Observational Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2016; 22(16): 4238-4249
Published online Apr 28, 2016. doi: 10.3748/wjg.v22.i16.4238
Transient elastography compared to liver biopsy and morphometry for predicting fibrosis in pediatric chronic liver disease: Does etiology matter?
Behairy El-Sayed Behairy, Mostafa Mohamed Sira, Khaled Refat Zalata, El-Sayed Ebrahem Salama, Mohamed Ahmed Abd-Allah
Behairy El-Sayed Behairy, Mostafa Mohamed Sira, El-Sayed Ebrahem Salama, Mohamed Ahmed Abd-Allah, Department of Pediatric Hepatology, National Liver Institute, Menofiya University, Shebin El-koom 32511, Menofiya, Egypt
Khaled Refat Zalata, Department of Pathology, Faculty of Medicine, Mansura University, Dakahliya Governorate 35516, Egypt
Author contributions: Behairy BE, Sira MM, Zalata KR, Salama EE and Abd-Allah MA were involved in the study concept and design; Behairy BE, Sira MM and Abd-Allah MA were involved in recruitment of patients, clinical management, follow up and contributed to data acquisition; Sira MM performed the statistical analysis and designed the figures; Behairy BE, Sira MM, Zalata KR, Salama EE and Abd-Allah MA performed the data interpretation; Behairy BE, Sira MM, Abd-Allah MA wrote the manuscript; Zalata KR performed histopathological assessment; all the authors reviewed and agreed the final manuscript.
Supported by the National Liver Institute, Menofiya University, Egypt, No. 2011.MDT013.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of National Liver Institute, Menofiya University (Egypt).
Informed consent statement: All the legal guardians of the study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Mostafa Mohamed Sira, MD, Department of Pediatric Hepatology, National Liver Institute, Menofiya University, Gamal Abd El-Nasir, Shebin El-koom 32511, Menofiya, Egypt. msira@liver-eg.org
Telephone: +20-48-2222740 Fax: +20-48-2234586
Received: January 7, 2016
Peer-review started: January 8, 2016
First decision: February 18, 2016
Revised: March 4, 2016
Accepted: March 18, 2016
Article in press: March 18, 2016
Published online: April 28, 2016
Abstract

AIM: To evaluate transient elastography (TE) as a noninvasive tool in staging liver fibrosis compared with liver biopsy and morphometry in children with different chronic liver diseases.

METHODS: A total of 90 children [50 with chronic hepatitis C virus (HCV), 20 with autoimmune hepatitis (AIH) and 20 with Wilson disease] were included in the study and underwent liver stiffness measurement (LSM) using TE. Liver biopsies were evaluated for fibrosis, qualitatively, by Ishak score and quantitatively by fibrosis area fraction (FAF) using digital image analysis (morphometry). LSM was correlated with fibrosis and other studied variables using spearman correlation. A stepwise multiple regression analysis was also performed to examine independent factors associated with LSM. Different cut-off values of LSM were calculated for predicting individual fibrosis stages using receiver-operating characteristic curve. Cut-off values with optimal clinical performance (optimal sensitivity and specificity simultaneously) were selected.

RESULTS: The majority of HCV group had minimal activity (80%) and no/mild fibrosis (72%). On the other hand, the majority of AIH group had mild to moderate activity (70%) and moderate to severe fibrosis (95%) and all Wilson disease group had mild to moderate activity (100%) and moderate to severe fibrosis (100%). LSM correlated significantly with both FAF and Ishak scores and the correlation appeared better with the latter (r = 0.839 vs 0.879, P < 0.0001 for both). LSM discriminated individual stages of fibrosis with high performance. Sensitivity ranged from 81.4% to 100% and specificity ranged from 75.0% to 97.2%. When we compared LSM values for the same stage of fibrosis, they varied according to the different etiologies. Higher values were in AIH (16.15 ± 7.23 kPa) compared to Wilson disease (8.30 ± 0.84 kPa) and HCV groups (7.43 ± 1.73 kPa). Multiple regression analysis revealed that Ishak fibrosis stage was the only independent variable associated with higher LSM (P < 0.0001).

CONCLUSION: TE appears reliable in distinguishing different stages of liver fibrosis in children. However, its values vary according to the disease type. For that, a disease-specific estimation of cut-off values for fibrosis staging is worthy.

Keywords: Autoimmune hepatitis, Chronic hepatitis C, Liver fibrosis, Liver stiffness, Morphometry, Pediatrics, Transient elastography, Wilson disease

Core tip: Noninvasive prediction of liver fibrosis is a challenging issue especially in pediatric population. Liver stiffness, as assessed by transient elastography, was reported to be associated with liver fibrosis and therefore proposed as a candidate for fibrosis prediction. The accuracy of transient elastography has been shown to be excellent in a large number of adult studies, most of which are concerned with viral hepatitis. A few studies have also been performed in children. In addition to viral etiology, the current study is concerned with noninvasive assessment of fibrosis in other etiologies of pediatric chronic liver diseases. We compared the liver stiffness measurements with both the Ishak fibrosis score and the quantitative assessment of fibrosis using morphometry.