The role of elastography in the assessment of chronic liver disease in children

Background Conventional ultrasonography is a method preferred for the investigation of chronic liver diseases in pediatric groups, as it is non-invasive, cheap, feasible and available. The purpose of this study is to present the role of Share-wave Elastography (SWE) in terms of diagnostic value in children diagnosed with “chronic liver disease.” Methods We studied patients who had been diagnosed with chronic liver disease between March 2012-September 2015, and who had undergone liver biopsy and had their pathology results, compared with 26 healthy subjects. Statistical analysis was performed with IBM SPSS Statistics for Windows, Version 20.0. “Pearson Correlation Analysis” was performed in order to measure the relationship between elastography values and Brunt level. Results This study had 107 subjects in total, consisting of 81 patients between 0–204 months of age Pearson correlation coefficient level was determined as r = 0.644. Since the correlation coefficient is positive, there is a same-directional relationship between Elastography level and Brunt degree. This means that while one of the variables is increasing, the other one will also increase. Conclusion Since it is known that development of hepatic fibrosis is a dynamic process, and that many hepatic fibrosis etiologies are known to continue throughout the course of life, the application of Real time SWE method instead of repeated liver biopsies on patients is a much simpler and smart method. Increasing the clinical use of Real Time SWE method with future studies might provide an opportunity for preventing unnecessary liver biopsies since the patients are evaluated in a shorter time and in a cost-effective manner.


Background
Chronic liver disease is a significant health issue among children and it can result in fibrosis, cirrhosis and liver failure. Since the prognosis and monitoring of these diseases are different from each other, distinguishing them is important. 1,2 . While liver needle biopsy is still recognized to be the gold standard for the assessment of liver fibrosis in the diagnosis and follow-up of chronic liver diseases, researchers tend to study non-invasive methods in the determination of liver fibrosis, as liver needle biopsy is an invasive, painful and expensive procedure, which can cause possible sampling errors and potential complications 3,4 . Conventional ultrasonography is preferred for the investigation of chronic liver diseases in children, as it is non-invasive, cheap, feasible and available. Elastography, an ultrasonographic non-invasive procedure that measures tissue stiffness 5,6 . Liver fibrosis is a result of chronic damage, and attacks and remissions throughout the course of the disease trigger the formation of fibrosis. Apart from being a direct indicator of liver damage, fibrosis has an important role in the development of hepatocyte dysfunction and portal hypertension. In a clin-ical aspect, knowing the state and progress of fibrosis is important in the assessment of treatment response for the severity and the prognosis of the disease. The degree of fibrosis in the liver is important in the determination of prognosis, and management of the process in chronic liver disease. Patients with fibrosis benefit from treatment in case of early diagnosis 7,8 . Shear-Wave Elastography is a non-invasive method, and the purpose of this study was to compare Real Time Shear-Wave Elastography method, with histopathological Brunt scoring systems, which are recognized to be the diagnostic reference method, and to determine its suitability for routine use in cases with chronic liver disease in the assessment of liver fibrosis. In summary, the purpose of this study was to present the role of Share-wave Elastography, in terms of diagnostic value in children diagnosed with "Chronic Liver Disease" 9,10 .

Patients and methods
We studied 107 subjects in total. These consisted of 81 patients aged between 0-204 months, and who attended Istanbul University Cerrahpaşa Faculty of Medicine Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition between March 2012-September 2015. They were diagnosed with chronic liver disease, underwent liver biopsy and had their pathology results. We also studied 26 healthy cases.
"Real time Shear-wave Elastography" was performed on patients in the study groups at Istanbul University Cerrahpaşa Faculty of Medicine Department of Radiology within the same period, and all results were evaluated retrospectively. Patients older than 204 months, those who did not undergo liver biopsy and "Real time Shear-wave Elastography" procedure were excluded. The control group was selected from the children who had attended for reasons other than liver disease and Medical Ultrasonography.
Patients were asked to not eat anything, starting from at least 8 hours before the procedure, due to the fact that hepatobiliary ultra-sonography was applied before Real Time Shear-Wave Elastography procedure and B-mode imaging was used as a guide during Real Time Shear-Wave Elastography. No drugs were administered to patients for imaging throughout the process, and no radiation administration was performed since this method is performed with an ultrasound device. In the procedure, first B-mode imaging was performed for liver imaging, and then it was switched to elastography mode in synchronization with B-mode imaging. During elastography procedure, shearwaves were formed with successive pressures applied to the skin with the ultrasound probe. Statistical analysis was performed with IBM SPSS Statistics for Windows, Version 21.0 IBM Corp., Armonk, NY; licence number: eb3501007d98f50286ae. "Receiver Operating Characteristics Curve ROC"method was used in order to determine the cut-off value. The diagnostic performance of elastography and the distinction between histopathological fibrosis stages were evaluated with respect to the areas under the ROC curve AUROC: areas under the ROC curve, accuracy. Since the data is distributed homogeneously, "Independent Sample -t test" and "One-way ANOVA" analyses were used for the comparison between groups. A p value of < 0.05 was assumed to be statistically significant. "Pearson Correlation Analysis" was performed in order to measure the relationship between elastography values and Brunt level. Ethical approval was obtained form Istanbul University Cerrahpaşa Faculty of Medicine Clinical Trials Ethics Committee Number: 83045809/604.01/02-394991.

Results
From the 107 subjects in total, 81 patients were diagnosed with chronic liver disease and 26 health cases. The minimum age of the patients who participated in the study was 0 months, and the maximum was 204 months. Brunt classification and elastography measurement results of patients who had undergone liver biopsy and had their pathology results are presented in Table 1.
African Health Sciences Vol 19 Issue 3, September, 2019 Patients who have F0 values in the patient group were compared with the values of control group. Since the data is distributed homogeneously, "Independent sample-t test" was applied to these groups. No significant difference was determined between these groups Sig p>0,05. Patient group was firstly subjected to "One-way ANOVA" test in order to investigate whether there was a difference between the groups with regard to a single characteristic. Since intergroup variances are distributed homogeneously, calculations were proceeded with "Posthoc Tukey" test. P< 0,05 is recognized to be significant and presented in Table 2. "Pearson Correlation Analysis" was performed in order to measure the relationship between elastography values and Brunt level. Pearson correlation coefficient level was determined as r = 0.644. Since the correlation coefficient is positive, there is a same-directional relationship between Elastography level and Brunt degree. This means that while one of the variables is increasing, the other one will also increase.

Discussion
Liver biopsy is still the the gold standard in the diagnosis and assessment of liver fibrosis 11,12 . This procedure is costly, invasive and carries risk of complications. It needs to be performed in the company of a senior physician 13 . Furthermore, there are limiting factors such as sampling errors, and differences in the assessment among pathologists who examine the biopsy material 14,15 . Ferraioli et al. 16 . established that the cut-off value of Brunt groups of F2 and above should be 7.1 kpa and above, while it should be 8.7 kpa for groups F3 and above, and 10.4 kpa for patients with F4 fibrosis. Since the patient group includes adult Hepatitis C patients in this study, it is considered that the results might be different from these findings in our study, which had children with chronic liver disease 16 . Myers et al. 17 have reported 56%-96% sensitivity and 66%-91% specificity in the determination and scoring of liver fibrosis in their multi-center study of 251 cases performed using Transient Elastography method to assess liver fibrosis in Chronic Hepatitis B, Chronic Hepatitis C and NASH patients. In our study, a high correlation was observed between elastography value and degree of degree fibrosis particularly in inflammatory processes and cholestatic diseases, while this correlation was observed to be lower in Wilson's disease, hepatosteatosis and depot diseases. The reason of the decrease in these diseases is considered to be especially due to hepatosteatosis experienced in early stage. Since there is no extensive study on depot diseases in the literature, elastography studies performed on children with depot disease will be valuable in providing important information. Unlike the single-point measurement in liver biopsy, there are advantages of Real Time SWE method such as performing measurements on numerous points in right and left lobes of liver parenchyma by placing as many ROIs as possible in liver parenchyma, and examining a larger area in the liver.

Conclusion
Since it is known that develpoment of hepatic fibrosis is a dynamic process, and that many hepatic fibrosis etiologies are known to continue throughout the course of life, the application of Real time SWE method instead of repeated liver biopsies on patients is a much simpler and smart method. Increasing the clinical use of Real Time SWE method with future studies might provide an opportunity for preventing unnecessary liver biopsies since the patients are evaluated in a shorter time and in a cost-effective manner.