The Use of the Transient Elastography Paediatric Probe, Compared to the M Probe, Indirect Biomarkers and Histology
The Use of the Transient Elastography Paediatric Probe, Compared to the M Probe, Indirect Biomarkers and Histology
The purpose of this study is to assess the reliability, reproducibility and accuracy of the
 paediatric probe of transient elastography in detecting liver fibrosis in children, besides
 its limitations and side effects. At the same time, to assess whether indirect fibrosis
 markers are a valid tool to detect absence or mild fibrosis in paediatric patients
A retrospective cohort study, including all patients younger than 18 years of age with
 chronic liver disease who underwent a transient elastography, was performed. The study was
 carried out in the joint Unit of Paediatric Complex Hepatology and Liver Transplant,
 encompassing two third level paediatric hospitals, between 2015 and 2019. The study protocol
 was approved by local ethic committee (identifier code: PR(AMI)147/2019) and informed consent
 was signed by patient's legal guardians and patients over 16 years old.

 Liver stiffness was assessed with FibroScan® (Echosens, France, model 502, class IIa, year
 2010), which was performed by an experienced operator to avoid interobserver bias and in the
 same standardized conditions (fasting, decubitus position, right arm in maximal abduction,
 transducer placed over the right lobe). S probe (model 8; 5 MHz; diameter 5 mm), that
 measures depths ranging from 15-50 mm (S1: 15-40 mm; S2: 20-50 mm), was selected if chest
 circumference (CC) < 75 cm (S1: ≤ 45 cm; S2: 45-75 cm). M probe (3.5 MHz; diameter 7 mm),
 measuring depths range 35-75mm, was used if CC ≥ 75 cm. Both probes met the calibration
 terms. Elastographic parameters studied were: stiffness (KPa), interquartile range (IQR) and
 success rate (SR). Adult-validated liver stiffness measurement ranges to classify the
 fibrosis degree were taken as a reference: F0-F1 (≤7.6 KPa), F2 (7.7-9.4 KPa), F3 (9.5-14
 KPa) and F4 (>14 KPa). The examination was successful when the median of at least 10 valid
 values, had a SR higher than 60% and with an IQR/LSM lower than 30%.

 The following sociodemographic, clinical and analytical data were collected: age, sex,
 underlying liver disease and analytical parameters (alanine aminotransferase (ALT) U/L,
 aspartate aminotransferase (AST) U/L, gamma glutamyl transferase (GGT) U/L, total bilirubin
 (mg/dl), cholesterol (mg/dl), platelets (109/L), prothrombin time (%)). The following liver
 fibrosis test Scores were calculated using the obtained data:

 -  Fibrosis 4 Score (FIB-4) = Age (years) x AST (U/L) / platelets (109/L) x √ALT (U/L).

 -  AST to Platelet Radio Index (APRI) = AST (upper normal limit) (UI/l)/ platelets x 109 x
 100.

 Eighteen clinically indicated liver biopsies were performed and staged according METAVIR
 score (F0-F4). Blood test, fibrosis scores and biopsies were performed within 6 months of
 transient elastography. No clinical or analytical changes were observed during this period.

 The Faces Pain Scale was used for assessing pain severity. Statistical analysis:
 Kolmogorov-Smirnov test checked out if variables followed a normal distribution. Continuous
 variables are presented as mean ± standard deviation or median (interquartile range) and
 categorical variables as number of subjects and percentage. Correlation between continuous
 variables were calculated using Pearson's and Spearman's correlation coefficient. The
 variance's analysis (ANOVA) and the Kruskal Wallis test were used to compare qualitative with
 quantitative variables. Two-tailed p-Values of <0.05 were considered as statistically
 significant. Sensitivity, specificity, positive predictive value and negative predictive
 value were calculated in the assessment of FIB-4 and APRI as a diagnostic test to detect
 absence or mild fibrosis (F0-F1), using the results obtained by TE as a reference. The
 statistical analyses were performed with SPSS software (v. 21, SPSS Inc., Chicago, IL, USA)
 and Prism (v. 7.04 GraphPad Software Inc.).
Inclusion Criteria:

 -  Patients younger than 18 years of age with chronic liver disease who underwent a
 transient elastography.

 -  Parents / legal guardians and the patients themselves, if applicable, have read,
 understood and signed the informed consent of the study.

 Exclusion Criteria:

 -  Patients who do not meet all the inclusion criteria for inclusion in the study
 protocol.