Growth Hormone Administration Improves Nonalcoholic Fatty Liver Disease in Overweight/Obesity: A Randomized Trial

Abstract Context Overweight and obesity are associated with relative growth hormone (GH) deficiency, which has been implicated in the development of nonalcoholic fatty liver disease (NAFLD). NAFLD is a progressive disease without effective treatments. Objective We hypothesized that GH administration would reduce hepatic steatosis in individuals with overweight/obesity and NAFLD. Methods In this 6-month randomized, double-blind, placebo-controlled trial of low-dose GH administration, 53 adults aged 18 to 65 years with BMI ≥25 kg/m2 and NAFLD without diabetes were randomized to daily subcutaneous GH or placebo, targeting insulin-like growth factor 1 (IGF-1) to the upper normal quartile. The primary endpoint was intrahepatic lipid content (IHL) by proton magnetic resonance spectroscopy (1H-MRS) assessed before treatment and at 6 months. Results Subjects were randomly assigned to a treatment group (27 GH; 26 placebo), with 41 completers (20 GH and 21 placebo) at 6 months. Reduction in absolute % IHL by 1H-MRS was significantly greater in the GH vs placebo group (mean ± SD: −5.2 ± 10.5% vs 3.8 ± 6.9%; P = .009), resulting in a net mean treatment effect of −8.9% (95% CI, −14.5 to −3.3%). All side effects were similar between groups, except for non-clinically significant lower extremity edema, which was more frequent in the GH vs placebo group (21% vs 0%, P = .02). There were no study discontinuations due to worsening of glycemic status, and there were no significant differences in change in glycemic measures or insulin resistance between the GH and placebo groups. Conclusion GH administration reduces hepatic steatosis in adults with overweight/obesity and NAFLD without worsening glycemic measures. The GH/IGF-1 axis may lead to future therapeutic targets for NAFLD.