Journal
LIVER INTERNATIONAL
Volume 31, Issue 7, Pages 911-919Publisher
WILEY
DOI: 10.1111/j.1478-3231.2010.02428.x
Keywords
chronic liver disease; cirrhosis; growth hormone; insulin-like growth factor; malnutrition
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Funding
- Novo Nordisk Fonden [NNF11OC1015075, NNF11OC1014467] Funding Source: researchfish
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Insulin-like growth factors (IGFs) play an essential role in growth and development, as well as in the overall cellular regulation and metabolism in the human body. In chronic liver disease, IGF levels are decreased, and the circulating levels correlate to the extent of hepatocellular dysfunction. Patients with cirrhosis are characterised by a variety of metabolic disturbances, including nutritional and metabolic complications such as insulin resistance, malnutrition, osteopenia and hypogonadism, all related to IGF-I deficiency. The complex process of hepatic fibrogenesis and the systemic consequences in cirrhosis are only partly understood. Disruption of the growth hormone (GH)-IGF-I axis seems to be closely associated with the development of liver disease, and treatment with recombinant human IGF (rhIGF)-I has been shown to halt, and even reverse, the fibrotic degeneration. IGF-I in itself has a strong antifibrotic effect that acts directly through the GH/IGF system and indirectly by the regulation of hepatoprotective and profibrogenic factors. It is most likely that IGF-I deficiency contributes to the diverse metabolic complications of cirrhosis. At present, liver transplantation remains the only efficient treatment of cirrhosis, and thus new methods of managing the disease are called for. RhIGF-I supplementation and IGF-I gene therapy may represent future perspectives of treatment.
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