**4. GH/IGF-1 in liver diseases**

IGF-1 synthesis by hepatocytes is impaired in liver diseases. This leads to reduced IGF-1 levels and, according to the principle of negative feedback, leads to increased GH secretion. Despite the high serum GH levels in patients with chronic liver diseases, low IGF-1 levels can also be the result of hepatocyte resistance to GH [37, 38]. It is assumed that metabolic disorders—insulin resistance, malnutrition, osteopenia, etc.—often found in patients with liver diseases are associated with impaired neurohumoral regulation and are caused by IGF-1 deficiency [39–41].

The degree of decrease in IGF-1 levels in patients with chronic liver diseases correlates with the severity of hepatocyte dysfunction [36, 42]. Introduction of recombinant IGF-1 stops liver fibrous degeneration [43, 44]. In an animal experiment with nonalcoholic steatohepatitis (NASH), recombinant IGF-1 was shown to improve liver function in cirrhosis. Also in the experiment, it was found that the degree of hepatic ischemia-reperfusion injury is less at higher IGF-1 levels [45, 46]. Experimental studies suggest the possibility of using IGF-1 in clinical practice. Administration of recombinant IGF-1 in patients with liver cirrhosis has been shown to increase serum albumin levels and improve energy metabolism [47].

In adult patients with liver cirrhosis, GH levels are significantly higher than in healthy ones, which is associated with impaired IGF-1 synthesis by the liver in ESLD [17]. Already on day 7 following LT in adults, GH levels decrease to normal values, and those of IGF-1 increases [39].

In recent decades, there has been much focus on the study of the GH/IGF-1 axis as factors associated with longevity and quality of life [48]. It is known that life expectancy is closely related to the GH/IGF-1 axis, which may be of some importance for the development of techniques for predicting recipient and graft survival [6, 49]. It has been shown that IGF-1 can improve survival rates in rats with lipopolysaccharide/D-galactosamine-induced acute liver failure. Prophylactic administration of IGF-1 in the animals prevented an increase in bilirubin levels and transaminase activity [44].
