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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Common Variable Immunodeficiency; Non-Cirrhotic Portal Hypertension
• Intervention / Treatment: Diagnostic test: Ultrasound including color doppler ultrasound

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Dominik Bettinger, MD; Phone Number: +49761270-36870; Email: dominik.bettinger@uniklinik-freiburg.de
• Study Contact Backup: Name: Marlene Reincke, MD; Phone Number: +49761270-34010; Email: marlene.reincke@uniklinik-freiburg.de

Study Locations

• Germany
  • Freiburg, Germany, 79106
    • Recruiting
    • University Medical Center Freiburg, Department of Medicine II
    • Principal Investigator: Dominik Bettinger, MD
    • Sub-Investigator: Michael Schultheiss, MD
    • Contact: Dominik Bettinger, MD; Phone Number: +49761270-36870; Email: dominik.bettinger@uniklinik-freiburg.de
    • Contact: Marlene Reincke, MD; Phone Number: +49761270-34010; Email: marlene.reincke@uniklinik-freiburg.de
    • Principal Investigator: Marlene Reincke, MD
    • Principal Investigator: Klaus Warnatz, MD
    • Sub-Investigator: Patrick Bez, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with CVID will be included in the study. Patients will be divided into three subgroups: 1) Patients with CVID and autoimmunity, but no liver involvement (n=75) 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 (n=75) 3) Patients with CVID and clinically significant non-cirrhotic portal hypertension (n=75).

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 (n=25)

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with CVID and autoimmunity and no liver involvement.; Patients with CVID and autoimmune disease, but no liver involvement (normal liver enzymes and normal abdominal ultrasound)	Diagnostic test: Ultrasound including color doppler ultrasound; 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.; Other Names: Liver stiffness measurement by transient elastography; Spleen stiffness measurement by transient elastography
Patients with CVID and liver involvement and no clinical significant portal hypertension; 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; 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.; Other Names: Liver stiffness measurement by transient elastography; Spleen stiffness measurement by transient elastography
Patients with CVID and clinically significant non-cirrhotic portal hypertension; 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; 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.; Other Names: Liver stiffness measurement by transient elastography; Spleen stiffness measurement by transient elastography

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital Freiburg
• Investigators: Principal Investigator: Dominik Bettinger, MD, University Hospital Freiburg; Principal Investigator: Klaus Warnatz, MD, University Hospital Freiburg; Principal Investigator: Marlene Reincke, MD, University Hospital Freiburg

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 10, 2023
• First Submitted That Met QC Criteria: November 21, 2023
• First Posted (Actual): November 22, 2023

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: ultrasound; Common Variable Immunodeficiency; liver stiffness measurement; non-cirrhotic portal hypertension; spleen stiffness measurement
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Liver Diseases; Hypertension; Immunologic Deficiency Syndromes; Hypertension, Portal; Common Variable Immunodeficiency
• Other Study ID Numbers: CVID-pHT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No