Clinical trial NCT04619966: Ultrasound Measurements of Hepatic Vasculatures and Hepatic Doppler Assessment of Healthy Children
Official title: Ultrasound Measurements of Hepatic Vasculatures and Hepatic Doppler Assessment of Healthy Children
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Portal Vein
Hepatic Veins
Hepatic Artery
Liver Circulation
Lead sponsor: Hong Kong Children's Hospital
Sponsor class: OTHER
First posted: 2020-11-06
Enrollment: 300
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients attending Hong Kong Children's Hospital for clinically indicated USG examination will be invited to participate in this study.

Brief summary: Flow dynamics in the liver is altered in different hepatobiliary and cardiac pathologies, causing changes in hepatic vasculatures sizes and flow pattern changes which can be assessed by ultrasound (USG) study. Before one can use these measurements and observations to diagnose pathologies, a clear grasp of normality is crucial.

In the field of pediatrics, this is particularly challenging as the normal range of measurements may change with age, weight, height, gender and race of children.

Taking hepatic veno-occlusive disease as an example, current literature is conflicting regarding whether sonographic findings show consistent association with the disease. Sonographic findings therefore now have limited role in contributing to the diagnosis.

This may be related to the lack of a robust age corrected normal range of measurement for reference.

Existing literature shows that the normal portal vein diameter varies with age, weight and height and possibly gender. Literature for normal measurements of hepatic vein and hepatic artery in children is lacking.

In this study, the investigators aim to conduct a prospective, cross-section observational study to establish the normal measurements ranges of hepatic vein, hepatic artery and portal vein in healthy children in the investigators' locality.

Flow patterns, including qualitative assessment and quantitative measurements of resistive index and flow velocities will also be assessed.

These age corrected normal measurements will be very helpful in the diagnosis and follow-up of hepatobiliary and cardiac pathologies associated with alterations in dynamics of hepatic circulation.

Detailed description: Trial Objectives and Purpose:

1. To establish normal limits of diameter of hepatic vein, hepatic artery and portal vein according to age, weight, height and gender.
2. To establish normal waveform pattern in ultrasound Doppler assessment of hepatic vein, hepatic artery and portal vein. (Qualitative analysis)
3. To establish normal limits of flow parameters assessed by ultrasound Doppler in hepatic vein, hepatic artery and portal vein according to age, weight, height and gender.

Trial Design:

A prospective cross-section observational study.

Recruitment of study subjects:

Patients attending Hong Kong Children's Hospital for clinically indicated USG examination will be invited to participate in this study under specific inclusion and exclusion criteria.

Treatment of subjects:

Recruited subjects will proceed to the clinically indicated USG study they are referred for first. After the clinically indicated USG study is completed, additional USG \& Doppler assessment of hepatic vasculatures will be performed, taking an additional 5 - 10 minutes.

All examinations will be done using a Philips EPIQ 5G ultrasound machine. Curvilinear or linear probe will be used depending on subjects' physique. Size measurements, qualitative and quantitative Doppler assessment of hepatic vein, hepatic artery and portal vein will be made and recorded.

Statistical method to be employed:

Continuous variables will be tested for normality by Shapiro-Wilk's test. Simple statistics including mean and standard deviations (+/- 2 SD) will be used to determine normal ranges for age.

Comparisons will be done by student's t-test. Relations between height, weight and gender with vessels diameter will be tested by Pearson correlation.

Linear multiple regression analysis will be utilized with vessels diameter as the dependent variable.

Number of subject to be enrolled (observation study): 300

Rationale:

Sample size = (Standard normal variate)2 X (Standard deviation)2 / Presicion2 Sample size = 1.962 X 22 / 12 Sample size = 15.37

Standard normal variate = 1.96 at 5% Type I error Standard deviation = up to 2mm (from prior study of portal vein diameter) Precision = 1mm

In view of aim of determining age corrected normal range of vessels diameter in children, a much bigger sample size will be obtained to improve accuracy.

Target to include 300 children in this study.

Age groups:

Around 30 cases for each of the following age groups:

1. 0 - 1 years old
2. 1 - 2 years old
3. 2 - 4 years old
4. 4 - 6 years old
5. 6 - 8 years old
6. 8 - 10 years old
7. 10 - 12 years old
8. 12 - 14 years old
9. 14 - 16 years old
10. 16- 18 years old

Eligibility criteria: Inclusion Criteria:

1. Patient \< / = 18 years of age.
2. No history of hepatobiliary nor cardiac pathology as checked with record in ePR. Verbal confirmation will be done with patient or parent / legal guardian.
3. Attending USG study other than that of the hepatobiliary system. (ie. Patients attending for thyroid USG, urinary system USG, musculoskeletal system USG etc.)

Exclusion Criteria:

1. Patient \> 18 years of age
2. Known history of hepatobiliary or cardiac pathology.
3. Unstable patients.
4. Intolerance of USG examination
5. Uncooperative patients.
6. Patient requiring sedation for USG study.

Primary outcomes:
measure: Hepatic veins diameter (in mm) measured by grey scale ultrasound at 1 - 2 cm from confluence with inferior vena cava
timeFrame: Baseline
measure: Hepatic veins Doppler assessment of flow direction (towards or away from inferior vena cava)
timeFrame: Baseline
measure: Hepatic veins Doppler assessment of flow pulsatility (yes or no)
timeFrame: Baseline
measure: Hepatic veins Doppler assessment of flow phasicity (monophasic, biphasic or triphasic)
timeFrame: Baseline
measure: Hepatic veins Quantitative Doppler measurement of maximum flow rate (cm/s)
timeFrame: Baseline
measure: Hepatic veins Quantitative Doppler measurement of minimum flow rate (cm/s)
timeFrame: Baseline
measure: Hepatic veins Quantitative Doppler measurement of pulsatility index (only if pulsatility is present)
timeFrame: Baseline
measure: Hepatic artery diameter (in mm) measured by grey scale ultrasound at liver hilum
timeFrame: Baseline
measure: Hepatic artery Doppler assessment of flow direction (hepatofugal or hepatopetal)
timeFrame: Baseline
measure: Hepatic artery Doppler assessment of flow pulsatility (yes or no)
timeFrame: Baseline
measure: Hepatic artery Doppler assessment of flow phasicity (monophasic, biphasic or triphasic)
timeFrame: Baseline
measure: Hepatic artery quantitative Doppler measurement of peak systolic velocity (cm/s)
timeFrame: Baseline
measure: Hepatic artery quantitative Doppler measurement of end diastolic velocity (cm/s)
timeFrame: Baseline
measure: Hepatic artery quantitative Doppler measurement of pulsatility index
timeFrame: Baseline
measure: Hepatic artery quantitative Doppler measurement of resistive index
timeFrame: Baseline
measure: Hepatic artery quantitative Doppler measurement of flow volume (ml/s) (measured if feasible)
timeFrame: Baseline
measure: Portal vein diameter (in mm) measured by grey scale ultrasound at liver hilum
timeFrame: Baseline
measure: Portal vein Doppler assessment of flow direction (hepatopetal or hepatofugal)
timeFrame: Baseline
measure: Portal vein Doppler assessment of flow pulsatility (yes or no)
timeFrame: Baseline
measure: Portal vein Doppler assessment of flow phasicity (monophasic, biphasic or triphasic)
timeFrame: Baseline
measure: Portal vein quantitative Doppler measurement of maximum flow rate (cm/s)
timeFrame: Baseline
measure: Portal vein quantitative Doppler measurement of minimum flow rate (cm/s)
timeFrame: Baseline
measure: Portal vein quantitative Doppler measurement of pulsatility index (only if pulsatility is present)
timeFrame: Baseline
measure: Portal vein quantitative Doppler measurement of flow volume (ml/s)
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Hong Kong Children's Hospital
Study officials:
affiliation: Hong Kong Children's Hospital
name: Pui Kwan Joyce Chan, MBChB
role: PRINCIPAL_INVESTIGATOR
References:
citation: Patriquin HB, Perreault G, Grignon A, Boisvert J, Filiatrault D, Garel L, Blanchard H. Normal portal venous diameter in children. Pediatr Radiol. 1990;20(6):451-3. doi: 10.1007/BF02075206.
citation: Soyupak S, Gunesli A, Seydaoglu G, Binokay F, Celiktas M, Inal M. Portal venous diameter in children: normal limits according to age, weight and height. Eur J Radiol. 2010 Aug;75(2):245-7. doi: 10.1016/j.ejrad.2009.03.052. Epub 2009 May 5.
citation: Weinreb J, Kumari S, Phillips G, Pochaczevsky R. Portal vein measurements by real-time sonography. AJR Am J Roentgenol. 1982 Sep;139(3):497-9. doi: 10.2214/ajr.139.3.497. No abstract available.
citation: Jequier S, Jequier JC, Hanquinet S, Gong J, Le Coultre C, Belli DC. Doppler waveform of hepatic veins in healthy children. AJR Am J Roentgenol. 2000 Jul;175(1):85-90. doi: 10.2214/ajr.175.1.1750085.
citation: Herbetko J, Grigg AP, Buckley AR, Phillips GL. Venoocclusive liver disease after bone marrow transplantation: findings at duplex sonography. AJR Am J Roentgenol. 1992 May;158(5):1001-5. doi: 10.2214/ajr.158.5.1566656.
citation: McCarville MB, Hoffer FA, Howard SC, Goloubeva O, Kauffman WM. Hepatic veno-occlusive disease in children undergoing bone-marrow transplantation: usefulness of sonographic findings. Pediatr Radiol. 2001 Feb;31(2):102-5. doi: 10.1007/s002470000373.
citation: Hommeyer SC, Teefey SA, Jacobson AF, Higano CS, Bianco JA, Colacurcio CJ, McDonald GB. Venocclusive disease of the liver: prospective study of US evaluation. Radiology. 1992 Sep;184(3):683-6. doi: 10.1148/radiology.184.3.1509050.
citation: Corbacioglu S, Carreras E, Ansari M, Balduzzi A, Cesaro S, Dalle JH, Dignan F, Gibson B, Guengoer T, Gruhn B, Lankester A, Locatelli F, Pagliuca A, Peters C, Richardson PG, Schulz AS, Sedlacek P, Stein J, Sykora KW, Toporski J, Trigoso E, Vetteranta K, Wachowiak J, Wallhult E, Wynn R, Yaniv I, Yesilipek A, Mohty M, Bader P. Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in pediatric patients: a new classification from the European society for blood and marrow transplantation. Bone Marrow Transplant. 2018 Feb;53(2):138-145. doi: 10.1038/bmt.2017.161. Epub 2017 Jul 31.