Nonfasted Liver Stiffness Correlates with Liver Disease Parameters and Portal Hypertension in Pediatric Cholestatic Liver Disease

Abstract

Elastographic measurement of liver stiffness is of growing importance in the assessment of liver disease. Pediatric experiences with this technique are primarily single center and limited in scope. The Childhood Liver Disease Research Network provided a unique opportunity to assess elastography in a well-characterized multi-institutional cohort. Children with biliary atresia (BA), alpha-1 antitrypsin deficiency (A1ATD), or Alagille syndrome (ALGS) followed in a prospective longitudinal network study were eligible for enrollment in a prospective investigation of transient elastography (FibroScan). Studies were performed in participants who were nonfasted and nonsedated. Liver stiffness measurements (LSMs) were correlated with standard clinical and biochemical parameters of liver disease along with a research definition of clinically evident portal hypertension (CEPH) graded as absent, possible, or definite. Between November 2016 and August 2019, 550 participants with a mean age of 8.8 years were enrolled, 458 of whom had valid LSMs (BA, n = 254; A1ATD, n = 104; ALGS, n = 100). Invalid scans were more common in participants <2 years old. There was a positive correlation between LSM and total bilirubin, international normalized ratio (INR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), GGT to platelet ratio (GPR), pediatric end-stage liver disease score, AST to platelet ratio index, and spleen size, and a negative correlation with albumin and platelet count in BA, with similar correlations for A1ATD (except AST, ALT, and albumin) and ALGS (except for INR, GGT, GPR, and ALT). Possible or definite CEPH was more common in BA compared to ALGS and A1ATD. LSM was greater in definite versus absent CEPH in all three diseases. Disease-specific clinical and biochemical characteristics of the different CEPH grades were observed. Conclusion: It is feasible to obtain LSMs in children, especially over the age of 2 years. LSM correlates with liver parameters and portal hypertension, although disease-specific patterns exist.

Fig. 1

Sample selection.

Fig. 2

Selected scatter plots of laboratory parameters and LSMs. (A‐F) LSMs (in kPA) are shown relative to various liver parameters in (A‐E) BA and (F) ALGS. (B) LSM, APRI, and (E,F) GGTare log transformed, while (A,C,D) platelet count, PELD score, and albumin are not.

Fig. 3

LSM by disease type and CEPH status. Box and whisker plots of LSM from valid scans in participants with BA, A1ATD, and ALGS. CEPH status of absent, possible, or definite is indicated for each of the diseases. The number below the box and whisker plot indicates the number of participants with that disease and CEPH status. The line in the middle of the box is the median, the diamond is the mean, the bottom and top of the box are the twenty‐fifth and seventy‐fifth percentiles, respectively. The whiskers go to the most extreme values that are with 1.5× the IQR, with individual outliers beyond this indicated by open circles. P values for specific comparisons are shown.

Fig. 4

Radar plots of clinical parameters according to disease and CEPH status. Median values of the parameters for each group are plotted along the spokes of the circles. Values are scaled so that the center of each radar plot represents more favorable values for the clinical parameters and the vertices represent the most unfavorable median value observed among all the groups. Abbreviations: Bili, total bilirubin; Plt, platelet count; Spln, spleen.