Hepatic Venous Pressure Gradient and Elastography in Porto-sinusoidal Vascular Disorder

January 30, 2023 updated by: Guilherme Rezende, Universidade Federal do Rio de Janeiro

Diagnostic Role of the Hepatic Venous Pressure Gradient and Elastography in Porto-sinusoidal Vascular Disorder With Portal Hypertension

Porto-sinusoidal vascular disorder (PSVD) is considered a rare cause of portal hypertension (PH), resulting from specific histological alterations that essentially affect the small portal branches and sinusoids, in the absence of cirrhosis.

In recent years, the recognition and importance of PSVD has increased, notably due to the widespread use of transient elastography (TE). However, the definitive diagnosis of PSVD can only be established through liver biopsy. Recent data show that PSVD should be suspected in patients with PH and TE ≤ 20 kPa and liver biopsy should be considered in this context.

The investigators hypothesize that hepatic venous pressure gradient (HVPG) and magnetic resonance liver elastography (MRE) may help in the selection of liver biopsy candidates for the diagnosis of PSVD.

The primary objective of the study is to describe HVPG and MRE values and liver biopsy findings in patients with PH and TE ≤ 20 kPa. The search for serum markers that can distinguish these patients from those with cirrhotic portal hypertension without the need for liver biopsy will also be the object of this study.

50 patients will be included, prospectively and retrospectively, in a comparative study between diagnostic methods, with a cross-sectional design.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Porto-sinusoidal vascular disorder (PSVD) is considered a rare cause of portal hypertension (PH), resulting from specific histological alterations that essentially affect the small portal branches and sinusoids, in the absence of cirrhosis.

In recent years, the recognition and importance of PSVD has increased, notably due to the widespread use of transient elastography (TE). However, the definitive diagnosis of PSVD can only be established through liver biopsy. Recent data show that PSVD should be suspected in patients with PH and TE ≤ 20 kPa and liver biopsy should be considered in this context.

The investigators hypothesize that hepatic venous pressure gradient (HVPG) and magnetic resonance liver elastography (MRE) may help in the selection of liver biopsy candidates for the diagnosis of PSVD.

Primary objectives are:

  • To describe the measurement of the hepatic venous pressure gradient (in mmHg) in patients with portal hypertension and transient hepatic elastography ≤ 20 kPa.
  • To describe hepatic (in kPa) and splenic (in kPa) stiffness measured by magnetic resonance elastography in patients with portal hypertension and transient hepatic elastography ≤ 20 kPa.
  • To describe the frequency of major histological findings for the diagnosis of portal sinusoidal vascular disorder (obliterative portal venopathy, regenerative nodular hyperplasia and incomplete septal cirrhosis) in patients with portal hypertension and transient hepatic elastography ≤ 20 kPa.

Secondary objectives are:

  • To describe the frequency of hepatic vein-to-vein communications in patients with portal hypertension and transient hepatic elastography ≤ 20 kPa.
  • To describe the frequency of minor histological findings for the diagnosis of portal sinusoidal vascular disease (portal tract abnormalities, architectural disturbances, nonzonal sinusoidal dilatation, mild perisinusoidal fibrosis) in patients with portal hypertension and transient hepatic elastography ≤ 20 kPa.
  • To compare the serum values of von Willebrand antigen factor (IU/mL) between patients diagnosed with porto-sinusoidal vascular disorder and those diagnosed with cirrhosis, after analysis of liver biopsy.
  • To compare the serum titers of procollagen III amino-terminal peptide (mcg/l) between patients diagnosed with portosinusoidal vascular disorder and those diagnosed with cirrhosis, after analysis of liver biopsy.

  • To compare the serum titers of anti-endothelial cell antibodies between patients diagnosed with portosinusoidal vascular disorder and those diagnosed with cirrhosis, after analysis of liver biopsy.

    50 patients will be included, prospectively and retrospectively, in a comparative study between diagnostic methods, with a cross-sectional design.

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Brazil
    • RJ
      • Rio de Janeiro, RJ, Brazil, 21941-617
        • Hospital Universitário Clementino Fraga Filho / Universidade Federal do Rio de Janeiro (UFRJ)
        • Contact:
        • Contact:
        • Principal Investigator:
          • Guilherme FM Rezende, MD, PhD
        • Sub-Investigator:
          • Eduardo Sica, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age ≥ 18 years;

  • Patients with specific signs of portal hypertension:

    1. Endoscopic: esophagogastric/ectopic varices;
    2. On imaging (US, CT or MRI): portosystemic collateral veins;
  • Transient hepatic elastography with valid values ≤ 20 kPa;
  • Signed written informed consent form.

Exclusion Criteria:

  • Contraindications to HVPG or percutaneous liver biopsy:

    1. Pregnancy
    2. Allergy to iodine
    3. Chronic kidney disease with creatinine clearance < 50 ml/min
    4. Anticoagulation
    5. RNI > 1.5
    6. Platelets < 50,000/mm3

  • Confounding factors:

    1. Hepatitis C treated with SVR

  • Conditions that exclude the diagnosis of PSVD:

    1. History of bone marrow transplant
    2. Budd-Chiari
    3. Congestive heart failure or Fontan surgery
    4. Abernethy's Syndrome
    5. Hereditary hemorrhagic telangiectasia
    6. Chronic cholestatic diseases
    7. Neoplastic hepatic infiltration
    8. Sarcoidosis
    9. Congenital hepatic fibrosis
    10. Hepatosplenic schistosomiasis
    11. Portal cavernoma / thrombosis with complete occlusion of the main portal vein.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: DIAGNOSTIC
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Portal hypertension patients with TE ≤ 20 kPa.
All patients included will undergo HVPG measurement and US-guided percutaneous liver biopsy. The exams will be performed in sequence, in the laboratory of hepatic hemodynamics. Within 4 to 8 weeks, a multiparametric magnetic resonance imaging of the abdomen with elastography will be performed, concluding the protocol.
Procedure: Hepatic vein pressure gradient measurement
HVPG will be performed after light conscious sedation and with noninvasive vital sign monitoring. The right jugular vein will be catheterized with ultrasound assistance and after local anesthesia. Then a venous introducer will be placed and a balloon-tipped catheter will be advanced under fluoroscopic control into the right hepatic vein. Free hepatic pressure will be obtained with the balloon deflated, keeping the catheter tip in the right hepatic vein. Then, wedged venous pressure will be measured by inflating the balloon with 2 ml of air. At this moment, complete occlusion of the catheterized hepatic vein can be confirmed by injecting iodinated contrast and observing its retention. The presence of veno-venous communications can be detected during the test. To calculate the gradient, we perform the simple difference between the two measurements. Measurements will be performed in triplicate and the average used as the final value.
Other Names:
  • HVPG
Procedure: Ultrasound-guided percutaneous liver biopsy
Percutaneous liver biopsy will be performed with the aid of US to choose the best site for the procedure, minimizing the incidence of complications. With the patient in dorsal decubitus, venous analgesia with fentanyl 25-50 mcg will be performed. After marking the appropriate site, skin asepsis and antisepsis will be performed with Chlorhexidine® and topical anesthesia with 1% lidocaine. Then, the liver will be punctured using a 14G semi-automatic tru-cut single-use liver biopsy needle. The recovered material will be stored in a 50 ml flask with 10% formaldehyde. Patients will remain at rest supervised for 4 hours, with hourly measurement of blood pressure (BP), heart rate (HR) and assessment of symptoms (abdominal pain, nausea, etc.). In the absence of any complications, patients will be discharged from the hospital.
Diagnostic test: Multiparametric Abdominal Magnetic Resonance with Elastography
The evaluation of the abdomen by MRI, with special interest to the liver and spleen, will be performed in a Siemens 3.0T Magnetom Prisma MR system. In addition to the routine protocol without contrast administration, MR elastography will be performed to assess liver stiffness and spleen stiffness. Data processing will be carried out at a Syngovia workstation.
Other Names:
  • MRE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hepatic venous pressure gradient measurement
Time Frame: 12 months
To describe the measurement of the hepatic venous pressure gradient (in mmHg) in patients with portal hypertension and transient hepatic elastography ≤ 20 kPa.
12 months
Magnetic resonance elastography
Time Frame: 12 months
To describe hepatic (in kPa) and splenic (in kPa) stiffness measured by magnetic resonance elastography in patients with portal hypertension and transient hepatic elastography ≤ 20 kPa.
12 months
Liver biopsy major findings
Time Frame: 12 months
To describe the frequency of major histological findings for the diagnosis of portal sinusoidal vascular disorder (obliterative portal venopathy, regenerative nodular hyperplasia and incomplete septal cirrhosis) in patients with portal hypertension and transient hepatic elastography ≤ 20 kPa.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hepatic vein-to-vein communications
Time Frame: 12 months
To describe the frequency of hepatic vein-to-vein communications in patients with portal hypertension and transient hepatic elastography ≤ 20 kPa.
12 months
Liver biopsy minor findings
Time Frame: 12 months
To describe the frequency of minor histological findings for the diagnosis of portal sinusoidal vascular disease (portal tract abnormalities, architectural disturbances, nonzonal sinusoidal dilatation, mild perisinusoidal fibrosis) in patients with portal hypertension and transient hepatic elastography ≤ 20 kPa.
12 months
Non-invasive markers - von Willebrand antigen factor
Time Frame: 12 months
To compare the serum values of von Willebrand antigen factor (IU/mL) between patients diagnosed with porto-sinusoidal vascular disorder and those diagnosed with cirrhosis, after analysis of liver biopsy.
12 months
Non-invasive markers - procollagen III amino-terminal peptide
Time Frame: 12 months
To compare the serum titers of procollagen III amino-terminal peptide (mcg/l) between patients diagnosed with portosinusoidal vascular disorder and those diagnosed with cirrhosis, after analysis of liver biopsy.
12 months
Non-invasive markers - anti-endothelial cell antibodies
Time Frame: 12 months
To compare the serum titers of anti-endothelial cell antibodies between patients diagnosed with portosinusoidal vascular disorder and those diagnosed with cirrhosis, after analysis of liver biopsy.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universidade Federal do Rio de Janeiro

Investigators

  • Principal Investigator: Guilherme FM Rezende, MD, PhD, Associate Professor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

March 1, 2023

Primary Completion (ANTICIPATED)

March 1, 2024

Study Completion (ANTICIPATED)

July 1, 2024

Study Registration Dates

First Submitted

January 12, 2023

First Submitted That Met QC Criteria

January 30, 2023

First Posted (ESTIMATE)

February 9, 2023

Study Record Updates

Last Update Posted (ESTIMATE)

February 9, 2023

Last Update Submitted That Met QC Criteria

January 30, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PSVD-1

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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