Skip to main content
Top
Published in: Current Hepatology Reports 4/2016

01-12-2016 | Hepatitis B (JK Lim, Section Editor)

Future Therapy for HBV: Role of Cell Cycle Inhibitors

Authors: Mayur Brahmania, Harry L. A. Janssen

Published in: Current Hepatology Reports | Issue 4/2016

Login to get access

Abstract

Despite the discovery of an effective vaccine over 30 years ago, hepatitis B virus (HBV) infection remains a significant cause of global mortality and morbidity affecting over 250 million individuals. Fortunately, many new antiviral agents targeting different steps of the HBV lifecycle are currently being developed marking a true shift in the treatment paradigm. It is hopeful these new therapies will provide a functional and durable cure from HBV infection from a finite duration of treatment.
Literature
1.
go back to reference Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 2006;45:529–38.CrossRefPubMed Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 2006;45:529–38.CrossRefPubMed
2.•
go back to reference Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386:1546–55. New World Health Organization estimates on the global prevalence of chronic Hepatitis B infection.CrossRefPubMed Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386:1546–55. New World Health Organization estimates on the global prevalence of chronic Hepatitis B infection.CrossRefPubMed
3.•
go back to reference Terrault NA, Bzowej NH, Chang K-M, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261–83. Latest guidelines on the diagnosis and management of chronic hepatitis B infection.CrossRefPubMed Terrault NA, Bzowej NH, Chang K-M, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261–83. Latest guidelines on the diagnosis and management of chronic hepatitis B infection.CrossRefPubMed
4.
go back to reference Papatheodoridis G, Buti M, Cornberg M, the European Association For The Study Of The Liver, et al. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167–85.CrossRef Papatheodoridis G, Buti M, Cornberg M, the European Association For The Study Of The Liver, et al. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol. 2012;57:167–85.CrossRef
5.
go back to reference Liaw YF, Kao JH, Piratvisuth T, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int. 2012;6:531–61.CrossRefPubMed Liaw YF, Kao JH, Piratvisuth T, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2012 update. Hepatol Int. 2012;6:531–61.CrossRefPubMed
6.
go back to reference Ahn J, Lee HM, Lim JK, Pan CQ, Nguyen MH, Ray Kim W, et al. Entecavir safety and effectiveness in a national cohort of treatment-naïve chronic hepatitis B patients in the US—the ENUMERATE study. Aliment Pharmacol Ther. 2016;43:134–44.CrossRefPubMed Ahn J, Lee HM, Lim JK, Pan CQ, Nguyen MH, Ray Kim W, et al. Entecavir safety and effectiveness in a national cohort of treatment-naïve chronic hepatitis B patients in the US—the ENUMERATE study. Aliment Pharmacol Ther. 2016;43:134–44.CrossRefPubMed
7.
go back to reference Marcellin P, Gane EJ, Flisiak R, et al. Long term treatment with tenofovir disoproxil fumarate for chronic hepatitis B infection is safe and well tolerated and associated with durable virologic response with no detectable resistance: 8 year results from two phase 3 trials. Boston: 65th Annual Meeting of the American Association for the Study of Liver Diseases; 2014. Marcellin P, Gane EJ, Flisiak R, et al. Long term treatment with tenofovir disoproxil fumarate for chronic hepatitis B infection is safe and well tolerated and associated with durable virologic response with no detectable resistance: 8 year results from two phase 3 trials. Boston: 65th Annual Meeting of the American Association for the Study of Liver Diseases; 2014.
8.
go back to reference Agarwal K, Fung SK, Nguyen TT, et al. Twenty-eight day safety, antiviral activity, and pharmacokinetics of tenofovir alafenamide for treatment of chronic hepatitis B infection. J Hepatol. 2015;62:533–40.CrossRefPubMed Agarwal K, Fung SK, Nguyen TT, et al. Twenty-eight day safety, antiviral activity, and pharmacokinetics of tenofovir alafenamide for treatment of chronic hepatitis B infection. J Hepatol. 2015;62:533–40.CrossRefPubMed
9.
go back to reference Lai CL, Wong D, Ip P, et al. Profound reduction of HBV covalently closed circular DNA with long-term nucleoside/tide analogue therapy. Boston: 65th Annual Meeting of the American Association for the Study of Liver Diseases; 2014. Lai CL, Wong D, Ip P, et al. Profound reduction of HBV covalently closed circular DNA with long-term nucleoside/tide analogue therapy. Boston: 65th Annual Meeting of the American Association for the Study of Liver Diseases; 2014.
10.
go back to reference Locarnini SA, Yuen L. Molecular genesis of drug-resistant and vaccine-escape HBV mutants. Antivir Ther. 2010;15:451–61.CrossRefPubMed Locarnini SA, Yuen L. Molecular genesis of drug-resistant and vaccine-escape HBV mutants. Antivir Ther. 2010;15:451–61.CrossRefPubMed
11.
go back to reference Lau GK, Piratvisuth T, Luo KX, and the Peginterferon Alfa-2a HBeAg-Positive Chronic Hepatitis B Study Group, et al. Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med. 2005;352:2682–95.CrossRefPubMed Lau GK, Piratvisuth T, Luo KX, and the Peginterferon Alfa-2a HBeAg-Positive Chronic Hepatitis B Study Group, et al. Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med. 2005;352:2682–95.CrossRefPubMed
12.
go back to reference Marcellin P, Lau GK, Bonino F, and the Peginterferon Alfa-2a HBeAg-Negative Chronic Hepatitis B Study Group, et al. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2004;351:1206–17.CrossRefPubMed Marcellin P, Lau GK, Bonino F, and the Peginterferon Alfa-2a HBeAg-Negative Chronic Hepatitis B Study Group, et al. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2004;351:1206–17.CrossRefPubMed
13.
go back to reference Buster EH, Flink HJ, Cakaloglu Y, et al. Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b. Gastroenterology. 2008;135:459–67.CrossRefPubMed Buster EH, Flink HJ, Cakaloglu Y, et al. Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b. Gastroenterology. 2008;135:459–67.CrossRefPubMed
14.
go back to reference van Zonneveld M, Honkoop P, Hansen BE, et al. Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B. Hepatology. 2004;39:804–10.CrossRefPubMed van Zonneveld M, Honkoop P, Hansen BE, et al. Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B. Hepatology. 2004;39:804–10.CrossRefPubMed
15.
go back to reference Janssen HL, van Zonneveld M, Senturk H, and the HBV 99-01 Study Group, the Rotterdam Foundation for Liver Research, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomized trial. Lancet. 2005;365:123–9.CrossRefPubMed Janssen HL, van Zonneveld M, Senturk H, and the HBV 99-01 Study Group, the Rotterdam Foundation for Liver Research, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomized trial. Lancet. 2005;365:123–9.CrossRefPubMed
16.
go back to reference Ning Q, Han M, Sun Y, et al. Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial). J Hepatol. 2014;61:777–84.CrossRefPubMed Ning Q, Han M, Sun Y, et al. Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial). J Hepatol. 2014;61:777–84.CrossRefPubMed
17.
go back to reference Shi M, Wang RS, Zhang H, et al. Sequential treatment with lamivudine and interferon-alpha monotherapies in hepatitis B e antigen-negative Chinese patients and its suppression of lamivudine-resistant mutations. J Antimicrob Chemother. 2006;58:1031–5.CrossRefPubMed Shi M, Wang RS, Zhang H, et al. Sequential treatment with lamivudine and interferon-alpha monotherapies in hepatitis B e antigen-negative Chinese patients and its suppression of lamivudine-resistant mutations. J Antimicrob Chemother. 2006;58:1031–5.CrossRefPubMed
18.
go back to reference Chan HL, Leung NW, Hui AY, et al. A randomized, controlled trial of combination therapy for chronic hepatitis B: comparing pegylated interferon-alpha2b and lamivudine with lamivudine alone. Ann Intern Med. 2005;142:240–50.CrossRefPubMed Chan HL, Leung NW, Hui AY, et al. A randomized, controlled trial of combination therapy for chronic hepatitis B: comparing pegylated interferon-alpha2b and lamivudine with lamivudine alone. Ann Intern Med. 2005;142:240–50.CrossRefPubMed
19.
go back to reference Brouwer WP, Xie Q, Sonneveld MJ, et al. Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: a multicenter randomized trial (ARES study). Hepatology. 2015;61:1512–22.CrossRefPubMed Brouwer WP, Xie Q, Sonneveld MJ, et al. Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: a multicenter randomized trial (ARES study). Hepatology. 2015;61:1512–22.CrossRefPubMed
20.
go back to reference Urban S, Bartenschlager R, Kubitz R, Zoulim F. Strategies to inhibit entry of HBV and HDV into hepatocytes. Gastroenterology. 2014;147:48–64.CrossRefPubMed Urban S, Bartenschlager R, Kubitz R, Zoulim F. Strategies to inhibit entry of HBV and HDV into hepatocytes. Gastroenterology. 2014;147:48–64.CrossRefPubMed
21.
go back to reference Claro da Silva T, Polli JE, Swaan PW. The solute carrier family 10 (SLC10): beyond bile acid transport. Mol Aspects Med. 2013;34:252–69.CrossRefPubMed Claro da Silva T, Polli JE, Swaan PW. The solute carrier family 10 (SLC10): beyond bile acid transport. Mol Aspects Med. 2013;34:252–69.CrossRefPubMed
22.
go back to reference Eloranta JJ, Jung D, Kullak-Ublick GA. The human Na+-taurocholate cotransporting polypeptide gene is activated by glucocorticoid receptor and peroxisome proliferator-activated receptor-gamma coactivator-1alpha, and suppressed by bile acids via a small heterodimer partner-dependent mechanism. Mol Endocrinol. 2006;20:65–79.CrossRefPubMed Eloranta JJ, Jung D, Kullak-Ublick GA. The human Na+-taurocholate cotransporting polypeptide gene is activated by glucocorticoid receptor and peroxisome proliferator-activated receptor-gamma coactivator-1alpha, and suppressed by bile acids via a small heterodimer partner-dependent mechanism. Mol Endocrinol. 2006;20:65–79.CrossRefPubMed
23.
go back to reference 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;79:1613–22.CrossRefPubMedPubMedCentral 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;79:1613–22.CrossRefPubMedPubMedCentral
24.
go back to reference Schulze A, Schieck A, Ni Y, Mier W, Urban S. Fine mapping of pre-S sequence requirements for hepatitis B virus large envelope protein-mediated receptor interaction. J Virol. 2010;84:1989–2000.CrossRefPubMed Schulze A, Schieck A, Ni Y, Mier W, Urban S. Fine mapping of pre-S sequence requirements for hepatitis B virus large envelope protein-mediated receptor interaction. J Virol. 2010;84:1989–2000.CrossRefPubMed
25.
go back to reference Petersen J, Dandri M, Mier W, et al. Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein. Nat Biotechnol. 2008;26:335–41.CrossRefPubMed Petersen J, Dandri M, Mier W, et al. Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein. Nat Biotechnol. 2008;26:335–41.CrossRefPubMed
26.•
go back to reference Volz T, Allweiss L, Ben MBarek M, et al. The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus. J Hepatol. 2013;58:861–7. First study showing the effectiveness of Myrcludex B inactivating the NTCP receptor and preventing new hepatitis B infection.CrossRefPubMed Volz T, Allweiss L, Ben MBarek M, et al. The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus. J Hepatol. 2013;58:861–7. First study showing the effectiveness of Myrcludex B inactivating the NTCP receptor and preventing new hepatitis B infection.CrossRefPubMed
27.
go back to reference Watashi K, Sluder A, Daito T, Matsunaga S, Ryo A, Nagamori S, et al. Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter NTCP. Hepatology. 2014;59:1726–37.CrossRefPubMedPubMedCentral Watashi K, Sluder A, Daito T, Matsunaga S, Ryo A, Nagamori S, et al. Cyclosporin A and its analogs inhibit hepatitis B virus entry into cultured hepatocytes through targeting a membrane transporter NTCP. Hepatology. 2014;59:1726–37.CrossRefPubMedPubMedCentral
28.
go back to reference Nkongolo S, Ni Y, 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;60:723–31.CrossRefPubMed Nkongolo S, Ni Y, 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;60:723–31.CrossRefPubMed
29.
go back to reference Zimmerman KA, Fischer KP, Joyce MA, Tyrrell DL. Zinc finger proteins designed to specifically target duck hepatitis B virus covalently closed circular DNA inhibit viral transcription in tissue culture. J Virol. 2008;82:8013–21.CrossRefPubMedPubMedCentral Zimmerman KA, Fischer KP, Joyce MA, Tyrrell DL. Zinc finger proteins designed to specifically target duck hepatitis B virus covalently closed circular DNA inhibit viral transcription in tissue culture. J Virol. 2008;82:8013–21.CrossRefPubMedPubMedCentral
30.
go back to reference Chen J, Zhang W, Lin J, et al. An efficient antiviral strategy for targeting hepatitis B virus genome using transcription activator-like effector nucleases. Mol Ther. 2014;22(2):303–11.CrossRefPubMed Chen J, Zhang W, Lin J, et al. An efficient antiviral strategy for targeting hepatitis B virus genome using transcription activator-like effector nucleases. Mol Ther. 2014;22(2):303–11.CrossRefPubMed
31.•
go back to reference Horvath P, Barrangou R. CRISPR/Cas, the immune system of bacteria and archaea. Science. 2010;327:167–70. A concise overview of the CRISPR system.CrossRefPubMed Horvath P, Barrangou R. CRISPR/Cas, the immune system of bacteria and archaea. Science. 2010;327:167–70. A concise overview of the CRISPR system.CrossRefPubMed
33.
go back to reference Dong C, Qu L, Wang H, Wei L, Dong Y, Xiong S. Targeting hepatitis B virus cccDNA by CRISPR/Cas9 nuclease efficiently inhibits viral replication. Antiviral Res. 2015;118:110–7.CrossRefPubMed Dong C, Qu L, Wang H, Wei L, Dong Y, Xiong S. Targeting hepatitis B virus cccDNA by CRISPR/Cas9 nuclease efficiently inhibits viral replication. Antiviral Res. 2015;118:110–7.CrossRefPubMed
34.
go back to reference Liu X, Hao R, Chen S, Guo D, Chen Y. Inhibition of hepatitis B virus by CRISPR/Cas9 system via targeting the conserved regions of the viral genome. J Gen Virol. 2015;96:2252–61.CrossRefPubMed Liu X, Hao R, Chen S, Guo D, Chen Y. Inhibition of hepatitis B virus by CRISPR/Cas9 system via targeting the conserved regions of the viral genome. J Gen Virol. 2015;96:2252–61.CrossRefPubMed
35.
go back to reference Kennedy EM, Bassit LC, Mueller H, et al. Suppression of hepatitis B virus DNA accumulation in chronically infected cells using a bacterial CRISPR/Cas RNA-guided DNA endonuclease. Virology. 2015;476:196–205.CrossRefPubMed Kennedy EM, Bassit LC, Mueller H, et al. Suppression of hepatitis B virus DNA accumulation in chronically infected cells using a bacterial CRISPR/Cas RNA-guided DNA endonuclease. Virology. 2015;476:196–205.CrossRefPubMed
36.
go back to reference Belloni L, Allweiss L, Guerrieri F, et al. IFN-α inhibits HBV transcription and replication in cell culture and in humanized mice by targeting the epigenetic regulation of the nuclear cccDNA minichromosome. J Clin Invest. 2012;122:529–37.CrossRefPubMedPubMedCentral Belloni L, Allweiss L, Guerrieri F, et al. IFN-α inhibits HBV transcription and replication in cell culture and in humanized mice by targeting the epigenetic regulation of the nuclear cccDNA minichromosome. J Clin Invest. 2012;122:529–37.CrossRefPubMedPubMedCentral
38.
go back to reference Klein C, Bock CT, Wedemeyer H, et al. Inhibition of hepatitis B virus replication in vivo by nucleoside analogues and siRNA. Gastroenterology. 2003;125:9–18.CrossRefPubMed Klein C, Bock CT, Wedemeyer H, et al. Inhibition of hepatitis B virus replication in vivo by nucleoside analogues and siRNA. Gastroenterology. 2003;125:9–18.CrossRefPubMed
39.
go back to reference Shlomai A, Shaul Y. Inhibition of hepatitis B virus expression and replication by RNA interference. Hepatology. 2003;37:764–70.CrossRefPubMed Shlomai A, Shaul Y. Inhibition of hepatitis B virus expression and replication by RNA interference. Hepatology. 2003;37:764–70.CrossRefPubMed
40.
go back to reference Yuen M, Chan H, Liu K, et al. ARC-520 produces deep and durable knockdown of viral antigens and DNA in a phase II study in patients with chronic hepatitis B. San Francisco: 66th Annual Meeting of the American Association for the Study of Liver Diseases; 2015. Yuen M, Chan H, Liu K, et al. ARC-520 produces deep and durable knockdown of viral antigens and DNA in a phase II study in patients with chronic hepatitis B. San Francisco: 66th Annual Meeting of the American Association for the Study of Liver Diseases; 2015.
41.
go back to reference Gish RD, Yuen MF, Chan HL, et al. Synthetic RNAi triggers and their use in chronic hepatitis B therapies with curative intent. Antiviral Res 2015;121:97–108. Gish RD, Yuen MF, Chan HL, et al. Synthetic RNAi triggers and their use in chronic hepatitis B therapies with curative intent. Antiviral Res 2015;121:97–108.
42.
go back to reference Feld JJ, Colledge D, Sozzi V, Edwards R, Littlejohn M, Locarnini SA. The phenylpropenamide derivative AT-130 blocks HBV replication at the level of viral RNA packaging. Antiviral Res. 2007;76:168–77.CrossRefPubMed Feld JJ, Colledge D, Sozzi V, Edwards R, Littlejohn M, Locarnini SA. The phenylpropenamide derivative AT-130 blocks HBV replication at the level of viral RNA packaging. Antiviral Res. 2007;76:168–77.CrossRefPubMed
43.
go back to reference Deres K, Schroder CH, Paessens A, et al. Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids. Science. 2003;299:893–6.CrossRefPubMed Deres K, Schroder CH, Paessens A, et al. Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocapsids. Science. 2003;299:893–6.CrossRefPubMed
44.
go back to reference Stray SJ, Bourne CR, Punna S, Lewis WG, Finn MG, Zlotnick A. A heteroaryldihydropyrimidine activates and can misdirect hepatitis B virus capsid assembly. Proc Natl Acad Sci U S A. 2005;102:8138–43.CrossRefPubMedPubMedCentral Stray SJ, Bourne CR, Punna S, Lewis WG, Finn MG, Zlotnick A. A heteroaryldihydropyrimidine activates and can misdirect hepatitis B virus capsid assembly. Proc Natl Acad Sci U S A. 2005;102:8138–43.CrossRefPubMedPubMedCentral
45.
go back to reference Wu GY, Zheng XJ, Yin CC, et al. Inhibition of hepatitis B virus replication by Bay 41-4109 and its association with nucleocapsid disassembly. J Chemother. 2008;20:458–67.CrossRefPubMed Wu GY, Zheng XJ, Yin CC, et al. Inhibition of hepatitis B virus replication by Bay 41-4109 and its association with nucleocapsid disassembly. J Chemother. 2008;20:458–67.CrossRefPubMed
46.
go back to reference Delaney 4th WE, Edwards R, Colledge D, et al. Phenylpropenamide derivatives AT-61 and AT-130 inhibit replication of wild-type and lamivudine-resistant strains of hepatitis B virus in vitro. Antimicrob Agents Chemother. 2002;46:3057–60.CrossRefPubMed Delaney 4th WE, Edwards R, Colledge D, et al. Phenylpropenamide derivatives AT-61 and AT-130 inhibit replication of wild-type and lamivudine-resistant strains of hepatitis B virus in vitro. Antimicrob Agents Chemother. 2002;46:3057–60.CrossRefPubMed
47.
go back to reference Liaw S, Brown N, Klumpp K, et al. Phase 1b efficacy and safely of NVR 3-778, a first-in-class HBV core inhibitor, in HBeAg-positive patients with chronic HBV infection. San Francisco: 66th Annual Meeting of the American Association for the Study of Liver Diseases; 2015. Liaw S, Brown N, Klumpp K, et al. Phase 1b efficacy and safely of NVR 3-778, a first-in-class HBV core inhibitor, in HBeAg-positive patients with chronic HBV infection. San Francisco: 66th Annual Meeting of the American Association for the Study of Liver Diseases; 2015.
48.
go back to reference Bertoletti A, Ferrari C. Innate and adaptive immune responses in chronic hepatitis B virus infections: towards restoration of immune control of viral infection. Gut. 2012;61:1754–64.CrossRefPubMed Bertoletti A, Ferrari C. Innate and adaptive immune responses in chronic hepatitis B virus infections: towards restoration of immune control of viral infection. Gut. 2012;61:1754–64.CrossRefPubMed
49.
go back to reference Korba BE, Montero AB, Farrar K, et al. Nitazoxanide, tizoxanide and other thiazolides are potent inhibitors of hepatitis B virus and hepatitis C virus replication. Antiviral Res. 2008;77:56–63.CrossRefPubMed Korba BE, Montero AB, Farrar K, et al. Nitazoxanide, tizoxanide and other thiazolides are potent inhibitors of hepatitis B virus and hepatitis C virus replication. Antiviral Res. 2008;77:56–63.CrossRefPubMed
50.
go back to reference Dougherty AM, Guo H, Westby G, et al. A substituted tetrahydro-tetrazolo-pyrimidine is a specific and novel inhibitor of hepatitis B virus surface antigen secretion. Antimicrob Agents Chemother. 2007;51:4427–37.CrossRefPubMedPubMedCentral Dougherty AM, Guo H, Westby G, et al. A substituted tetrahydro-tetrazolo-pyrimidine is a specific and novel inhibitor of hepatitis B virus surface antigen secretion. Antimicrob Agents Chemother. 2007;51:4427–37.CrossRefPubMedPubMedCentral
51.
go back to reference Yu W, Goddard C, Clearfield E, et al. Design, synthesis, and biological evaluation of triazolo-pyrimidine derivatives as novel inhibitors of hepatitis B virus surface antigen (HBsAg) secretion. J Med Chem. 2011;54:5660–70.CrossRefPubMedPubMedCentral Yu W, Goddard C, Clearfield E, et al. Design, synthesis, and biological evaluation of triazolo-pyrimidine derivatives as novel inhibitors of hepatitis B virus surface antigen (HBsAg) secretion. J Med Chem. 2011;54:5660–70.CrossRefPubMedPubMedCentral
53.
go back to reference Siegler VD, Bruss V. Role of transmembrane domains of hepatitis B virus small surface proteins in subviral-particle biogenesis. J Virol. 2013;87:1491–6.CrossRefPubMedPubMedCentral Siegler VD, Bruss V. Role of transmembrane domains of hepatitis B virus small surface proteins in subviral-particle biogenesis. J Virol. 2013;87:1491–6.CrossRefPubMedPubMedCentral
54.
go back to reference Jansen L, Vaillant A, van Dort K, et al. Serum HBV-RNA levels decline significantly in chronic hepatitis B patients dosed with the nucleic-acid polymer REP 2139-Ca. Vienna: 2015 International Liver Congress: 50th Annual Meeting of the European Association for the Study of the Liver (EASL); 2015. Jansen L, Vaillant A, van Dort K, et al. Serum HBV-RNA levels decline significantly in chronic hepatitis B patients dosed with the nucleic-acid polymer REP 2139-Ca. Vienna: 2015 International Liver Congress: 50th Annual Meeting of the European Association for the Study of the Liver (EASL); 2015.
55.
go back to reference Hopkins S, DiMassimo B, Rusnak P, et al. The cyclophilin inhibitor SCY-635 suppresses viral replication and induces endogenous interferons in patients with chronic HCV genotype 1 infection. J Hepatol. 2012;57:47–54.CrossRefPubMed Hopkins S, DiMassimo B, Rusnak P, et al. The cyclophilin inhibitor SCY-635 suppresses viral replication and induces endogenous interferons in patients with chronic HCV genotype 1 infection. J Hepatol. 2012;57:47–54.CrossRefPubMed
56.
go back to reference Hopkins S, Bobardt M, Chatterji U, Garcia-Rivera JA, Lim P, Gallay PA. The cyclophilin inhibitor SCY-635 disrupts hepatitis C virus NS5A-cyclophilin A complexes. Antimicrob Agents Chemother. 2012;56:3888–97.CrossRefPubMedPubMedCentral Hopkins S, Bobardt M, Chatterji U, Garcia-Rivera JA, Lim P, Gallay PA. The cyclophilin inhibitor SCY-635 disrupts hepatitis C virus NS5A-cyclophilin A complexes. Antimicrob Agents Chemother. 2012;56:3888–97.CrossRefPubMedPubMedCentral
57.
go back to reference Phillips S, Chokshi S, Chatterji U, et al. Alisporivir inhibition of hepatocyte cyclophilins reduces HBV replication and hepatitis B surface antigen production. Gastroenterology. 2015;148:403–14.CrossRefPubMed Phillips S, Chokshi S, Chatterji U, et al. Alisporivir inhibition of hepatocyte cyclophilins reduces HBV replication and hepatitis B surface antigen production. Gastroenterology. 2015;148:403–14.CrossRefPubMed
Metadata
Title
Future Therapy for HBV: Role of Cell Cycle Inhibitors
Authors
Mayur Brahmania
Harry L. A. Janssen
Publication date
01-12-2016
Publisher
Springer US
Published in
Current Hepatology Reports / Issue 4/2016
Electronic ISSN: 2195-9595
DOI
https://doi.org/10.1007/s11901-016-0313-y

Other articles of this Issue 4/2016

Current Hepatology Reports 4/2016 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.