Growth factors in children with end-stage liver disease before and after liver transplantation: a review

Growth failure is a common observation in children with end-stage liver disease (ESLD). The liver is an important endocrine organ producing potent anabolic growth factors such as IGF-I (insulin-like growth factor-I) and its major binding-proteins, called IGFBP-1, -2 and -3. Circulating IGF-I and IGFBP-3 levels are low in children with chronic liver failure despite increased GH secretion. This discrepancy suggests that GH resistance is present in chronic liver failure and is mainly due to the associated malnutrition. The advent of orthotopic liver transplantation (OLT) has dramatically improved the life expectancy of children with ESLD. Nevertheless, the growth of 15-20% of the children in recent studies remains poor after successful transplantation. Several factors such as age and height deficit at the time of OLT, etiology of the liver disease and graft function as well as the dose and mode of administration of glucocorticoids have been implicated in the lack of complete catch-up growth following surgery. Few studies have explored the possibility that anomalies in the GH-IGF-I cascade could explain growth retardation. However, it is unlikely that major anomalies of the GH-IGF-I axis contribute to impaired growth. Treatment with GH alone or in combination with IGF-I before or after OLT may improve the growth of children. Randomized multi-center studies are needed to address this issue.