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

Not Applicable

Not yet recruiting

• Conditions: Non-Cirrhotic Portal Fibrosis; Incomplete Septal Cirrhosis; Idiopathic Non-Cirrhotic Portal Hypertension; Portal Hypertension; Idiopathic Portal Hypertension; Non-Cirrhotic Portal Hypertension; Obliterative Portal Venopathy; Hepatoportal Sclerosis; Regenerative Nodular Hyperplasia; Vascular Disorder of Liver
• Interventions: Procedure: Hepatic vein pressure gradient measurement; Procedure: Ultrasound-guided percutaneous liver biopsy; Diagnostic Test: Multiparametric Abdominal Magnetic Resonance with Elastography

• Registration Number: NCT05719857
• Lead Sponsor: Universidade Federal do Rio de Janeiro

Brief Summary

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.

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 Timeline

• Status Verified: 2023-01
• Study First Submitted: 2023-01-12
• Study First Submitted QC: 2023-01-30
• Last Update Submitted: 2023-01-30
• Study First Posted: 2023-02-09
• Last Update Posted: 2023-02-09
• Study Start: 2023-03
• Primary Completion: 2024-03
• Study Completion: 2024-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 50

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Portal hypertension patients with TE ≤ 20 kPa.	Hepatic vein pressure gradient measurement	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.
Portal hypertension patients with TE ≤ 20 kPa.	Ultrasound-guided percutaneous liver biopsy	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.
Portal hypertension patients with TE ≤ 20 kPa.	Multiparametric Abdominal Magnetic Resonance with Elastography	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.

Primary Outcome Measures

Name	Time	Method
Liver biopsy major findings	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.
Hepatic venous pressure gradient measurement	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.
Magnetic resonance elastography	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.

Secondary Outcome Measures

Name	Time	Method
Non-invasive markers - procollagen III amino-terminal peptide	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.
Hepatic vein-to-vein communications	12 months	To describe the frequency of hepatic vein-to-vein communications in patients with portal hypertension and transient hepatic elastography ≤ 20 kPa.
Liver biopsy minor findings	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.
Non-invasive markers - von Willebrand antigen factor	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.
Non-invasive markers - anti-endothelial cell antibodies	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.

Trial Locations

Locations (1)

Hospital Universitário Clementino Fraga Filho / Universidade Federal do Rio de Janeiro (UFRJ); 🇧🇷 Rio de Janeiro, RJ, Brazil