Insulin-like growth factor I (IGF-I) replacement therapy increases albumin concentration in liver cirrhosis: results of a pilot randomized controlled clinical trial.
OBJECTIVE
Insulin-like growth factor I (IGF-I) is an anabolic hormone synthesized in the liver whose levels decrease sharply in liver cirrhosis.


METHODS
We conducted a randomized double-blind placebo-controlled clinical trial to evaluate the effect of subcutaneous administration of IGF-I (20 microg/kg/day with dose escalation to 50-100 microg/kg/day) for 4 months in patients with alcoholic or primary biliary cirrhosis (PBC) and subnormal IGF-I levels. Eight alcoholics and one PBC entered the placebo group and seven alcoholics and two PBC the treatment group. Biochemistry, body composition, muscle mass and strength, and resting energy expenditure (REE) were evaluated.


RESULTS
Total serum IGF-I and IGF-I/IGFBP-3 ratio (a surrogate marker of IGF-I biovailability) increased in the treatment group but IGF-I values still remained below normal limits in the treated patients. No differences were observed in body composition, muscle strength or muscle mass between groups. However, IGF-I therapy increased significantly serum albumin (P = 0.038) and this improvement correlated positively with variation of IGF-I/IGFBP-3 ratio. IGF-I treatment also tended to increase REE (P = 0.085); this difference was significant (P = 0.049) in the subgroup of alcoholic patients.


CONCLUSIONS
A short course of IGF-I increased albumin levels and tended to improve energy metabolism in liver cirrhosis. These findings warrant larger clinical trials to assess the clinical benefit of IGF-I in cirrhotic patients.
Conchillo
Mariam
M
Department of Medicine and Liver Unit, Clinica Universitaria, Medical School and Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
de Knegt
Robert J
RJ
Payeras
Marina
M
Quiroga
Jorge
J
Sangro
Bruno
B
Herrero
Jose-Ignacio
JI
Castilla-Cortazar
Inma
I
Frystyk
Jan
J
Flyvbjerg
Allan
A
Yoshizawa
Carl
C
Jansen
Peter L M
PL
Scharschmidt
Bruce
B
Prieto
Jesús
J
D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000188:drug therapy*; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011994:Recombinant Proteins / Q000627:therapeutic use; D012709:Serum Albumin / Q000187:drug effects / Q000378:metabolism*
D018972:Insulin-Like Growth Factor Binding Protein 3; D010919:Placebos; D011994:Recombinant Proteins; D012709:Serum Albumin; D007334:Insulin-Like Growth Factor I