Endoscopic Ultrasound Shear Wave for Liver Fibrosis in MASLD Patients: The RUMIPAMBA Trial

Estimation of Liver Fibrosis in Patients With MASLD Screening Criteria Through Endoscopic Ultrasound-guided Shear Wave vs Transabdominal Ultrasound and Transient Elastography: The RUMIPAMBA Diagnostic Trial

Currently, there is no description of the contribution of the endoscopic ultrasound (EUS)-guided shear wave elastography (SWE) when describing liver fibrosis in patients with screening criteria of metabolic dysfunction-associated steatotic liver disease (MASLD), with absent-to-mild liver fibrosis. Similar research has been published but using vibration-controlled transient elastography (VCTE), recommended mainly due to its lower cost and less invasiveness. However, VCTE is limited to the anatomical proportions of the patient's body, and cannot assess the right hepatic lobe with less reliability, contrary to the EUS-SWE.

Study Overview

• Status: Recruiting
• Conditions: Fibrosis, Liver; Liver Steatosis
• Intervention / Treatment: Device: Transparietal ultrasound (US)-based shear wave elastography (SWE) attenuation measurement; Device: Transparietal ultrasound (US)-based shear wave elastography (SWE) stiffness measurement; Device: Vibration-controlled transient elastography (VCTE) attenuation measurement; Device: Vibration-controlled transient elastography (VCTE) stiffness measurement; Device: Endoscopic ultrasound (EUS)-guided shear wave elastography (SWE) stiffness measurement

Detailed Description

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly non-alcoholic fatty liver disease (NAFLD), is an umbrella term which involves simple liver steatosis, metabolic-associated steatohepatitis (MASH) and MASH-related liver cirrhosis. Liver steatosis relies on imaging or biomarkers, but liver biopsy remains the gold standard for its diagnosis and grading. It comprehends intracellular accumulation of triacylglycerol (TAG) as microvascular or macrovascular lipid droplets in at least 5% of hepatocytes. Liver biopsy is invasive, requires a high-quality biopsy sample, can mislead a diagnosis due to sampling bias, depends on pathologist interpretation variability and implies adverse events related to the punction.

There are non-invasive resources useful for the screening and surveillance of liver steatosis and fibrosis. Apart from serum biomarkers, non-invasive technologies designed for this purpose use transabdominal ultrasound (US)-based elastography, namely: US strain, acoustic radiation force impulse (ARFI), point shear wave elastography (pSWE), two-dimension shear wave elastography (2D-SWE) and vibration-controlled transient elastography (VCTE). Although VCTE presents anatomical limitations when used in overweight patients or assessing the right hepatic lobe, it is largely accepted by international guidelines for assessing liver steatosis and fibrosis. Endoscopic ultrasound (EUS)-guided shear wave elastography (SWE) is independent of the anatomical proportions of the patients, and it permits a more reliable right hepatic lobe evaluation. However, it is an invasive and high-cost procedure.

VCTE, US-ARFI and EUS-SWE determine liver fibrosis quantitatively in terms of liver stiffness through kiloPascals. There are four important gaps in the literature: First, the diagnostic accuracy of VCTE for liver steatosis has been profoundly analysed in NAFLD, but in a wide spectrum of liver fibrosis patients, from absent to cirrhosis. These limits finding extrapolations for screening and surveillance. Second, comparisons between VCTE, US-ARFI and EUS-SWE have concentrated on liver fibrosis or cirrhosis, but they have not been compared head-to-head in the context of absent-to-mild liver fibrosis vs controls. Third, there is no determined diagnostic accuracy for EUS-SWE for an early liver fibrosis estimation in MASLD patients. It is useful considering EUS is becoming a more popular procedure. Finally, and to be consequent with the third point, the identification and grading of liver steatosis and fibrosis still need to be described in the nowadays called MASLD patients.

The present study aims to determine the difference in the estimation of liver fibrosis among VCTE, US-ARFI and EUS-SWE in patients with clinical criteria of MASLD screening but absent-to-mild liver fibrosis, according to non-invasive methods.

This study has been called by the authors through the acronym RUMIPAMBA, which means "Role of endoscopic Ultrasound-guided shear wave for MASLD-related liver steatosis and fibrosis Identification in Patients with Absent to Mild Basal fibrosis, based on non-invasive Analytical laboratory tests". In the general culture, Rumipamba is the name of an archaeological prehispanic and preincaic park from Quito, the capital city of Ecuador.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Miguel Puga-Tejada, MD; Phone Number: +353 87 686 0537; Email: mpuga@ieced.ec
• Study Contact Backup: Name: Jorge Baquerizo-Burgos, MD; Phone Number: +593 98 962 7111; Email: jorgebaquerizoburgos@gmail.com

Study Locations

• Ecuador
  • Guayas
    • Guayaquil, Guayas, Ecuador, 090505
      • Recruiting
      • Instituto Ecuatoriano de Enfermedades Digestivas (IECED) Gastroclinica SA
      • Principal Investigator: Carlos Robles-Medranda, MD FASGE
      • Sub-Investigator: Raquel Del Valle, MD
      • Contact: Jorge Baquerizo-Burgos, MD; Phone Number: +593 98 962 7111; Email: jorgebaquerizoburgos@gmail.com
      • Contact: Miguel Puga-Tejada, MD MSc; Phone Number: +353 87 686 0537; Email: mpuga@ieced.ec

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients referred for any kind of endoscopic procedure.
• Without clinical suspicion of advanced liver fibrosis.
• Acceptance to participate in the study.

Exclusion Criteria:

• History of greater amounts of alcohol per week (140 g/week and 210 g/week for females and males respectively).
• Significant or advanced fibrosis by Fibrosis-4 Index (FIB4) or the aspartate aminotransferase to platelet ratio index (APRI).
• Any liver space-occupying lesion in the US.
• Comorbidities or conditions related to avoidance of interventional procedures, namely: pregnancy or nursing, coagulopathy or any risk of bleeding, Anaesthesiology Society Association classification IV or higher, New York Heart Association functional class III or IV.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MASLD screening patients; Patients with requirements of screening following the European Association for the Study of the Liver (EASL) 2016 recommendations. The MASLD screening group will be compounded by patients with at least one of the following criteria: Over fifty years old;; Body mass index (BMI) over 25 kg/m2;; Diabetes mellitus type 2;; Metabolic syndrome; or; Persistently elevated liver enzymes.	Device: Transparietal ultrasound (US)-based shear wave elastography (SWE) attenuation measurement; The operator will be blinded to any clinical record. Before US-SWE, the patient must be fasted for a minimum of 4 hours and must remain alcohol-free for 7 days. Using an Aloka Arietta 850 (Olympus America, PA, USA), each patient must be supine. Upon breath-hold at the end of expiration, ten measurements will be obtained with the probe placed in the area of the right hepatic lobe through an intercostal space.; Other Names: US-SWE attenuation; Device: Transparietal ultrasound (US)-based shear wave elastography (SWE) stiffness measurement; The operator will be blinded to any clinical record. Before US-SWE, the patient must be fasted for a minimum of 4 hours and must remain alcohol-free for 7 days. Using an Aloka Arietta 850 (Olympus America, PA, USA), each patient must be supine. Upon breath-hold at the end of expiration, ten measurements will be obtained with the probe placed in the area of the right hepatic lobe through an intercostal space.; Other Names: US-SWE stiffness; Device: Vibration-controlled transient elastography (VCTE) attenuation measurement; The operator will be blinded to any clinical record. Before VCTE, the patient must be fasted for a minimum of 4 hours and must remain alcohol-free for 7 days. Using the FibroScan® Compact 530 (Echosens, Paris, France), each patient must be supine with the right arm in abduction and the ipsilateral hand resting under the head. Upon breath-hold at the end of expiration, ten measurements will be obtained with the M-probe placed in the area of the right hepatic lobe through an intercostal space. Transition to an extra large probe will be based on a VCTE automatic probe selection tool prompt.; Other Names: VCTE attenuation; Device: Vibration-controlled transient elastography (VCTE) stiffness measurement; The operator will be blinded to any clinical record. Before VCTE, the patient must be fasted for a minimum of 4 hours and must remain alcohol-free for 7 days. Using the FibroScan® Compact 530 (Echosens, Paris, France), each patient must be supine with the right arm in abduction and the ipsilateral hand resting under the head. Upon breath-hold at the end of expiration, ten measurements will be obtained with the M-probe placed in the area of the right hepatic lobe through an intercostal space. Transition to an extra large probe will be based on a VCTE automatic probe selection tool prompt.; Other Names: VCTE measurement; Device: Endoscopic ultrasound (EUS)-guided shear wave elastography (SWE) stiffness measurement; EUS-SWE will be performed by an experienced endoscopist, blinded to clinical records. The expert will use the ArrietaTM 850 EUS console (Fujifilm, Tokyo, Japan) using a linear ultrasound video gastroscope EUS-J10 (Pentax Medical, Hoya Corp, Japan). Both lobes will be evaluated. The transducer will be positioned in the gastric window to visualize right liver segment number five and left liver segment two or three. The elastogram region of interest (ROI) will be placed within the liver tissue at a distance ≥10 mm beneath the hepatic capsule in an area free of vessels and artefacts. A 10-mm circular ROI will be placed within the elastogram at a depth of 4-5 cm from the skin, and a minimum of ten successful kilopascal measurements will be obtained. In the first stage of this research, the EUS-SWE measurement will be limited to the estimation of liver fibrosis only. Currently, available EUS-SWE equipment does not allow the estimation of the attenuation.; Other Names: EUS-SWE attenuation
Other: Controls; Patients without requirements of screening following the European Association for the Study of the Liver (EASL) 2016 recommendations. The control group will be compounded by patients who will not present any of the following criteria: Over fifty years old;; Body mass index (BMI) over 25 kg/m2;; Diabetes mellitus type 2;; Metabolic syndrome; and; Persistently elevated liver enzymes. To be a control participant does not mean that the patient is a healthy participant. The control participants are patients who request any type of endoscopy and fulfil the criteria not to screen for liver steatosis. For example, a 48-year-old male with 21 kg/m2 BMI, without diabetes mellitus type 2, any metabolic syndrome-related comorbidities, with normal liver enzymes and who refused an episode of persistently elevated liver enzymes, with persistent reflux disease after two months of proton pump inhibitor therapy,	Device: Transparietal ultrasound (US)-based shear wave elastography (SWE) attenuation measurement; The operator will be blinded to any clinical record. Before US-SWE, the patient must be fasted for a minimum of 4 hours and must remain alcohol-free for 7 days. Using an Aloka Arietta 850 (Olympus America, PA, USA), each patient must be supine. Upon breath-hold at the end of expiration, ten measurements will be obtained with the probe placed in the area of the right hepatic lobe through an intercostal space.; Other Names: US-SWE attenuation; Device: Transparietal ultrasound (US)-based shear wave elastography (SWE) stiffness measurement; The operator will be blinded to any clinical record. Before US-SWE, the patient must be fasted for a minimum of 4 hours and must remain alcohol-free for 7 days. Using an Aloka Arietta 850 (Olympus America, PA, USA), each patient must be supine. Upon breath-hold at the end of expiration, ten measurements will be obtained with the probe placed in the area of the right hepatic lobe through an intercostal space.; Other Names: US-SWE stiffness; Device: Vibration-controlled transient elastography (VCTE) attenuation measurement; The operator will be blinded to any clinical record. Before VCTE, the patient must be fasted for a minimum of 4 hours and must remain alcohol-free for 7 days. Using the FibroScan® Compact 530 (Echosens, Paris, France), each patient must be supine with the right arm in abduction and the ipsilateral hand resting under the head. Upon breath-hold at the end of expiration, ten measurements will be obtained with the M-probe placed in the area of the right hepatic lobe through an intercostal space. Transition to an extra large probe will be based on a VCTE automatic probe selection tool prompt.; Other Names: VCTE attenuation; Device: Vibration-controlled transient elastography (VCTE) stiffness measurement; The operator will be blinded to any clinical record. Before VCTE, the patient must be fasted for a minimum of 4 hours and must remain alcohol-free for 7 days. Using the FibroScan® Compact 530 (Echosens, Paris, France), each patient must be supine with the right arm in abduction and the ipsilateral hand resting under the head. Upon breath-hold at the end of expiration, ten measurements will be obtained with the M-probe placed in the area of the right hepatic lobe through an intercostal space. Transition to an extra large probe will be based on a VCTE automatic probe selection tool prompt.; Other Names: VCTE measurement; Device: Endoscopic ultrasound (EUS)-guided shear wave elastography (SWE) stiffness measurement; EUS-SWE will be performed by an experienced endoscopist, blinded to clinical records. The expert will use the ArrietaTM 850 EUS console (Fujifilm, Tokyo, Japan) using a linear ultrasound video gastroscope EUS-J10 (Pentax Medical, Hoya Corp, Japan). Both lobes will be evaluated. The transducer will be positioned in the gastric window to visualize right liver segment number five and left liver segment two or three. The elastogram region of interest (ROI) will be placed within the liver tissue at a distance ≥10 mm beneath the hepatic capsule in an area free of vessels and artefacts. A 10-mm circular ROI will be placed within the elastogram at a depth of 4-5 cm from the skin, and a minimum of ten successful kilopascal measurements will be obtained. In the first stage of this research, the EUS-SWE measurement will be limited to the estimation of liver fibrosis only. Currently, available EUS-SWE equipment does not allow the estimation of the attenuation.; Other Names: EUS-SWE attenuation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endoscopic ultrasound (EUS)-guided liver biopsy steatosis grade	The EUS-guided liver biopsy findings, per hepatic lobe, will be standardised through the steatosis-Activity-Fibrosis (SAF) score. The SAF scores steatosis (0-3), ballooning degeneration (0-2), lobular inflammation (0-2), and fibrosis (0-4). Liver steatosis is present when proper steatosis is present, and when both features of activity (ballooning and lobular inflammation) display at least grade 1.	Six months
Vibration-controlled transient elastography (VCTE) liver steatosis grade	Liver steatosis will be defined by elastography using the controlled attenuation parameter (CAP), measured in decibels per meter.	Six months
Transparietal ultrasound (US)-based shear wave elastography (SWE) liver steatosis grade	Liver steatosis will be defined by elastography using the attenuation coefficient (ATT), measured in decibels per meter. The ATT corresponds to the VCTE CAP measurement.	Six months
Endoscopic ultrasound (EUS)-guided shear wave elastography (SWE) liver steatosis grade	Liver steatosis per hepatic lobe will be defined by elastography using the attenuation coefficient (ATT) measurement. The ATT corresponds to the VCTE CAP measurement.	Six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endoscopic ultrasound (EUS)-guided liver biopsy fibrosis grade	The EUS-guided liver biopsy findings, per hepatic lobe, will be standardised through the Brunt system.	Six months
Vibration-controlled transient elastography (VCTE) liver fibrosis grade	Liver steatosis will be defined by elastography using kilopascals.	Six months
Transparietal ultrasound (US)-based shear wave elastography (SWE) liver fibrosis grade	Liver steatosis will be defined by elastography using kilopascals.	Six months
Endoscopic ultrasound (EUS)-guided shear wave elastography (SWE) liver fibrosis grade	Liver steatosis per hepatic lobe will be defined by elastography using kilopascals.	Six months

Collaborators and Investigators

• Sponsor: Instituto Ecuatoriano de Enfermedades Digestivas
• Investigators: Principal Investigator: Carlos Robles-Medranda, MD, Instituto Ecuatoriano de Enfermedades Digestivas (IECED)

Publications and helpful links

General Publications

• Yazdani L, Rafati I, Gesnik M, Nicolet F, Chayer B, Gilbert G, Volniansky A, Olivie D, Giard JM, Sebastiani G, Nguyen BN, Tang A, Cloutier G. Ultrasound Shear Wave Attenuation Imaging for Grading Liver Steatosis in Volunteers and Patients With Non-alcoholic Fatty Liver Disease: A Pilot Study. Ultrasound Med Biol. 2023 Oct;49(10):2264-2272. doi: 10.1016/j.ultrasmedbio.2023.06.020. Epub 2023 Jul 21.
• Liu GT, Ni QF, Zhang YH, Dong XM, Zhou C, Shen B, Zhu JY, Chen YJ, Zhu Z. Application of noninvasive test (acoustic attenuation imaging and ultrasonic shear wave elastography) to grade nonalcoholic fatty liver disease: An observational study. Medicine (Baltimore). 2023 Aug 11;102(32):e34550. doi: 10.1097/MD.0000000000034550.
• De A, Duseja A. Natural History of Simple Steatosis or Nonalcoholic Fatty Liver. J Clin Exp Hepatol. 2020 May-Jun;10(3):255-262. doi: 10.1016/j.jceh.2019.09.005. Epub 2019 Sep 20.
• Pandyarajan V, Gish RG, Alkhouri N, Noureddin M. Screening for Nonalcoholic Fatty Liver Disease in the Primary Care Clinic. Gastroenterol Hepatol (N Y). 2019 Jul;15(7):357-365.
• Kohli DR, Mettman D, Andraws N, Haer E, Porter J, Ulusurac O, Ullery S, Desai M, Siddiqui MS, Sharma P. Comparative accuracy of endosonographic shear wave elastography and transcutaneous liver stiffness measurement: a pilot study. Gastrointest Endosc. 2023 Jan;97(1):35-41.e1. doi: 10.1016/j.gie.2022.08.035. Epub 2022 Aug 29.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: October 2, 2023
• First Submitted That Met QC Criteria: October 21, 2023
• First Posted (Actual): October 26, 2023

Study Record Updates

• Last Update Posted (Actual): September 24, 2024
• Last Update Submitted That Met QC Criteria: September 22, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Elastography; Liver fibrosis; Liver steatosis; Fatty liver; Endosonography
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Fatty Liver; Liver Cirrhosis
• Other Study ID Numbers: IECED-02102023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No