Insulin-like growth factor I (IGF-I) is a polypeptide hormone secreted
by multiple tissues in response to growth hormone (GH). It
is partly responsible for GH activity, and also has glucose-lowering
and anabolizing effects. Ninety percent of circulating IGF-I originates
in the liver and has autocrine, paracrine, and endocrine effects,
the latter on multiple tissues. Liver cirrhosis results in a progressive
decline of hepatic IGF-I output, and this factor may
become undetectable in advanced disease. Some cirrhosis complications,
mainly those nutritional and metabolic in nature (insuline
resistance, malnutrition, osteopenia, hypogonadism, intestinal disorders),
may be at least partly related to this IGF-I deficiency, since
some IGF-I effects represent a reverse image of cirrhosis complications.
Despite this, IGF-I replacement therapy has been never
suggested for cirrhosis. A number of experimental studies in cirrhotic
rats showed that therapy using low-dose recombinant IGF-I
exerts two types of effect on experimental cirrhosis: a) liver improvement
driven by improved hepatocellular function, portal hypertension,
and liver fibrosis; and b) cirrhosis-related extrahepatic disorder
improvement driven by improved food efficiency, muscle
mass, bone mass, gonadal function and structure, and intestinal
function and structure, with a normalization of sugar and amino
acid malabsorption, and improved intstinal barrier function, manifested
by reduced endotoxemia and bacterial translocation. Subsequently,
the first randomized, double-blind, placebo-controlled, pilot
clinical trial in a small number of cirrhotic patients showed
increased serum albumin and improved energy metabolism as a
result of IGF-I use. Further clinical trials are needed to identify adequate
IGF-I doses, administration duration and frequency, and the
subgroup of cirrhotic patients who will benefit most from this replacement
therapy