**4. Statistical analysis**

Statistical data processing was performed by the IBM SPSS Statistics 19 pack. Most quantitative values were not within the normal distribution, so nonparametric statistic methods were applied. All quantitative data were presented as M (mean),

*Shear Wave Elastography in the Assessment of Liver Changes in Children with Cystic Fibrosis DOI: http://dx.doi.org/10.5772/intechopen.103185*

**Figure 4.**

*An example of liver stiffness assessment in a child with cystic fibrosis: B-mode and two-dimensional shear wave elastography mode. The results of one of 10 measurements. Emean = 27.4 kPa. The child is 12 years old.*

m (standard error of the mean), σ (standard deviation), median (50th percentile), 25th–75th percentiles and minimum and maximum values. Quantitative parameters were compared using Mann–Whitney criterion, qualitative ones were compared using Fisher criterion of accuracy. The differences were considered significant at P ≤ 0.05.

#### **5. Results**

Two-dimensional shear wave elastography was performed in 200 (control group) conditionally healthy children aged 3 to 18 years who underwent ultrasound examination for reasons unrelated to hepatobiliary diseases. Routine ultrasound examination did not reveal any changes in the liver, spleen and gallbladder in children of the control group. The technique and results of two-dimensional liver elastography performed in healthy children of different age groups had been published by us earlier [33, 34]. Statistical processing of the results of the previous study allowed to establish the mean value of Young modulus in the group of healthy children, i.e., 5.01 ± 0.03 kPa, the median of the average Emean value was 5.00 kPa (4.70–5.38). We did not find statistically significant gender differences in liver stiffness in children of the control group [33, 34].

In the group of children with cystic fibrosis, hepatomegaly was revealed in the vast majority of children – 31 patients (96.9%), splenomegaly – in 10 patients (31.3%). In 13 children (40.6%), changes in the gallbladder were detected in the form of a wall thickening of more than 4 mm, or its decreased size. Six children had signs of portal hypertension (18.8%), which was manifested by hepatosplenomegaly, portal vein dilation with decreased linear blood flow velocity and oesophageal varices according to gastroduodenoscopy. The ultrasound picture of the liver was presented as unchanged parenchyma. Also, a diffuse or inhomogeneous increase of echogenicity,

heterogeneity of the parenchyma with a pronounced vascular pattern, cirrhotic nodes with depletion and deformation of a typical vascular tree, pronounced periportal fibrosis were determined. The elastography picture of the liver in children with cystic fibrosis was various. It was represented both by homogeneous colouring of the colour window in dark blue or blue tones, with the absence of areas of increased stiffness, in that case, the qualitative characteristics did not differ from the control group of healthy children (**Figures 1** and **2**), and also, blue-green with yellow areas, as well as red-orange colouring of the area of interest in children with pronounced ultrasound signs of cirrhotic liver changes (**Figures 3–5**).

The values of the liver parenchyma stiffness in the studied groups and subgroups are shown in **Tables 1** and **2**.

Significant differences in the values of Young modulus (Emean) were obtained when comparing the values of the study and control groups: median Emean – 6.50

#### **Figure 5.**

*An example of liver stiffness assessment in a child with cystic fibrosis: B-mode and two-dimensional shear wave elastography mode. The results of 4 measurements. Emean = 38.0 kPa. Median – 36.8 kPa. The child is 14 years old.*


#### **Table 1.**

*Stiffness (Emean, kPa) of liver parenchyma in children of the studied groups: healthy children and children with cystic fibrosis.*

*Shear Wave Elastography in the Assessment of Liver Changes in Children with Cystic Fibrosis DOI: http://dx.doi.org/10.5772/intechopen.103185*


#### **Table 2.**

*Stiffness (Emean, kPa) of liver parenchyma in children with cystic fibrosis of various severity (n = 32).*

and 5.00 kPa, interquartile range – 5.62–7.52 and 4.70–5.38 kPa, respectively (P< 0.001). Most children suffering from cystic fibrosis had some degree of change in liver stiffness. In the group of patients with cystic fibrosis, only 9 (28.1%) children had Young modulus values that did not exceed those in healthy children. Analysis of the data obtained showed that the values of Young modulus in the group of patients with a severe course of the disease was significantly higher than in patients with a moderate course of cystic fibrosis: median Emean – 7.30 and 5.90 kPa, interquartile range – 6.20–10.70 and 5.20–6.75 kPa, respectively (P< 0.002).

#### **6. Discussion**

In the available publications, we were able to find only a few works devoted to the shear wave elastography assessment of liver stiffness in a group of children suffering from cystic fibrosis. It should be noted that the paediatric age group is the most interesting for assessing liver changes since cystic fibrosis-associated liver diseases develop in early childhood, and new cases are rare after the age of 20. In 2009, P. Witters et al. [35] used transient elastography to study liver stiffness in 66 patients with cystic fibrosis [35]. The obtained elastometry findings were compared with those of a control group consisting of 59 people (98th percentile (or M + 2σ), Young modulus for children under 12 years of age was 5.63 kPa, 12 years and older – 6.50 kPa). In our study, the maximum value of 6.30 kPa (with a median of 5.00 kPa) in the control group was used as a threshold. Such clinical manifestations as hepatosplenomegaly and changes in biochemical parameters were taken into consideration in the patients of the study group. Only one patient underwent a liver biopsy. The study showed an increase in stiffness in patients with clinical manifestations, such as palpable hepatosplenomegaly (11.07 ± 5.51 kPa (n = 6) vs. 5.08 ± 3.45 kPa (n = 60), P < 0.0001), biochemical (7.40 ± 3.10 kPa (n = 7) vs. 5.42 ± 4.08 kPa (n = 59), P = 0.013) and ultrasound (8.19 ± 5.96 kPa (n = 23) vs. 4.27 ± 0.94 kPa (n = 41), P = 0.0001) signs of liver damage. The mean value of liver stiffness in children with cystic fibrosis was 5.63 ± 4.02 kPa [35]. In our study, the median of Young modulus was 6.50 kPa in patients with cystic fibrosis. We got fairly close values, although the two studies were conducted on different devices. The stage of liver fibrosis during puncture biopsy was not evaluated in both studies.

In 2012, the research group of L. Monti et al. [36] evaluated liver stiffness using shear wave point elastography in the group of 75 children with cystic fibrosis. Measurements of the shear wave velocity were carried out in the right liver lobe, followed by averaging of 10 indices. The patients underwent ultrasound examination, gastroscopy and analysis of biochemical parameters. Liver biopsy was not performed. The study found that the median shear wave velocity was significantly higher in patients with clinical, biochemical and ultrasound signs of liver damage, than in patients with their absence. The velocity increased as the signs of decompensation of portal hypertension increased, that is, with the progression of fibrous changes. The median in patients with portal hypertension, splenomegaly and oesophageal varices was 1.30, 1.54 and 1.63 m/s, respectively (P < 0.001) [36].

A study by T. Canas et al. conducted in 2015 [37] included 72 patients with cystic fibrosis aged 9 months to 18 years. The stiffness of the liver and spleen was assessed using shear wave point elastography after the routine ultrasound examination. The biopsy was not included in the protocol. As in our study, a convex sensor was used, five measurements of the shear wave velocity were carried out in the right and left liver lobes (intercostal and subcostal access) and in the spleen. The obtained data were compared with the results of the control group (n = 60). The shear wave point elastography revealed a significant increase in the shear wave velocity in patients with cystic fibrosis-associated liver disease compared with healthy children and patients with cystic fibrosis without liver involvement (P = 0.003). The diagnosis of 'cystic fibrosis-associated liver disease' was made using non-invasive Colombo criteria [18]. The threshold value of the shear wave velocity for the diagnosis of cystic fibrosisassociated liver disease was 1.27 cm/s (measurement in the right liver lobe) with 56.5 % sensitivity, 90.5% specificity, AUC 0.746 [37].

Reports on the study of liver stiffness by two-dimensional shear wave elastography using the Aixplorer device (Supersonic Imagine, France) in children suffering from cystic fibrosis could not be found. We carried out measurements on segments of the right liver lobe using a convex sensor to standardise the study protocol as the linear sensor measurements were not always considered technically possible in older children. The analysis of the data obtained by us, as well as other research groups, revealed that the indices of hepatic tissue stiffness in patients with cystic fibrosis had significantly higher values than in healthy children. Liver stiffness in children with a severe course of the disease was more apparent than in children with a moderately severe course. As the clinical, biochemical and ultrasound signs of liver damage increased, the stiffness indices accordingly increased. A clear insight into the degree of damage, stage and rate of fibrosis progression in chronic liver disease in children is important when making a comprehensive decision when to resort to surgical methods of treatment and to liver transplantation. Taking into consideration the above mentioned and based on the results of our study, we consider it appropriate to monitor the indices of Young modulus in patients with cystic fibrosis, as it enables to identify a group of children with high rates of fibrosis.
