Role of Growth Hormone Therapy in Metabolic-Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis

Abstract Multiple observation studies and meta-analysis have linked growth hormone (GH) deficiency with metabolic-dysfunction-associated steatotic liver disease (MASLD). No meta-analysis has analysed the efficacy and safety of GH therapy on different aspects of MASLD. We undertook this meta-analysis to address this gap in knowledge. Electronic databases were searched for RCTs involving patients with MASLD receiving GH therapy. Primary outcome was to evaluate changes in radiologic measures of MASLD (magnetic resonance spectroscopy (MRS) and ultrasonography) and liver enzymes. Secondary outcomes were to evaluate alterations in body composition parameters [dual-energy X-ray absorptiometry (DXA)], lipids, glycaemia and side effects. From initially searched 1047 articles, data from three RCTs (120 patients) which fulfilled all criteria were analysed. After 6 months of GH therapy in MASLD, the per cent reduction in intrahepatic lipid (MRS) was significantly higher with GH as compared to placebo [MD -5.85% (95%CI:-11.41– -0.30); P = 0.04; I 2 = 63%]. Visceral adipose tissue (VAT) area reduction (DXA) was significantly higher with GH [MD-9.94 cm 2 (95%CI:-19.04– -0.84); P = 0.03; I 2 = 0%]. Serum insulin-like growth factor-1 (IGF-1) was significantly raised in MASLD patients receiving GH as compared to placebo [MD +166.86 ng/ml (95%CI: 79.19–254.53); P < 0.0.001; I 2 = 90%]. High-sensitivity C-reactive protein (hsCRP) was significantly lower in patients receiving GH [MD -0.89 mg/L (95%CI:-1.40–-0.38); P = 0.0.0006; I 2 = 0%]. Patients receiving GH had similar changes in triglycerides [MD-1.06 mg/L (95%CI:-20.45–18.34); P = 0.91; I 2 = 15%] and fasting glucose [MD -0.56 mg/L (95%CI:-4.67–3.55); P = 0.79; I 2 = 39%]. Gamma-glutamyl transpeptidase was significantly lower in patients receiving GH [MD -7.86 U/L (95%CI:-12.46–-3.27); P = 0.0008; I 2 = 0%]. No increase in new-onset hypothyroidism was noted [OR 5.49 (95%CI: 0.25–121.18); P = 0.28]. Short-term 6-month GH therapy in MASLD is associated with a significant reduction in intrahepatic lipid content, visceral adiposity, GGT and hsCRP without any increased occurrence of dysglycaemia or hypothyroidism.