Case Report| Volume 71, ISSUE 4, P834-839, October 2019

Excellent safety and effectiveness of high-dose myrcludex-B monotherapy administered for 48 weeks in HDV-related compensated cirrhosis: A case report of 3 patients


      Short-term administration of the entry inhibitor myrcludex-B (MyrB) has been shown to be safe and effective in phase II studies in patients coinfected with hepatitis B virus (HBV) and hepatitis delta virus (HDV). However, its effectiveness and safety are unknown during long-term and high-dose treatment of patients with compensated cirrhosis in real-life settings. Herein, we describe the first 3 European patients with HDV-related compensated cirrhosis who were treated with MyrB 10 mg/day for 48 weeks as a compassionate therapy. Liver function tests, bile acids, and virological markers were monitored every 4 weeks. HBV/HDV-specific T cell quantity (up to 48 and 36 weeks) and HBV RNA levels were also assessed in 2 cases. During MyrB treatment, HDV RNA levels progressively declined from 4.4 and 5.6 logs IU/ml to undetectability in 2 cases, and from 6.8 log copies/ml to 500 copies/ml for the other patient. Alanine aminotransferase normalised after 20, 12 and 28 weeks, respectively. A significant improvement in features of portal hypertension, liver function tests and alpha-fetoprotein levels were documented in 2 cases. In the male patient with histological and clinical stigmata of autoimmune hepatitis, IgG and immunoglobulins rapidly normalised. No significant changes in HBV surface antigen levels and circulating HBV/HDV-specific T cells were demonstrated; HBV DNA and HBV RNA levels remained undetectable throughout the study period. MyrB was well tolerated; patients remained fully asymptomatic despite a significant increase of bile acids. In conclusion, this report shows excellent safety and effectiveness of a 48-week course of MyrB 10 mg/day, combined with tenofovir disoproxil fumarate, for the treatment of HDV-related compensated cirrhosis.


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        • Wedemeyer H.
        • Yurdaydin C.
        • Ernst S.
        • Caruntu F.A.
        • Curescu M.G.
        • Yalcin K.
        • et al.
        Peginterferon alfa-2 a plus tenofovir disoproxil fumarate for hepatitis D (HIDIT-II): a randomised, placebo controlled, phase 2 trial.
        Lancet Infect Dis. 2019; 19: 275-286
        • Lempp F.A.
        • Urban S.
        Hepatitis Delta virus: replication strategy and upcoming therapeutic options for a neglected human pathogen.
        Viruses. 2017; 9
        • Bogomolov P.
        • Alexandrov A.
        • Voronkova N.
        • Macievich M.
        • Kokina K.
        • Petrachenkova M.
        • et al.
        Treatment of chronic hepatitis D with the entry inhibitor myrcludex B: First results of a phase Ib/IIa study.
        J Hepatol. 2016; 65: 490-498
        • Wedemeyer H.
        • Bogomolov P.
        • Blank A.
        • Allweiss L.
        • Dandri-Petersen M.
        • Bremer B.
        • et al.
        Final results of a multicenter, open-label phase 2b clinical trial to assess safety and efficacy of Myrcludex B in combination with tenofovir in patients with chronic HBV/HDV co-infection.
        J Hepatol. 2018; 68: S3
        • Wedemeyer H.
        • Schöneweis K.
        • Bogomolov P.
        • Voronkova N.
        • Chulanov V.
        • Stepanova T.
        • et al.
        Interim results of a multicentre, open-label phase 2 clinical trial (MYR203) to assess safety and efficacy of Myrcludex B in combination with Peg-Interferon alpha 2a in patients with chronic HBV/HDV co-infection.
        Hepatology. 2018; 68: S11A
        • Blank A.
        • Eidam A.
        • Haag M.
        • Hohmann N.
        • Burhenne J.
        • Schwab M.
        • et al.
        The NTCP-inhibitor Myrcludex B: effects on bile acid disposition and tenofovir pharmacokinetics.
        Clin Pharmacol Ther. 2018; 103: 341-348
        • Loglio A.
        • Segato S.
        • Lampertico P.
        Hepatitis D – how is the fight against this foe going?.
        Expert Rev Clin Pharmacol. 2019; 12: 169-171
        • Yurdaydin C.
        • Abbas Z.
        • Buti M.
        • Cornberg M.
        • Esteban R.
        • Etzion O.
        • Gane E.J.
        • et al.
        Treating chronic hepatitis delta: the need for surrogate markers of treatment efficacy.
        J Hepatol. 2019; 70: 1008-1015
        • Zhao K.
        • Liu S.
        • Chen Y.
        • Yao Y.
        • Zhou M.
        • Yuan Y.
        • et al.
        Upregulation of HBV transcription by sodium taurocholate cotransporting polypeptide at the postentry step is inhibited by the entry inhibitor Myrcludex B.
        Emerg Microbes Infect. 2018; 7: 186
        • Khakpoor A.
        • Ni Y.
        • Chen A.
        • Ho Z.Z.
        • Oei V.
        • Yang N.
        • et al.
        Spatiotemporal differences in presentation of CD8 T cell epitopes during hepatitis B virus infection.
        J Virol. 2019; 5