adverse events or safety concerns were observed during the study.
“GH administration does have some drawbacks, such as the potential for reversible hyperglycemia and requirement of daily to weekly injections,” Dichtel said. “However, in our study of individuals with MASLD and without diabetes, we did not see an increase in glucose levels or development of diabetes. The goal of our ongoing work is to identify the mechanisms by which GH reduces liver fat and hepatocellular damage in MASLD with the goal of developing targeted and effective therapies.”
The researchers said the findings are significant due to the high prevalence of MASLD among people with obesity and the lack of treatments available for MASLD.
“Future research should focus on identifying the mechanisms of the effects of GH and IGF-I, which likely have unique and independent mechanisms to reduce hepatic steatosis and ameliorate hepatic inflammation and fibrosis,” the researchers wrote. “In addition to elucidating underlying pathophysiology of this disease process, identification of the molecular mechanisms of the GH/IGF-I axis in [MASLD] and nonalcoholic steatohepatitis has the potential to lead to the development of novel therapeutics.”
For more information:
Laura Dichtel, MD, MHS, can be reached at ldichtel@mgh.harvard.edu.
Perspective
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Scott D. Isaacs, MD, FACE, FACP
Patients with overweight or obesity often have functional growth hormone deficiency with IGF-1 levels around 25% of normal. GH administration in these patients is known to decrease visceral adipose tissue, increase lean body mass and acts as an anti-inflammatory cytokine with additional immunomodulatory properties that may be beneficial in metabolic dysfunction-associated steatotic liver disease (MASLD), which is the new nomenclature replacing nonalcoholic fatty liver disease.
In this study, Dichtel and colleagues conducted a randomized, double-blind, placebo-controlled trial of GH replacement in adults with overweight or obesity who had MASLD and had IGF-1 levels at or below the third quartile for age.
Subjects who received GH vs. placebo had a 22% relative reduction in hepatic steatosis by proton magnetic resonance spectroscopy in addition to improvements in fibro-inflammation by corrected T1 imaging (cT1), alanine transaminase, visceral adipose tissue by DEXA and high-sensitivity C-reactive protein. A sensitivity analysis that excluded subjects who lost more than 3% of body weight found that the improvements in liver parameters were independent of weight change. The decrease in visceral adipose tissue and high-sensitivity C-reactive protein suggests that GH supplementation is beneficial for MASLD by improving body composition, decreasing inflammation and improving overall metabolic health. The authors concluded that GH treatment reduces liver fat and fibro-inflammation making it a potential therapeutic option for MASLD. Larger and longer studies are needed to assess the safety, efficacy, and long-term effects of GH therapy in MASLD.
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