Top

Published in:

01-08-2015 | Clinical Review

Future therapy for hepatitis B virus infection

Author: Masahito Minami

Published in: Clinical Journal of Gastroenterology | Issue 4/2015

Abstract

We can now control hepatitis B virus infection by continuously administering nucleoside and nucleotide analogues such as entecavir and tenofovir. These drugs are generally safe and sufficiently effective, but future drugs are needed that can show off-treatment efficacy—in other words, eradication of latent hepatitis B virus DNA (covalently closed circular DNA) in the hepatocytes. This article is an overview of new drugs under development and some novel strategies to inhibit hepatitis B virus proliferation.

Liaw YF, Leung NW, Chang TT, Guan R, Tai DI, Ng KY, et al. Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Gastroenterology. 2000;119:172–80.CrossRefPubMed

Yao GB, Cui ZY, Wang BE, Yao JL, Zeng MD. A 3-year clinical trial of lamivudine in treatment of patients with chronic hepatitis B. Hepatobiliary Pancreat Dis Int. 2004;3:188–93.PubMed

Chang TT, Lai CL, Chien RN, Guan R, Lim SG, Lee CM, et al. Four years of lamivudine treatment in Chinese patients with chronic hepatitis B. J Gastroenterol Hepatol. 2004;19:1276–82.CrossRefPubMed

Lok AS, Lai CL, Leung N, Yao GB, Cui ZY, Schiff ER, et al. Long-term safety of lamivudine treatment in patients with chronic hepatitis B. Gastroenterology. 2003;125:1714–22.CrossRefPubMed

Fontana RJ. Side effects of long-term oral antiviral therapy for hepatitis B. Hepatology. 2009;49:S185–95.CrossRefPubMed

Seok JI, Lee DK, Lee CH, Park MS, Kim SY, Kim HS, et al. Long-term therapy with clevudine for chronic hepatitis B can be associated with myopathy characterized by depletion of mito- chondrial DNA. Hepatology. 2009;49:2080–6.CrossRefPubMed

van Nunen AB, Hansen BE, Suh DJ, Lohr HF, Chemello L, Fontaine H, et al. Durability of HBeAg seroconversion following antiviral therapy for chronic hepatitis B: relation to type of therapy and pretreatment serum hepatitis B virus DNA and ala- nine aminotransferase. Gut. 2003;52:420–4.PubMedCentralCrossRefPubMed

European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol. 2009;50:227–42.CrossRef

Ganem D, Prince AM. Hepatitis B virus infection—natural history and clinical consequences. N Engl J Med. 2004;350:1118–29.CrossRefPubMed

10.

Lok ASF, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50:661–2.CrossRefPubMed

11.

Lempp FA, Urban S. Inhibitors of hepatitis B virus attachment and entry. Intervirology 2014;57:151–7.

12.

Petersen J, Dandri M, Mier W, Lutgehetmann M, Volz T, von Weizsacker F, 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

13.

Ni Y, Lempp FA, Mehrle S, Nkongolo S, Kaufman C, Falth M, et al. Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species-specific entry into hepatocytes. Gastroenterology. 2014;146:1070–83.CrossRefPubMed

14.

Watashi K, Urban S, Li W, Wakita T. NTCP and beyond: opening the door to unveil hepatitis B virus entry. Int J Mol Sci. 2014;15:2892–905.PubMedCentralCrossRefPubMed

15.

Gallay P, Chatterji U, Bobardt M, Ure D, Trepanier D, Foster R, et al. Novel cyclophilin inhibitor CPI-431-32 shows broad spectrum antiviral activity by blocking replication of HCV, HBV, and HIV-1 viruses. J Hepatol. 2015;62:S677 (Abstract P0890).CrossRef

16.

Noordeen F, Vaillant A, Jilbert AR. Nucleic acid polymers prevent the establishment of duck hepatitis B virus infection in vivo. Antimicrob Agents Chemother. 2013;57:5291–8.PubMedCentralCrossRefPubMed

17.

Bazinet M, Pantea V, Cebotarescu V, Cojuhari L, Jimbei P, Vaillant A, et al. Significant reduction of HBsAg and HDV RNA by the nucleic acid polymer REP 2139 in Caucasian patients with chronic HBV/HDV co-infection. J Hepatol. 2015;62:S257–8 (Abstract LO2).CrossRef

18.

Jansen L, Vaillant A, Stelma F, Kootstra NA, Bazinet M, Al-Mahtabet M, et al. Serum HBV-RNA levels decline significantly in chronic hepatitis B patients dosed with the nucleic-acid polymer REP 2139-Ca. J Hepatol. 2015;62:S250 (Abstract O114).CrossRef

19.

Deres K, Schroder CH, Paessens A, Goldmann S, Hacker HJ, Weber O, et al. Inhibition of hepatitis B virus replication by drug-induced depletion of nucleocasids. Science. 2003;299:893–6.CrossRefPubMed

20.

Wu G, Liu B, Li J, Arzumanyan A, Clayton MM, Schinazi RF, et al. Preclinical characterization of GLS4, an inhibitor of hepatitis B virus core particle assembly. Antimicrob Agents Chemother. 2013;57:5344–54.PubMedCentralCrossRefPubMed

21.

Klumpp K, Shimada T, Allweiss L, Volz T, Luetgehetman M, Flores O, et al. High antiviral activitiy of the HBV core inhibitor NVR 3-778 in the humanized UPA/SCID mouse model. J Hepatol. 2015;62:S250 (Abstract O115).CrossRef

22.

Korolowicz K, Czerwinski S, Iyer R, Skell J, Yang J, Tucker R, et al. Antiviral efficacy and induction of host immune responses with SB9200, an oral prodrug of the dinucleotide SB 9000, in the woodchuck model of chronic hepatitis B (HBV) infection. J Hepatol. 2015;62:S557 (Abstract P0636).CrossRef

23.

Benetatos CA, Mitsuuchi Y, Burns JM, Meiman EM, Condon SM, Yu G, et al. Birinapant (TL32711), a bivalent SMAC mimetic, targets TRAF2-associated cIAPs, abrogates TNF-induced NF-κB activation, and is active in patient-derived xenograft models. Mol Cancer Ther. 2014;13:867–79.CrossRefPubMed

24.

Lanford RE, Guerra B, Chavez D, Giavedoni L, Hodara VL, Brasky KM, et al. GS-9620, an oral agonist of toll-like receptor-7, induces prolonged suppression of hepatitis B virus in chronically infected chimpanzees. Gastroenterology. 2013;144:1508–17.PubMedCentralCrossRefPubMed

25.

Gane EJ, Lim YS, Gordon SC, Visvanathan K, Sicard E, Fedorak RN et al. The oral toll-like receptor-7 agonist GS-9620 in patients with chronic hepatitis B virus infection. J Hepatol. 2015;63:320–8.CrossRefPubMed

26.

Perales MA, Goldberg JD, Yuan J, Koehne G, Lechner L, Papadopoulos EB, et al. Recombinat human interleukin-7 (cyt107) promotes T-cell recovery after allogeneic stem cell transplantation. Blood. 2012;120:4882–91.PubMedCentralCrossRefPubMed

27.

Mackall CL, Fry TJ, Ronald E, Gress RE. Harnessing the biology of IL-7 for therapeutic application. Nat Rev Immunol. 2011;11:330–42.CrossRefPubMed

28.

Gaggar A, Coeshott C, Apelian D, Rodell T, Brain R, Armstrong BR, Shen G, et al. Safety, tolerability and immunogenicity of GS-4774, a hepatitis Bvirus-specific therapeutic vaccine, in healthy subjects: a randomized study. Vaccine. 2014;32:4925–31.CrossRefPubMed

29.

Martin P, Dubois C, Jacquier E, Dion S, Mancini-Bourgine M, Godon O et al. TG1050, an immunotherapeutic to treat chronic hepatitis B, induces robust T cells and exerts an antiviral effect in HBV-persistent mice. Gut 2014 (epub ahead of print).

30.

Lelu K, Evlachev A, Kratzer R, Dion S, Mancini-Bourgine M, Godon O, et al. TG1050, a novel immunotherapeutic to treat chronic hepatitis B can control HBsAg and provoke HBsAg seroconversion in HBV-persistent mouse models. J Hepatol. 2015;62:S205 (Abstract O031).CrossRef

31.

Sebestyén MG, Wong SC, Trubetskoy V, Lewis DL, Wooddell CI. Targeted in vivo delivery of siRNA and an endosome-releasing agent to hepatocytes. Methods Mol Biol. 2015;1218:163–86.CrossRefPubMed

32.

Keeffe EM, Rossignol JF. Treatment of chronic viral hepatitis with nitazoxanide and second generation thiazolides. World J Gastroenterol. 2009;15:1805–8.PubMedCentralCrossRefPubMed

33.

Lucifora J, Xia Y, Reisinger F, Zhang K, Stadler D, Cheng X, et al. Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA. Science. 2014;343:1221–8.CrossRefPubMed

34.

Richman DD. The impact of drug resistance on the effectiveness of chemotherapy for chronic hepatitis B. Hepatology 2000; 32:866–7.

35.

Sarrazin C, Kieffer TL, Bartels D, Hanzelka B, Müh U, Welker M, et al. Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology. 2007;132:1767–77.CrossRefPubMed

36.

Suzuki Y, Ikeda K, Suzuki F, Toyota J, Karino Y, Chayama K, et al. Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment options. J Hepatol. 2013;58:655–62.CrossRefPubMed

Title: Future therapy for hepatitis B virus infection
Author: Masahito Minami
Publication date: 01-08-2015
Publisher: Springer Japan
Published in: Clinical Journal of Gastroenterology / Issue 4/2015
Print ISSN: 1865-7257
Electronic ISSN: 1865-7265
DOI: https://doi.org/10.1007/s12328-015-0590-y

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

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

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2015

Erratum to: Intestinal necrosis due to norovirus enteritis

EUS-FNA can be an effective procedure for the transesophageal drainage of a patient with intra-peritoneal abscess

A case of a teenage boy with eosinophilic gastroenteritis with esophageal involvement developing a hemorrhagic duodenal ulcer

Case report of chylous ascites with strangulated ileus and review of the literature

A case of a stomach gastrointestinal stromal tumor with extremely predominant cystic formation

Submucosal tumor-like lesion originating from colon tuberculosis: a case report and review of the literature

Keynote webinar | Spotlight on medication adherence

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

At a glance: The STEP trials