Early virological response in six patients with hepatitis D virus infection and compensated cirrhosis treated with Bulevirtide in real‐life

Abstract

Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Bulevirtide (BLV, Hepcludex®) is an HDV/HBV entry inhibitor approved in June 2020 in the European Union for adult patients with chronic hepatitis delta (CHD) and compensated liver disease and positive HDV RNA viral load. This real‐life preliminary report described early virological efficacy and safety of BLV in six patients with CHD and compensated liver disease: four patients were treated with the combination of BLV (2 mg/d in subcutaneous injection) and pegylated interferon (PEG‐IFN) and two patients with BLV monotherapy. Four patients treated with combined therapy had a decline of a minimum of 1 log10 and 3/3 of 2 log10 of HDV‐VL at 12 and 24 weeks, respectively. One patient among four had stopped the treatment at 12 weeks because of thrombocytopenia and an HDV‐VL relapse was notified 24 weeks after treatment cessation. Three patients among four (3/4) had undetectable HDV‐VL during the therapy (<100 IU/ml). One patient (1/2) treated with BLV monotherapy had a decline of HDV‐VL by 1 log10 at 8 weeks and 1/1 by 2 log10 at 28 week on‐treatment. Two patients among four (2/4) with combined therapy had normal ALT reached at 4 and 56 weeks. One patient (1/2) with BLV monotherapy achieves ALT normalization at​ 4 weeks on treatment. Hepatitis B surface antigen (HBsAg) levels remain unchanged. Three among six (3/6) patients had an elevation of total biliary acids without pruritus. These early data generated confirm the interest in this new treatment. Final results will be important to demonstrate long‐term clinical benefit (fibrosis reversibility and reduction in hepato‐cellular carcinoma [HCC]).

Review article: emerging insights into the immunopathology, clinical and therapeutic aspects of hepatitis delta virus

“…Further results to demonstrate long-term clinical benefits will be key in the wider use of bulevirtide. 100 The EMA approved Hepcludex® at a dose of 2 mg subcutaneous per day for the treatment of chronic HDV infection in adult patients with compensated liver disease and positive HDV viremia. The optimal treatment duration has not been determined and treatment should be continued if a clinical benefit is observed with bulevirtide administration.…”

Signaling Induced by Chronic Viral Hepatitis: Dependence and Consequences

“…In contrast, chronic HBV infection can only be controlled by long-term antiviral strategies due to the persistence of cccDNA pools in patients’ liver [ 14 , 15 ]. For HDV, interferon-based therapies had only limited success; however, novel antivirals such as entry inhibitors have shown encouraging results in clinical practice to control HDV infection and to improve liver function [ 16 ]. Nevertheless, even if a viral infection is controlled or cured, the risk of developing HCC may not be fully reversed, depending on the duration of chronic infection, liver disease stage, and type of virus [ 17 , 18 ].…”

Hepatitis Delta virus in migrants: The challenge of elimination (ANRS CO22 HEPATHER cohort)

“…a maintenance therapy. 10 As daily BLV is administered by subcutaneous injection, it may not be well tolerated by some patients over the long term. Second, BLV needs to be refrigerated, which is not always possible given people's working conditions, travel commitments, and, in some cases, social precarity.…”

“…For instance, although preliminary results highlight the virological efficacy and safety of Bulevirtide (BLV) in patients with chronic HDV and compensated liver disease, 10 the logistical constraints associated with this treatment may impact adherence and treatment interruption in several ways: first, BLV uptake may require long‐term commitment by the patient; the optimal treatment duration has not yet been determined and accordingly BLV may be considered a maintenance therapy 10 . As daily BLV is administered by subcutaneous injection, it may not be well tolerated by some patients over the long term.…”