Clinical trial NCT04380493: The Use of the Transient Elastography Paediatric Probe, Compared to the M Probe, Indirect Biomarkers and Histology
Official title: Special Considerations for the Use of the Transient Elastography Paediatric Probe, Compared to the Standard M Probe, Indirect Serological Markers and Histology
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Elastography
Fibrosis, Liver
Pediatrics
Chronic Liver Disease
Keywords: Elastography
liver biopsy
biopsy
indirect biomarkers
Lead sponsor: Hospital Vall d'Hebron
Sponsor class: OTHER
First posted: 2020-05-08
Enrollment: 141
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pediatric patients of both sexes, aged 0 months to 18 years, suffering from various chronic liver diseases.

Brief summary: 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

Detailed description: 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.).

Eligibility criteria: 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.

Primary outcomes:
measure: Validation of FibroScan's® pediatric (S) probe in children
timeFrame: 4 years
Secondary outcomes:
measure: Validation of indirect fibrosis markers
timeFrame: 4 years
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
Study officials:
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