Effectiveness and Safety of Bulevirtide (BLV) Therapy in Patients With Chronic Hepatitis Delta (CHD) in Italy (D-SHIELD)

Study Overview
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Brief Summary
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Multicenter pharmacological observational prospective, no-profit, study. This study was designed to get a real-life snapshot across several Italian Hepatology centers. All HDV patients are followed up according to EASL 2017 guidelines. This allows uniformity on the indication for antiviral treatment and management of that antiviral therapy. No off-label medications are used. All data are retrievable from the patient's medical record. In addition, clinical and biochemical data from patients at month 0, 1, 2, 4, 6 and 12 of treatment, and otherwise within the study period, will be collected longitudinally. The primary objective of the study is to describe the virological response to BLV in all patients starting BLV therapy for CHD, defined as a >2 Log decline in HDV-RNA or undetectable HDV-RNA (using the Robogene 2.0 quantitative kit, LLQ <6 IU/ml) at month 12 of therapy. HDV patients who will start therapy with BLV 2 mg/day from May 2023, according to AIFA guidelines, will be consecutively enrolled.

Official Title
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Effectiveness and Safety of Bulevirtide (BLV) Therapy in Patients With Chronic Hepatitis Delta (CHD) in Italy: a Multicenter Prospective Real Life Data Study

Conditions
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Hepatitis D

Intervention / Treatment
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* Drug: Bulevirtide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Chronic hepatitis delta Compensated cirrhosis HDV related Patients who will start therapy with BLV 2 mg/day from May 2023 Exclusion Criteria: HDV-related decompensated cirrhosis (CPT ≥7)

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 |
| --- | --- |
| Hepatis Delta<br>Bulevirtide (BLV) at a dose of 2 mg/day subcutaneously | Drug: Bulevirtide<br>* dose of 2 mg/day subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Describe the virological response to BLV in all patients starting BLV therapy for CHD | Percentage of patients with undetectable HDV RNA | Month 6 | 
| Describe the virological response to BLV in all patients starting BLV therapy for CHD | Percentage of patients with ≥ 2 log IU/ml decline of HDV RNA | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the proportion of patients with virological response, defined as a >2 Log decline in HDV-RNA | Proportion of patients with virological response, defined as a >2 Log decline in HDV-RNA | Month 6 | 
| Evaluation of the proportion of patients with virological response, defined as a >2 Log decline in HDV-RNA | Proportion of patients with virological response, defined as a >2 Log decline in HDV-RNA | Month 12 | 
| Evaluation of the proportion of patients with virological response, defined as undetectable HDV-RNA | Proportion of patients with virological response, defined as undetectable HDV-RNA | Month 6 | 
| Evaluation of the proportion of patients with virological response, defined as undetectable HDV-RNA | Proportion of patients with virological response, defined as undetectable HDV-RNA | Month 12 | 
| Evaluation of the percentage of patients with >2 Log decrease in HDV-RNA along with normalization of ALT | Percentage of patients with >2 Log decrease in HDV-RNA along with normalization of ALT | Month 6 | 
| Evaluation of the percentage of patients with >2 Log decrease in HDV-RNA along with normalization of ALT | Percentage of patients with >2 Log decrease in HDV-RNA along with normalization of ALT | Month 12 | 
| Evaluation of the percentage of patients with normal ALT | Percentage of patients with normal ALT | Month 6 | 
| Evaluation of the percentage of patients with normal ALT | Percentage of patients with normal ALT | Month 12 | 
| Evaluation of the percentage of patients with clinical response, i.e., the percentage of patients who remain free of liver complications, such as HCC or decompensation | Percentage of patients who remain free of liver complications (de novo HCC or onset of decompensation) | Month 6 | 
| Evaluation of the percentage of patients with clinical response, i.e., the percentage of patients who remain free of liver complications, such as HCC or decompensation | Percentage of patients who remain free of liver complications (de novo HCC or onset of decompensation) | Month 12 | 
| Investigation of changes over time in serum levels of HBsAg (UI/mL) | Change in serum levels of HBsAg- by medians and ranges | Month 6 | 
| Investigation of changes over time in serum levels of HBsAg (UI/mL) | Change in serum levels of HBsAg- by medians and ranges | Month 12 | 
| Investigation of changes over time in serum levels of albumin (g/dL) | Change in serum levels albumin- by medians and ranges | Month 6 | 
| Investigation of changes over time in serum levels of albumin (g/dL) | Change in serum levels albumin- by medians and ranges | Month 12 | 
| Investigation of changes over time in serum levels of platelets (10e9/L) | Change in serum levels of platelets - by medians and ranges | Month 6 | 
| Investigation of changes over time in serum levels of platelets (10e9/L) | Change in serum levels of platelets - by medians and ranges | Month 12 | 
| Investigation of changes over time in serum levels of AFP (µg/L) | Change in serum levels of AFP - by medians and ranges | Month 6 | 
| Investigation of changes over time in serum levels of AFP (µg/L) | Change in serum levels of AFP - by medians and ranges | Month 12 | 
| Evaluation of treatment safety | Occurrence of change in serum bile acid levels (µmol/L) | Month 6 | 
| Evaluation of treatment safety | Occurrence of adverse events | Month 6 | 
| Evaluation of treatment safety | Occurrence of change in serum bile acid levels (µmol/L) | Month 12 | 
| Evaluation of treatment safety | Occurrence of adverse events | Month 12 |