Impact of Handling Perception and Language Barriers on Virologic Response to Daily Subcutaneous Bulevirtide in Hepatitis D

BACKGROUND: Bulevirtide (BLV) is the only approved therapy for chronic hepatitis D (CHD) and compensated liver disease. Daily subcutaneous injection and the need for refrigeration may pose challenges, especially in patients with limited language proficiency. AIMS: Assessment of patient-reported BLV handling and satisfaction and association with virologic response. METHODS: Patients receiving BLV were assessed using a structured questionnaire on injection preparation, administration, refrigeration, adverse effects, and language proficiency. Virologic response was defined as complete (≥ 2 log10 reduction from baseline or HDV RNA undetectable), intermediate (≥ 1 log10 but < 2 log10 reduction), non-response (< 1 log10 reduction or increase), or breakthrough (> 1 log10 increase after ≥ 2 log10 reduction). RESULTS: A total of 115 patients from 30 countries were recruited at 12 German centres. German language skills were rated as good, sufficient, poor or absent in 58%, 25% and 17% of cases. Reported difficulties included injection preparation (17%), administration (25%) and refrigeration (27%). Patients without virologic response or with viral breakthrough reported difficulties with injection administration in 56% compared to 17% with intermediate or complete response (p = 0.0002), while no differences were observed regarding preparation or refrigeration. Injection site reactions occurred in 57% of patients. Overall, 82% were satisfied with the practical handling and 94% with the tolerability of BLV. Good language proficiency was associated with greater satisfaction with the practical handling (p = 0.0067), which in turn correlated with virologic response (p = 0.0001). CONCLUSIONS: BLV administration is generally well manageable. Limited language proficiency and injection difficulties may negatively affect patient satisfaction and potentially influence treatment outcomes. TRIAL REGISTRATION: German Clinical Trials Registry (DRKS 00033153).