**6. GH/IGF-1 and anthropometric characteristics of children with cholestatic diseases**

Children suffering from congenital hepatobiliary diseases have multiple and various homeostasis disorders, largely due to a violation of the key functions of the liver—synthesizing, detoxifying, regulatory, etc.—which ultimately lead to growth retardation and underweight.

In the patients before LT, the average body height was 71.2 ± 8.2 cm, and body mass was 7.9 ± 2.3 kg. Comparison of average height and weight in the study group with reference values for healthy children of the same age (mean age, 11 months) showed that the average height of the recipients was significantly lower than the

average reference value for healthy children according to World Health Organization (WHO) [55]—75 ± 6 cm, p = 0.00, and the average body mass of the recipients was significantly lower than reference values - 9.5 ± 2 kg, *p* = 0.00.

It should be noted that a correct comparison of anthropometric indicators of the study group with healthy patients is a difficult task due to the absence of a group of healthy children of the same ethnic group that is similar in age and sex. Therefore, the authors consider it possible to compare the histogram of the distribution of a trait with a normal distribution curve superimposed on a similar range of an anthropometric indicator (**Figure 5**).

**Figure 5.** *Histogram of the distribution of body height (A) and body mass (B) of children with ESLD in comparison with the normal distribution curve.*

*Growth Hormone and Insulin-like Growth Factor-1 in Children with Cholestatic Diseases… DOI: http://dx.doi.org/10.5772/intechopen.108301*

The figure shows that the histograms of body height and body mass distribution of in children with ESLD differ significantly from the normal distribution curves and are shifted to lower values.

Thus, in the examined group of children with ESLD, anthropometric indicators are lower than the values typical for healthy children of the same age. Obviously, the low body height and body mass of patients are associated with ESLD.

The Pediatric End-stage Liver Disease (PELD) scale was used to assess the relative severity of liver disease. This scale is used to evaluate the probable 90-day survival of patients awaiting LT and was developed to objectively prioritize LT candidates in children. Like the Model End-stage Liver Disease (MELD) score, the PELD score was derived from biological markers of liver function (albumin, bilirubin, and international normalized prothrombin time ratio) and growth retardation [56, 57].

The PELD score, which reflects the severity of liver disease, averaged 19.0 ± 8.2 (median, 18.0; range, 0 to 51) in the study group (**Figure 6**).

The distribution histogram of the PELD score in the examined children shows that in most patients, the score ranges from 10 to 25 and indicates that they have severe liver failure.

To assess the relationship between the severity of liver failure and the anthropometric parameters of the liver recipients, a correlation analysis was carried out between the PELD scores and the body height or body mass of the patients (**Figure 7**).

The dependencies presented in the graphs indicate that patients' height and weight, determined before transplantation, significantly correlate with the PELD score. The higher the PELD score in patients before radical treatment of the underlying disease—liver fragment transplantation—the lower the level of anthropometric parameters (body mass and height).

The obtained result suggests that, along with other changes, there may be impairment of hormonal growth regulation in this group of children. The most important growth regulators are GH produced by the pituitary gland and IGF-1 synthesized in

**Figure 6.** *Histogram of the distribution of PELD score in children with ESLD.*

**Figure 7.** *Correlation of PELD score with body height (A) and body mass (B) of pediatric liver recipients.*

the liver. Comparative analysis of GH levels in patients before LT and healthy children of the same age indicates a significant difference in the indicator (**Figure 8**).

The median plasma GH level of children with ESLD was 4.3 (1.6–7.2) ng/ml and was significantly higher than in healthy children of the same age—1.2 (0.3–2.4) ng/ ml, *p* = 0.001. Thus, there is a paradoxical situation when high GH levels in children with ESLD are combined with growth retardation and weight loss.

A comparative analysis of IGF-1 levels in patients before LT and healthy children of the same age also showed significant differences (**Figure 9**).

The median IGF-1 level in children with liver failure was 7.9 (0.0–25.1) ng/ml and was significantly lower than in healthy children: 38.0 (26.9–56.5) ng/ml, *p* = 0.001;

*Growth Hormone and Insulin-like Growth Factor-1 in Children with Cholestatic Diseases… DOI: http://dx.doi.org/10.5772/intechopen.108301*

**Figure 8.** *The level of GH in the blood of healthy children and patients with ESLD, \* - p < 0.05.*

#### **Figure 9.**

*The level of IGF-1 in the blood of healthy children and patients with ESLD, \* - p < 0.05.*

this is consistent with the literature data and is associated with the inability of the damaged liver to produce this growth regulator [58, 59]. Significantly low level of IGF-1 in liver recipients, obviously, reflects impaired synthesis and production of IGF-1 in the liver and explains the high level of GH in the blood.

Correlation analysis between GH and IGF-1 levels in children before transplantation revealed no significant relationship between hormone levels (**Figure 10**).

The analysis confirms that in children with ESLD, there is a violation of the relationship between GH and IGF-1 concentrations in the blood.

To characterize the hormonal regulation of anthropometric parameters and liver function, we analyzed the correlations between the GH and IGF-1 levels in children with height, body mass, and PELD scores (**Table 2**).

**Figure 10.** *Correlation between IGF-1 and GH blood plasma levels in children with ESLD.*


#### **Table 2.**

*Correlation of levels of GH (GH) and IGF-1 in the blood plasma of recipients with anthropometric parameters and the value of the PELD index before LT.*

The analysis revealed no statistically significant associations between GH levels and body height, body mass, or PELD score. Whereas IGF-1 concentrations in the blood were significantly associated with body height and body mass (*p* = 0.001), but not with PELD score.

The result obtained shows that in children with ESLD, their body height and body mass are not associated with plasma GH levels, while IGF-1 levels correlate with these anthropometric characteristics. In the study group, no correlation between hormone levels and ESLD was found, which is inconsistent with an earlier study that showed a relationship between GH levels and PELD score [60, 61]. This can be explained by many factors, in particular, differences in the structure of the incidence and degree of liver damage in patients in the studied samples.
