Prediction of Portal Hypertension in Patients With CVID (CVID-pHT)

Study Overview
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Brief Summary
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Patients with CVID will be offered to participate in this observational trial during the routine annual visit in the outpatient clinic at the Center of chronic Immunodeficiency (CCI) of the University Medical Center Freiburg, Germany. Clinical and laboratory data at the time of presentation will be assessed. Additionally, parameters of abdominal ultrasound, duplex sonography of the liver and spleen, and liver and spleen stiffness at the time of presentation will be evaluated. If applicable, clinical and/or interventional parameters indicating clinically significant portal hypertension (i.e. presence of varices or portal-hypertensive gastropathy in esophago-gastroduodenoscopy, presence of ascites) within 12 months prior and after the index visit will be assessed. During the visit, serum/plasma samples and peripheral blood mononuclear cells (PBMC) are collected and stored in an associated biobank.

Detailed Description
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Patients with CVID can be included in the study. The study cohort will consist of three subgroups: 1) Patients with CVID and autoimmunity, but no liver involvement. 2) Patients with CVID and liver involvement, defined by elevated liver enzymes, abnormal ultrasound and/or abnormal liver biopsy, but no signs of clinically significant portal hypertension and 3) Patients with CVID and clinically significant non-cirrhotic portal hypertension. Further, patients with CVID and diagnosed non-cirrhotic portal hypertension between 01/01/2004 and the start of the prospective part of this study (01/01/2023) will be included retrospectively in this study. Patients will be recruited during the routine annual visit in the outpatient clinic at the Center of chronic Immunodeficiency (CCI) of the University Medical Center Freiburg, Germany. During the visit a standard ultrasound protocol, including size and morphology of liver and spleen, duplex-sonography of the liver, and measurement of liver and spleen stiffness via transient elastography will be performed as a part of the routine clinical diagnostic. Results from endoscopy or other interventions (esophago-gastroduodenoscopy, invasive measurement of hepatic venous-portal pressure gradient, or TIPS implantation, if applicable) within 12 months prior and after the index visit will be assessed. All non-invasive and invasive interventions will be conducted solely based on clinical decisions made independently from the study inclusion as the study is designed as an observational study. Detailed patient characteristics, epidemiologic, clinical, imaging and laboratory parameters will be assessed and included in an electronic database. Apart from these data, patients will be asked to participate in biobank sampling including serum/plasma and peripheral blood mononuclear cells (PBMC) samples from the peripheral veins. All patients recruited in this study will be followed-up for at least 12 months. Outcome parameters include parameters from abdominal ultrasound, duplex-sonography and stiffness of liver and spleen, presence or development of clinically significant portal hypertension and non-invasive fibrosis scores based on laboratory and ultrasound parameters.

Official Title
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Evaluation of Ultrasound Parameters and Liver and Spleen Stiffness for Prediction of Clinically Significant Portal Hypertension in Patients With Common Variable Immunodeficiency Syndrome

Conditions
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Non-Cirrhotic Portal Hypertension, Common Variable Immunodeficiency

Intervention / Treatment
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* Diagnostic Test: Ultrasound including color doppler ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with CVID Exclusion Criteria: no written informed consent concomitant chronic liver disease (viral hepatitis, alcoholic liver disease, steatitic liver disease, hemochromatosis, primary biliary cholangitis, primary sclerosis cholangitis, M. Wilson, alpha-1-antitrypsin deficiency)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with CVID and autoimmunity and no liver involvement.<br>Patients with CVID and autoimmune disease, but no liver involvement (normal liver enzymes and normal abdominal ultrasound) | Diagnostic Test: Ultrasound including color doppler ultrasound<br>* Patients with CVID receive color doppler ultrasound of the liver including assessment of portal vein diameter, portal vein flow velocity, hepatic vein diameter and assessment of arterial perfusion. Further liver and spleen stiffness measurement by transient elastography is performed.<br>* Other names: Spleen stiffness measurement by transient elastography;|
| Patients with CVID and liver involvement and no clinical significant portal hypertension<br>Patients with CVID and liver involvement (elevated liver enzymes, abnormal ultrasound and/or abnormal liver biopsy), but no clinically significant portal hypertension | Diagnostic Test: Ultrasound including color doppler ultrasound<br>* Patients with CVID receive color doppler ultrasound of the liver including assessment of portal vein diameter, portal vein flow velocity, hepatic vein diameter and assessment of arterial perfusion. Further liver and spleen stiffness measurement by transient elastography is performed.<br>* Other names: Spleen stiffness measurement by transient elastography;|
| Patients with CVID and clinically significant non-cirrhotic portal hypertension<br>Patients with CVID and clinically significant non-cirrhotic portal hypertension (indicated by the presence of ascites or esophageal varices / portal-hypertensive gastropathy). | Diagnostic Test: Ultrasound including color doppler ultrasound<br>* Patients with CVID receive color doppler ultrasound of the liver including assessment of portal vein diameter, portal vein flow velocity, hepatic vein diameter and assessment of arterial perfusion. Further liver and spleen stiffness measurement by transient elastography is performed.<br>* Other names: Spleen stiffness measurement by transient elastography;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in liver stiffness between CVID patients with and without liver involvement and with clinically significant portal hypertension. | Liver stiffness will be assessed by transient elastography. | Study inclusion, after 12 months | 
| Differences in spleen stiffness between CVID patients with and without liver involvement and with clinically significant portal hypertension. | Spleen stiffness will be assessed by transient elastography. | Study inclusion, after 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in portal vein diameter between CVID patients with and without liver involvement and with clinically significant portal hypertension. | Portal vein diameter will be assessed by color doppler ultrasound | Study inclusion, after 12 months | 
| Differences in portal vein flow velocity between CVID patients with and without liver involvement and with clinically significant portal hypertension. | Portal vein flow velocity will be assessed by color doppler ultrasound | Study inclusion, after 12 months | 
| Differences in alanine aminotransfersases (ALT) between CVID patients with and without liver involvement and with clinically significant portal hypertension. | ALT is assessed during routine clinical practice | Study inclusion, after 12 months | 
| Differences in aspartat aminotransfersases (AST) between CVID patients with and without liver involvement and with clinically significant portal hypertension. | AST is assessed during routine clinical practice | Study inclusion, after 12 months | 
| Differences in liver function tests (bilirubin, albumin, INR) between CVID patients with and without liver involvement and with clinically significant portal hypertension. | Liver function liver function tests (bilirubin, albumin, INR) are assessed during routine clinical practice | Study inclusion, after 12 months | 
| Differences in platelets between CVID patients with and without liver involvement and with clinically significant portal hypertension. | Platelets are assessed during routine clinical practice | Study inclusion, after 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-cirrhotic portal hypertension, Common Variable Immunodeficiency, ultrasound, liver stiffness measurement, spleen stiffness measurement