**9. Relationship between GH/IGF-1 levels and anthropometric characteristics of recipients after LT**

Analysis of changes in the anthropometric parameters of the pediatric recipients was carried out 1 year after LT, because 1 month after the operation, these indicators practically do not differ from preoperative ones.

One year after transplantation, the average height (82.1 ± 7.6 cm) and body mass (11.5 ± 2.2 kg) in the examined group were significantly higher than before LT (*p* = 0.00 for both parameters). **Figure 18** shows the change in the histogram of the distribution of height and body mass of the examined children one year after LT.

The results presented in the histogram show that the children's height and weight change a year after LT, close to the normal distribution curve.

Comparison of the average height and body mass in the study group with the reference values for healthy children of the same age (mean age, 23 months) showed that the body mass of the recipients did not significantly differ from the reference values (12 ± 2 kg), p = 0.06.

The average height of the recipients was still significantly below the average reference value for healthy children according to WHO standards (87 ± 7 cm), *p* = 0.00 [55].

Currently, there are no published studies of long-term follow-up of the anthropometric parameters of liver transplant pediatric recipients, and therefore, it is difficult to assess how fully their growth is restored in the long-term post-transplant period. For example, it has been found that for child kidney recipients, there is a problem of growth retardation both before and after transplantation, which is associated with many reasons, including taking immunosuppressants. For such patients, recommendations have been developed on how to correct growth retardation by taking recombinant GH [63].

As already noted, we compared the anthropometric indicators of the study group with healthy children by comparing the histogram of the distribution of height and body mass with a normal distribution curve superimposed on a similar range of the anthropometric indicator (**Figure 19**).

An analysis of the relationship between GH/IGF-1 levels and anthropometric parameters 1 year after LT showed that GH levels significantly correlate with body mass (r = −0.27, *p* = 0.046)—the lower the plasma GH level, the greater the body mass. The correlation of GH levels with patients' height was also negative, but did not reach statistical significance (r = −0.20, *p* = 0.143). The correlation of IGF-1 content in the blood with the height (r = 0.19, *p* = 0.055) and body mass of patients (r = 0.18,

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

#### **Figure 18.**

*Change in the histogram of the distribution of height (A) and body mass (B) of recipient children 1 year after LT.*

*p* = 0.074) was positive, but did not reach statistical significance. The described relationships reflect the restoration of the physiological regulation of anthropometric parameters in children after LT due to the restoration of IGF-1 production by the graft and provision of GH bioavailability.

A correlation analysis was carried out to assess the relationship between GH and IGF-1 levels in the blood of children after LT. It revealed the restoration of the relationship between the levels of hormones in pediatric recipients already a month after

**Figure 19.**

*Histograms of the distribution of height (A) and body mass (B) of recipient children one year after LT in comparison with the normal distribution curve.*

LT (r = −0.28, p = 0.011); the correlation strength increased a year after LT: r = −0.47, p = 0.01 (**Figure 20**).

The presented results show that in pediatric recipients a year after LT, a statistically significant negative correlation is observed between the plasma GH and IGF-1 levels, which indicates normalization of the relationship between the hormones and normalization of the regulatory mechanisms of anthropometric characteristics in the children. The IGF-1-to-GH ratio can serve as a kind of integral indicator of such normalization.

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

**Figure 20.** *Correlation of IGF-1 and GH levels in children 1 year after LT.*

Analysis before and after LT showed that this ratio increased significantly after LT (**Figure 21**).

Before LT, the IGF-1-to-GH ratio was 5.5 ± 4.2 and was significantly lower than that in healthy children - 37.1 ± 18.4 (*p* = 0.001); a month later, this parameter had increased by almost an order of magnitude, reaching 62.2 ± 41.0 (*p* = 0.001), and a year later, it had decreased to 32.6 ± 21.8 and did not differ from that in healthy children (*p* = 0.98), but was higher than before transplantation (*p* = 0.002). The data obtained suggest that mutual regulation of the GR/IGF-1 axis is restored 1 year after LT.

Obviously, normalization of the feedback between the GH and IGF-1 levels a year after LT is an indicator of the restoration of the normal ratio of the components of the central and peripheral growth regulation system and is a consequence of the restoration of liver function.

Plasma GH and IGF-1 levels not only depend on liver function, but also largely determine its condition and can be considered as indicators of liver function in patients with hepatobiliary diseases. Changes in these levels after LT can serve as an objective indicator of the degree of normalization of the synthetic function of the graft and restoration of neurohumoral regulation of the body of pediatric liver recipients.

Separate long-term post-transplant follow-up of pediatric liver recipients shows that with good graft function, the anthropometric characteristics of children can be fully restored and do not differ from those of healthy children of the same age.

**Figure 22** shows a photo of patient P. (in the center outlined by a dotted line) with her classmates 7 years after LT. It can be seen that her height is practically the same as that of her peers.

#### **Figure 21.**

*The ratio of IGF-1/GH levels in pediatric recipients before, 1 month and 1 year after LT.*

**Figure 22.** *Patient P., 7 years after LT.*

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

This study has revealed that the GH/IGF-1 axis plays a critical role in the pathogenesis of ESLD in pediatric patients. Children with ESLD have high PELD score, growth retardation, and decreased body mass. Their serum GH levels are much higher than in healthy children, while IGF-1 levels are lower than in healthy children. After LT, the GH/IGF-1 axis recovers, improving anthropometric parameters in pediatric recipients. Result of the study suggests that the GH/IGF-1 axis is of clinical significance in pediatric liver recipients. The GH/IGF-1 levels and the IGF-1-to-GH ratio can reflect liver graft function.
