1. In this randomized controlled trial, 48 weeks of buleviritide treatment resulted in reduced hepatitis D ribonucleic acid (RNA) levels in patients with chronic hepatitis D.
2. The buleviritide group also had lower alanine transaminase (ALT) levels as compared to controls.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Hepatitis D virus (HDV) is an RNA virus that requires hepatitis B surface antigen for entry into hepatocytes and for propagation. HDV infection is estimated to affect between 10 million and 20 million individuals worldwide. While oral antiviral drugs currently available for the treatment of hepatitis B virus (HBV) infection are effective as monotherapy in suppressing HBV replication, they do not effectively suppress HDV replication. Bulevirtide has been proposed to inhibit the entry of HBV and HDV into hepatocytes, and in a phase two trial was shown to induce pronounced declines in HDV RNA and ALT levels. However, there is a gap in knowledge as to understanding the prolonged effect of bulevirtide in terms of efficacy and safety in patients with chronic hepatitis D. Overall, this study found that a combined response at week 48 occurred in a significantly greater percentage of patients in the bulevirtide groups than in the control group. This study was limited by not blinding trial-group assignment, and not all HDV and HBV genotypes were represented. Nevertheless, these study’s findings are significant, as they demonstrate that after 48 weeks of bulevirtide treatment, HDV RNA and ALT levels were reduced in patients with chronic hepatitis D.
Click to read the study in NEJM
Relevant Reading: New Approaches to Chronic Hepatitis B
In-Depth [open-label randomized trial]: This multicenter, open-label, randomized trial was conducted on eligible chronic hepatitis D patients. Participants were randomized in a 1:1:1 ratio to receive immediate subcutaneous treatment with bulevirtide at 2mg per day (one injection; 2mg group), bulevirtide at 10 mg per day (two injections; 10-mg group) for 144 weeks, or to receive no treatment for 48 weeks followed by subcutaneous treatment with bulevirtide at 10 mg per day for 96 weeks (control group). Patients who were 18 to 65 years old, had chronic hepatitis D for at least six months, and had an ALT level of more than one times but less than 10 times the upper limit of the normal range at screening were eligible for the study. Patients who had decompensated cirrhosis, receipt of interferon therapy within 6 months before screening, and a platelet count of less than 60,000 cells per cubic millimeter were excluded from the study. The primary outcome measured was a combined response at week 48 of an undetectable HDV RNA level or a level that decreased by at least 2 log10 IU per milliliter from baseline (virologic response), and normalization of the ALT level (biochemical response). Based on the primary analysis, a primary end-point response occurred in 45% of patients in the 2mg group, 48% in the 10mg group, and 2% in the control group (p<0.001 for the comparison of each dose group with the control group). The HDV RNA level at week 48 was undetectable in 12% of patients in the 2mg group and in 20% in the 10mg group (p=0.41). The ALT level normalized in 12% of patients in the control group, 51% in the 2mg group (difference from control, 39%; 95% Confidence Interval [CI], 20 to 56), and 56% in the 10mg group (difference from control, 44%; 95% CI, 26 to 60). In summary, this study demonstrates that bulevirtide treatment can reduce HDV RNA and ALT levels in patients with chronic hepatitis D.
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