Improvement of Portal Hypertension During Viral Suppression in Patients With Hepatitis Delta (IMPHROVE-D)

Study Overview
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Brief Summary
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Portal hypertension (PH) is one of the key drivers of clinical deteoration in patients with liver cirrhosis. It has been demonstrated that antiviral therapy in patients with chronic hepatitis C infection leads to a decrease of PH and is associated with an improved outcome. Recently, Bulevirtide was approved for the treatment of patients coinfected with hepatitis B (HBV) and chronic hepatitis delta (HDV) infection, which helps to achieve viral supression in these patients. This study investigates the potential effects of viral supression on PH in patients with chronic HBV/HDV infection and liver cirrhosis.

Official Title
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Improvement of Portal Hypertension During Viral Suppression in Patients With Hepatitis Delta (IMPHROVE-D)

Conditions
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Hepatitis D, Hepatitis B, Portal Hypertension, Liver Cirrhosis

Intervention / Treatment
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* Drug: Bulevirtide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic HBV/HDV Coinfection suspected or diagnosed liver cirrhosis, indication for hepatovenous pressure gradient (HVPG) measurement or liver cirrhosis and HVPG measurement conducted in the past 12 months (conducted prior to antiviral treatment) indication for antiviral treatment with Bulevirtide age >18years Must be willing to participate in the study and provide written informed consent Exclusion Criteria: patient rejects study participation no conducted or no indication for HVPG measurement age <18years
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 |
| --- | --- |
| One group with HBV/HDV coinfection<br>Measurement of HVPG before antiviral treatment of HBV/HDV coinfection and one year after treatment initiation with Bulevirtide. Administration of Bulevirtide and HVPG measurement is independent from this study. | Drug: Bulevirtide<br>* Patients with liver cirrhosis and HBV/HDV coinfection receive Bulevirtide as an antiviral therapy irrespective of the study, this study is observational.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change the degree of portal hypertension after inducing viral suppression via antiviral treatment with Bulevirtide | Change of hepatovenous pressure gradient (HVPG) in mmHg underviral suppression with Bulevirtide in patients with HBV/HDV coinfection and liver cirrhosis. HVPG measurement will be assessed via transjugular HVPG measurement. | Measurement before antiviral treatment (baseline) and one year after inducing viral suppression with Bulevirtide. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Quality of life under viral suppression with Bulevirtide | Change of Quality of life is assessed via SF-36 questionnaire. | Measurement before Bulevirtide intake (baseline) and one year after establishing antiviral treatment. | 
| Change in minimal hepatic encephalopathy (HE) status under viral suppression | Change in minimal HE status is evaluated via PSE-testing, critical flicker frequency and animal naming test. | Measurement before antiviral treatment (baseline) and one year after inducing viral suppression with Bulevirtide. | 
| Change of nutritional status under viral suppression with Bulevirtide | Change of nutritional status will be evaluated via repeated measurement of BMI (in kg/m2), arm circumference and triceps skin fold thickness. | Measurement before antiviral treatment (baseline) and one year after inducing viral suppression with Bulevirtide. | 
| Change of physical ability under viral suppression with Bulevirtide | Change of physical ability is assessed via liver-frailty Index. | Measurement before antiviral treatment (baseline) and one year after inducing viral suppression with Bulevirtide. | 
| Change of the inflammatory profile under viral suppression with Bulevirtide | Change of the inflammatory profile will be assessed through Cytokines using Bio-Plex Pro Human Cytokine Screening Panel, 48-Plex, Bio-Rad, Olink Target 96 Inflammation and Olink Proteomics. | Measurement before antiviral treatment (baseline) and one year after inducing viral suppression with Bulevirtide. | 
| Change in liver stiffness under viral suppression with Bulevirtide | Change in liver stiffness will be assessed via transient elastography. | Measurement before Bulevirtide intake (baseline) and one year after establishing antiviral treatment with Bulevirtide. | 
| Clinical endpoints under viral suppression with Bulevirtide | Assessed clinical endpoints are: Resolution of esophageal varices and incidence of esophageal bleeding, hepatic encephalopathy or ascites. | Measurement before antiviral treatment (baseline) and one year after inducing viral suppression with Bulevirtide. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Portal hypertension, Liver cirrhosis, Bulevirtide, Hepatitis D, Hepatitis B