Hepatoportal Sclerosis, Idiopathic Non-Cirrhotic Portal Hypertension, Idiopathic Portal Hypertension, Incomplete Septal Cirrhosis, Non-Cirrhotic Portal Fibrosis, Non-Cirrhotic Portal Hypertension, Obliterative Portal Venopathy, Portal Hypertension, Regenerative Nodular Hyperplasia, Vascular Disorder of Liver
Conditions
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.
Interventions
PROCEDUREHepatic 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.
PROCEDUREUltrasound-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_TESTMultiparametric 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.
Sponsors
Universidade Federal do Rio de Janeiro
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Comparative study between diagnostic methods, with a cross-sectional design.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
Brazil
Contacts
Primary ContactGuilherme FM Rezende, MD, PhD
Backup ContactEduardo Sica, MD
Outcome results
None listed