Growth hormone reduces liver fat, inflammation in adults with NAFLD
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ATLANTA — Adults with overweight or obesity and nonalcoholic fatty liver disease, or NAFLD, had a significant reduction in liver fat and inflammation with daily subcutaneous growth hormone administration, according to a speaker.
“NAFLD is highly prevalent, poorly understood and still has no FDA-approved treatments,” Laura Dichtel, MD, MHS, assistant professor in the neuroendocrine unit of Massachusetts General Hospital and Harvard Medical School, said during a presentation at ENDO 2022. “We demonstrated that growth hormone administration improved NAFLD in adults with overweight and obesity. The mechanisms underlying the improvement in NAFLD with growth hormone may lead to novel therapeutic targets, which are greatly needed.”
Dichtel and colleagues conducted a randomized, double-blind placebo-controlled trial with 53 adults aged 18 to 70 years who had a BMI of 25 kg/m2 or higher, an insulin-like growth factor 1 level below the third quartile for their age, and imaging or histologically confirmed NAFLD. Participants were randomly assigned to receive subcutaneous growth hormone or placebo daily for 6 months. Primary endpoints were change in intrahepatic lipid content as measured by proton magnetic resonance spectroscopy and change in hepatic inflammation and fibrosis as measured by LiverMultiScan corrected T1 score. Secondary endpoints included alanine transaminase, body composition measured by DXA scan, fasting glucose, HbA1c, homeostasis model assessment for insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein.
Of the 53 adults enrolled, 41 completed the trial, including 20 receiving growth hormone and 21 receiving placebo. There were no significant differences in age, BMI, gender distribution or baseline liver content between the two groups. There was also no difference in BMI change between the growth hormone and placebo groups at 6 months.
“This is important because as little as 3% to 5% weight loss can improve NAFLD,” Dichtel said. “This could be a substantial confounder in our study.”
The growth hormone group had an absolute reduction of 5.1% in liver fat at 6 months compared with a 3.8% increase in the placebo group, for a net treatment reduction of 8.9% (P = .003). The growth hormone group also had a reduction in radiographic inflammation and fibrosis, whereas there was an increase in inflammation in the placebo group (P = .037).
The growth hormone group had significantly greater reductions in serum alanine transaminase (–10 IU/L vs. –2IU/L; P = .009), visceral adipose tissue (–10 cm2 vs. 0 cm2; P = .05), and high-sensitivity C-reactive protein (–0.8 mg/dL vs. –0.3 mg/dL; P = .017) compared with placebo. Significant improvements in liver fat and alanine transaminase with growth hormone were also observed in a model controlling for age, gender, change in weight and change in HOMA-IR. In a model excluding participants with 3% weight loss or more, the growth hormone group had significant reductions in liver fat, liver inflammation and alanine transaminase compared with placebo.
No serious adverse events related to treatment occurred during the study. No participants developed hyperglycemia and there were no differences in change in fasting glucose, HbA1c or HOMA-IR between the treatment and placebo groups.
Dichtel said future research on the mechanisms behind growth hormone’s impact on NAFLD should be explored to discover more possible therapeutic options for the disease.
“There are some mouse models that suggest growth hormone regulates de novo lipogenesis,” Dichtel said during a question-and-answer session following the presentation. “I had a pilot liver substudy and was able to biopsy a subset of these individual pre- and post-growth hormone. We’re looking at both bulk and single-cell RNA-sequencing that we collected during this time to try and figure out mechanisms.”
Perspective
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Scott D. Isaacs, MD, FACE, FACP
The global prevalence of NAFLD has risen substantially in parallel with the obesity pandemic, making it the leading cause of chronic liver disease. NAFLD is closely associated with visceral adiposity, insulin resistance, type 2 diabetes, hypertension and atherogenic dyslipidemia. Clinical studies have shown that serum insulin-like growth factor-1 and growth hormone levels are lower in patients with NAFLD, and patients with growth hormone deficiency have a higher prevalence of NAFLD. Observational studies have found that growth hormone treatment in adults with growth hormone deficiency led to reduction of liver enzymes, improved histology, decreased hepatic fat and visceral fat and improved insulin sensitivity.
Dichtel and colleagues performed a randomized, double-blind, placebo-controlled trial of growth hormone treatment in 53 adults with NAFLD and insulin-like growth factor-1 below the third quartile for age. Subjects treated with growth hormone for 6 months had a 5.1% reduction in intrahepatic lipid content compared to a 3.8% increase in the placebo group. The growth hormone treatment group also showed improvements in serum alanine aminotransferase, markers of fibro-inflammation and visceral adipose tissue. There was no difference in BMI change between the growth hormone and placebo groups. The authors concluded that growth hormone treatment reduces liver fat and fibro-inflammation making it a potential therapeutic option for NAFLD. Larger and longer studies are needed to assess the safety, efficacy, and long-term effects of growth hormone therapy in NAFLD.
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Dichtel L, et al. OR27. Presented at: ENDO annual meeting; June 11-14; Atlanta (hybrid meeting).
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