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Review

Investigational drugs in development for Hepatitis D

Pages 999-1005 | Received 23 Jan 2017, Accepted 17 Jul 2017, Published online: 28 Jul 2017

References

  • Rizzetto M. Hepatitis D: thirty years after. J Hepatol. 2009;50:1043–1050.
  • Taylor JM. Virology of hepatitis D virus. Semin Liver Dis. 2012;32:195–200.
  • Rizzetto M, Verme G, Recchia S, et al. Chronic hepatitis in carriers of hepatitis B surface antigen, with intrahepatic expression of the delta antigen. An active and progressive disease unresponsive to immunosuppressive treatment. Ann Intern Med. 1983;98:437–441.
  • Niro GA, Rosina F, Rizzetto M. Treatment of hepatitis D. J Viral Hepat. 2005;12:2–9.
  • Rasshofer R, Choi SS, Wolfl P, et al. Interference of antiviral substances with replication of hepatitis delta virus RNA in primary woodchuck hepatocytes. Prog Clin Biol Res. 1991;364:223–234.
  • Farci P. Treatment of chronic hepatitis D: new advances, old challenges. Hepatology. 2006;44:536–539.
  • Ciancio A, Rizzetto M. PEG-IFN for the treatment of hepatitis D. Nat Rev Gastroenterol Hepatol. 2011;8:304–306.
  • Abbas Z, Khan MA, Salih M, et al. Interferon alpha for chronic hepatitis D. Cochrane Database Syst Rev. 2011 Dec 7;(12). Doi: 10.1002/14651858, CDC006002.pub2
  • Ciancio A, Rizzetto M. Chronic hepatitis D at a standstill: where do we go from here? Nat Rev Gastroenterol Hepatol. 2014;11:68–71.
  • Wedemeyer H, Yurdaydìn C, Dalekos GN, et al. HIDIT Study Group. Peginterferon plus adefovir versus either drug alone for hepatitis delta. N Engl J Med. 2011;364:322–331.
  • Heidrich B, Yurdaydin C, Kabacam G, et al. Late HDV RNA relapse after peginterferon alpha-based therapy of chronic hepatitis delta. Hepatology. 2014;60:87–97.
  • Yurdaydin C. Treatment of chronic delta hepatitis. Semin Liver Dis. 2012;32:237–244.
  • Lai MM. RNA replication without RNA-dependent RNA polymerase: surprises from hepatitis delta virus. J Virol. 2005;79:7951–7958.
  • Urban S, Bartenschlager R, Kubitz R, et al. Strategies to inhibit entry of HBV and HDV into hepatocytes. Gastroenterology. 2014;147:48–64.
  • Casey JL. RNA editing in hepatitis delta virus. Curr Top Microbiol Immunol. 2006;307:67–89.
  • Huang WH, Chen CW, Wu HL, et al. Post-translational modification of delta antigen of hepatitis D virus. Curr Top Microbiol Immunol. 2006;307:91–112.
  • Glenn JS, Watson JA, Havel CM, et al. Identification of a prenylation site in delta virus large antigen. Science. 1992;256(5061):1331–1333.
  • Glenn JS. Prenylation of HDAg and antiviral drug development. Curr Top Microbiol Immunol. 2006;307:133–149.
  • Bordier BB, Marion PL, Ohashi K, et al. A prenylation inhibitor prevents production of infectious hepatitis delta virus particles. J Virol. 2002;76:10465–10472.
  • Bordier BB, Ohkanda J, Liu P, et al. In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus. J Clin Investig. 2003;112:407–414.
  • Berndt N, Hamilton AD, Sebti SM. Targeting protein prenylation for cancer therapy. Nat Rev Cancer. 2011;11:775–791.
  • Koh C, Canini L, Dahari H, et al. Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial. Lancet Infect Dis. 2015;15:1167–1174.
  • Ghosal A, Chowdhury SK, Tong W, et al. Identification of human liver cytochrome P450 enzymes responsible for the metabolism of Lonafarnib (Sarasar). Drug Met Disp. 2006;34:628–635.
  • Yurdaydin C, Idilman R, Kalkan C, et al. Exploring optimal dosing of Lonafarnib with Ritonavir for the treatment of chronic delta hepatitis-interim results from the lowr hdv-2 study. Hepatology. 2016;64:abstract: 1845,910A.
  • Wedemeyer H, Port K, Deterding K, et al. A phase 2 study of titrating dose Lonafarnib plus Ritonavir in patients with chronic hepatitis D: interim results from the Lonafarnib with Ritonavir in HDV-4 study. AASLD. Hepatology. 2016;64:abstract 230, 121.
  • Ni Y, Lempp FA, Mehrle S, et al. Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species- specific entry into hepatocytes. Gastroenterology. 2014;146:1070–1083.
  • Blanchet M, Sureau C, Labonté P. Use of FDA approved therapeutics with hNTCP metabolic inhibitory properties to impair the HDV lifecycle. Antiviral Res. 2014;106:111–115.
  • Nkongolo S, Yi N, Lempp FA, et al. Cyclosporin A inhibits hepatitis B and hepatitis D virus entry by cyclophilin- independent interference with the NTCP receptor. J Hepatol. 2014;60:723–731.
  • Shimura S, Watashi K, Fukano K, et al. Cyclosporin derivatives inhibit hepatitis B virus entry without interfering with NTCP transporter activity. J Hepatol. 2017;66:685–692.
  • Lempp FA, Ni Y, Urban S. Hepatitis delta virus: insights into a peculiar pathogen and novel treatment options. Nat Rev Gastroenterol Hepatol. 2016;13:580–589.
  • Gripon P, Cannie I, Urban S. Efficient inhibition of hepatitis B virus infection by acylated peptides derived from the large viral surface protein. J Virol. 2005;79:1613–1622.
  • Blank A, Markert C, Hohmann N, et al. First-in-human application of the novel hepatitis B and hepatitis D virus entry inhibitor myrcludex. B J Hepatol. 2016;65:483–489.
  • Bogomolov P, Alexandrov A, Voronkova N, 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.
  • Bogomolov P, Voronkova N, Schoeneweis K, et al. A proof-of-concept phase Iia clinical trial to treat chronic HBV/HDV with the entry inhibitor myrcludex B. AASLD -Hepatology. 2016;64:abstract 229,121A.
  • Vaillant A. Nucleic acid polymers: broad spectrum antiviral activity, antiviral mechanisms and optimization for the treatment of hepatitis B and hepatitis D infection. Antiviral Res. 2016;133:32–40.
  • Foster WK, Miller DS, Marion PL, et al. Entecavir therapy combined with DNA vaccination for persistent duck hepatitis B virus infection. Antimicrob Agents Chemother. 2003;47:2624–2635.
  • Bazinet M, Pantea V, Cebotarescu V, et al. Follow up results from the REP 301 protocol: REP 2139-Ca and peg-IFN treatment in patients with chronic HBV/HDV infection. Hepatology. 2016;64:Abstract 1848, 912A.
  • Yurdaydin C, Idilman R, Keskin O, et al. A phase 2 dose-optimization study of lonafarnib with ritonavir for the treatment of chronic delta hepatitis—end of treatment results from the LOWR HDV-2 study. J Hepatol. 2017;66(suppl –1):s 33.
  • Ponzetto A, Hoyer BH, Popper H, et al. Titration of the infectivity of hepatitis D virus in chimpanzees. J Infect Dis. 1987;155:72–78.
  • Triantos C, Kalafateli M, Nikolopoulou V, et al. Meta-analysis: antiviral treatment for hepatitis D. Aliment Pharmacol Ther. 2012;35:663–673.
  • Ouzan D, Pénaranda G, Joly H, et al. Optimized HBsAg titer monitoring improves interferon therapy in patients with chronic delta. J Hepatol. 2013;58:1258–1259.
  • Niro GA, Smedile A, Fontana R, et al. HBsAg kinetics in chronic hepatitis D during interferon therapy. On-treatment prediction of response. Aliment Pharmacol Ther. 2016;44:620–628.
  • Singh S 1, Gupta SK, Nischal A, et al. Design of potential siRNA molecules for hepatitis delta virus gene silencing. Bioinformation. 2012;8:749–757.
  • Roger J, A H C, Von Ahsen U, et al. Inhibition of the self-cleavage reaction of the human hepatitis delta virus ribozyme by antibiotics. J Mol Biol. 1996;259:916–925.
  • Stokowa-Sołtys K, Gaggelli N, Nagaj J, et al. High affinity of copper(II) towards amoxicillin, apramycin and ristomycin. Effect of these complexes on the catalytic activity of HDV ribozyme. J Inorg Biochem. 2013;124:26–34.
  • Buchmann B, Döhner K, Schirdewahn T, et al. A screening assay for the identification of host cell requirements and antiviral targets for hepatitis D virus infection. Antiviral Res. 2017;141:116–123.
  • Grabowskj J, Wedemeyer H. Hepatitis delta;immunopathogenesis and clinical challenges. Dig Dis. 2010;28:133–138.
  • Huang YH, Wu JC, Hsu SC, et al. Varied immunity generated in mice by DNA vaccines with large and small hepatitis delta antigens. J Virol. 2003;77:12980–12985.
  • Fiedler M, Kosinska A, Schumann A, et al. Prime/boost immunization with DNA and adenoviral vectors protects from hepatitis D virus (HDV) infection after simultaneous infection with HDV and woodchuck hepatitis virus. J Virol. 2013;87:7708–7716.
  • Giersch K, Allweiss L, Volz T, et al. Hepatitis delta co-infection in humanized mice leads to pronounced induction of innate immune responses in comparison to HBV mono-infection. J Hepatol. 2015;63:346–353.

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