Efficacy and Safety of Bulevirtide plus Tenofovir Disoproxil Fumarate in Real-World Patients with Chronic Hepatitis B and D Co-Infection

Herta, Toni; Hahn, Magdalena; Maier, Melanie; Fischer, Janett; Niemeyer, Johannes; Hönemann, Mario; Böhlig, Albrecht; Gerhardt, Florian; Schindler, Aaron; Schumacher, Jonas; Berg, Thomas

doi:10.3390/pathogens11050517

Cited by 24 publications

(13 citation statements)

References 28 publications

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“…Phase II studies and the Week 24 interim analysis of phase III study demonstrated the efficacy and safety of antiviral treatment with bulevirtide as a monotherapy or combined with PEG‐IFNα 19–23 . BLV reduces HDV replication and normalizes ALT levels in the majority of treated patients with compensated chronic hepatitis delta which has recently been confirmed in first real‐world data from Austria, Italy, France and Germany 23–28 . Importantly, BLV treatment is generally well tolerated with local injection side reactions being the most frequent symptoms 23 …”

Section: Introductionmentioning

confidence: 89%

“…[19][20][21][22][23] BLV reduces HDV replication and normalizes ALT levels in the majority of treated patients with compensated chronic hepatitis delta which has recently been confirmed in first real-world data from Austria, Italy, France and Germany. [23][24][25][26][27][28] Importantly, BLV treatment is generally well tolerated with local injection side reactions being the most frequent symptoms. 23 As NTCP is a bile acid transporter, one would expect a dosedependent increase of bile acids during BLV treatment.…”

Section: Introductionmentioning

confidence: 99%

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Bile acid increase during bulevirtide treatment of hepatitis D is not associated with a decline in HDV RNA

Deterding

Port

et al. 2023

Journal of Viral Hepatitis

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Bulevirtide (BLV) is an entry inhibitor blocking entry of HBsAg into hepatocytes by interfering with the bile acid transporter Na+‐taurocholate co‐transporting polypeptide. We here investigated if bile acid levels before or during BLV treatment would correlate with HDV RNA declines. We studied 20 patients with compensated HDV infection receiving a daily dose of 2 mg bulevirtide subcutaneously qd for at least 24 weeks. ALT levels improved in all patients including 13/20 patients showing normal ALT values at treatment Week 24. An HDV RNA drop of at least 50% was evident in 20/20 patients at Week 24 including 10 patients showing a ≥ 2 log HDV RNA decline. Elevated bile acid levels were detected already before treatment in 10 patients and further increased during BLV administration with different kinetics. Baseline bile acids were associated with higher transient elastography values (p = .0029) and evidence of portal hypertension (p = .0004). Bile acid levels before treatment were associated with HDV RNA declines throughout therapy, but not at Week 24 (rho = −0.577; p = .0078; rho = −0.635, p = .0026; rho = −0.577, p = .0077; rho = −0.519, p = .0191; rho = −0.564, p = .0119 and rho = −0.393, p = .087 at treatment Weeks 2, 8, 12, 16, 20 and 24, respectively). However, bile acid increases during treatment were not associated with HDV RNA or ALT declines at any of the time points. BLV‐induced increases in bile salts do not correlate with HDV RNA declines suggesting that the inhibitory effects of BLV on NTCP differ between blocking bile acid transport and hindering HBsAg entry. If baseline bile salt levels could be useful to predict virological response remains to be confirmed.

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Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Bile acid increase during bulevirtide treatment of hepatitis D is not associated with a decline in HDV RNA

Deterding

Port

et al. 2023

Journal of Viral Hepatitis

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“…Three instances had extended treatment data>48 w available; two of them showed ongoing virologic and biochemical responses, while the third showed an HDV-RNA breakthrough. There were no adverse effects noted [26].…”

Section: Clinical Studiesmentioning

confidence: 82%

Novel Entry Inhibitors for Viral Hepatitis D Treatment: Bulevirtide

MISRA²

2023

Int J Curr Pharm Sci

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Chronic hepatitis D virus infection is the most severe form of viral hepatitis. Hepatitis delta virus (HDV) is a faulty RNA virus that needs hepatitis B virus surface antigen (HBsAg) for the completion of its life cycle. Hepatitis B virus (HBV) receptor, sodium taurocholate cotransporting polypeptide (NTCP), is used by HDV to infect hepatocytes. The replication of the HDV genome, which is a circular single-stranded RNA and encodes for a single HDAg that occurs in two forms (S-HDAg and L-HDAg), is carried out by the host RNA polymerases. Antiviral therapy is urgently needed to protect patients from hepatocellular carcinoma or end-stage liver disease and poses an important public health issue in many countries. There is still a need for efficient pharmacological therapies for chronic hepatitis D (CHD). A good strategy to stop new infections is to stop virus from entering cells. A new virion entry inhibitor called bulevirtide is now a promising treatment for both infections because it prevents the virion from entering the hepatocyte through the hepatic sodium/taurocholate cotransporting polypeptide Before bulevirtide's conditional approval by the EMA (European Medicines Agency) in July 2020 for the treatment of chronic HDV infection in adult patients with compensated liver disease, therapy options were restricted to the off-label use of pegylated interferon alfa. (NTCP) receptor. We will outline the most recent discoveries about the HDV life cycle that have prompted the development of noveldrug bulevirtide.

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“…Germany also reported long‐term outcomes at Weeks 52, 56 and 68 in three patients receiving BLV 2 mg/day monotherapy. All patients achieved a virological response at Week 24, that was maintained throughout Week 68 in two cases, while the other experienced HDV RNA breakthrough at Week 40 16 …”

Section: Blv Monotherapymentioning

confidence: 98%

Bulevirtide‐based treatment strategies for chronic hepatitis delta: A review

Degasperi

Lampertico

2023

Journal of Viral Hepatitis

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Chronic hepatitis Delta (CHD) is a rare and severe form of chronic viral hepatitis.Until recently, the only therapeutic approach has been the off-label use of a 48 weeks course of PegInterferon alpha (PegIFNα), that was characterized by suboptimal efficacy and burdened by significant side effects that limited treatment applicability in patients with advanced liver disease. In July 2020, European Medicines Agency (EMA) conditionally approved the entry inhibitor Bulevirtde (BLV) at the dose of 2 mg/day for the treatment of adult patients with compensated CHD. Efficacy and safety of BLV in CHD have been evaluated in clinical trials either as monotherapy or in combination with PegIFNα. These results were confirmed by real-life studies, which also evaluated long-term BLV monotherapy in patients with advanced compensated cirrhosis. Notwithstanding these promising results there are still several issues to be addressed, such as the optimal duration of the treatment, the rates of off-therapy responses, as well as the long-term clinical benefits. This review summarizes updated and current literature data about clinical trials and real-life studies with BLV monotherapy and/or in combination with PegIFNα.

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Efficacy and Safety of Bulevirtide plus Tenofovir Disoproxil Fumarate in Real-World Patients with Chronic Hepatitis B and D Co-Infection

Cited by 24 publications

References 28 publications

Bile acid increase during bulevirtide treatment of hepatitis D is not associated with a decline in HDV RNA

Bile acid increase during bulevirtide treatment of hepatitis D is not associated with a decline in HDV RNA

Novel Entry Inhibitors for Viral Hepatitis D Treatment: Bulevirtide

Bulevirtide‐based treatment strategies for chronic hepatitis delta: A review

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