GH treatment in adults with chronic liver disease: a randomized, double-blind, placebo-controlled, cross-over study.
Patients with chronic liver disease (CLD) are catabolic and GH-resistant. The effects of supraphysiological recombinant human GH (rhGH; 0.2 IU.kg(-1).d(-1)) treatment in adults with CLD were assessed in a randomized, double-blind, placebo-controlled cross-over trial (4-wk dietary run-in, 4-wk treatment, and 2-wk wash-out phases). Nine adults with mild- to moderate-severity CLD participated (median age, 49 yr; three males and six females; Child's classification A in six and B in three). Biopsy-proven etiologies were: alcohol (four patients), primary biliary cirrhosis (three patients), non-A, non-B, non-C hepatitis (one patient), and cryptogenic (one patient). Treatment with rhGH increased serum IGF-I (median increase over placebo, +93 microg.liter(-1); P = 0.004), IGF-binding protein-3 (+0.9 mg.liter(-1): P = 0.004), and acid labile subunit (+10.7 nM; P = 0.004). Total body potassium (+8.0 g; P = 0.023), body weight (+1.6 kg; P = 0.008), and total body water (by bioelectrical impedance; +4.9 kg; P = 0.004) increased. Resting metabolic rate (+313 ml.kg(-1).min(-1); P = 0.004) and lipid oxidation (+1072.0 kcal.d(-1); P = 0.032) increased. Metabolic changes included increased fasting plasma glucose (+1.2 mM; P = 0.008), insulin (+33.8 mU.liter(-1); P = 0.004), C-peptide (+0.7 nM; P = 0.004), and free-fatty acids (+0.1 mEq.liter(-1); P = 0.04). Clinical side effects included worsening edema and ascites. Hepatocellular function did not change. Therefore, rhGH treatment in CLD: 1) overcame hepatic GH resistance; 2) may have improved whole-body protein catabolism; 3) increased lipolysis and lipid oxidation; 4) increased insulin resistance; and 5) had potent antinatriuretic effects. Long-term safety and efficacy require further assessment.
Wallace
Jennifer D
JD
Metabolic Research Unit, Department of Medicine, University of Queensland, Princess Alexandra Hospital, Wooloongabba, Brisbane 4102, Australia. jwallace@medicine.pa.uq.edu.au
Abbott-Johnson
Winsome J
WJ
Crawford
Darrell H G
DH
Barnard
Ross
R
Potter
Julia M
JM
Cuneo
Ross C
RC
D001769:Blood / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood; D002908:Chronic Disease; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006023:Glycoproteins / Q000097:blood; D019382:Human Growth Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008107:Liver Diseases / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use*
D002352:Carrier Proteins; D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D010919:Placebos; D011994:Recombinant Proteins; C075944:insulin-like growth factor binding protein, acid labile subunit; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I