Semin Liver Dis 2004; 24: 77-82
DOI: 10.1055/s-2004-828682
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

New Treatment of Chronic Hepatitis B

Anna S. F. Lok1
  • 1Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, Michigan
Further Information

Publication History

Publication Date:
11 June 2004 (online)

Currently approved treatments for chronic hepatitis B are limited by low rates of sustained response, side effects, or drug resistance. Thus, new treatments that have more potent antiviral effects, less toxicity, and minimal or no risk of resistance are needed. This article will focus on new antiviral agents that are being evaluated in clinical trials.

REFERENCES

  • 1 Seifer M, Hamatake R K, Colonno R J, Standring D N. In vitro inhibition of hepadnavirus polymerases by the triphosphates of BMS-200475 and lobucavir.  Antimicrob Agents Chemother. 1998;  42 3200-3208
  • 2 Ono S, Kato N, Shiratori Y et al.. The polymerase L528M mutation cooperates with nucleotide binding-site mutations, increasing hepatitis B virus replication and drug resistance.  J Clin Invest. 2001;  107 449-455
  • 3 Colonno R, Genovesi E, Medina I et al.. Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection.  J Infect Dis. 2001;  184 1236-1245
  • 4 Marion P, Salazar F, Winters M, Colonno R. Potent efficacy of entecavir (BMS-200475) in a duck model of hepatitis B virus replication.  Antimicrob Agents Chemother. 2002;  46 82-88
  • 5 Lai C L, Rosmawati M, Lao J et al.. Entecavir is superior to lamivudine in reducing hepatitis B virus DNA in patients with chronic hepatitis B infection.  Gastroenterology. 2002;  123 1831-1838
  • 6 Chang T, Hadziyannis S, Cianciara J et al.. Sustained viral load and ALT reduction following 48 weeks of entecavir treatment in subjects with chronic hepatitis B who have failed lamivudine.  Hepatology. 2002;  36 300A
  • 7 Shakil A, Lilly L, Angus P et al.. Entecavir significantly reduces viral load in liver transplant recipients failing lamivudine therapy for chronic hepatitis B infection.  J Hepatol. 2002;  36(Suppl 1) 122
  • 8 Le Guerhier F, Pichoud C, Guerret S et al.. Characterization of the antiviral effect of 2',3′-dideoxy-2', 3′-didehydro-beta-L-5-fluorocytidine in the duck hepatitis B virus infection model.  Antimicrob Agents Chemother. 2000;  44 111-122
  • 9 Gish R G, Leung N W, Wright T L et al.. Anti-hepatitis B virus (HBV) activity and pharmacokinetics of FTC in a 2 month trial in HBV infected patients.  Gastroenterology. 1999;  116 A1216
  • 10 Gish R, Leung N, Wang C et al.. Antiviral activity, safety, and incidence of resistance in chronically infected hepatitis B patients (CHB) given once daily emtricitabine for 2 years.  Hepatology. 2002;  36 372A
  • 11 Liaw Y F, Leung N W, Chang T T et al.. Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group.  Gastroenterology. 2000;  119 172-180
  • 12 Balakrishna Pai S, Liu S H, Zhu Y L, Chu C K, Cheng Y C. Inhibition of hepatitis B virus by a novel L-nucleoside, 2'-fluoro-5-methyl-beta-L-arabinofuranosyl uracil.  Antimicrob Agents Chemother. 1996;  40 380-386
  • 13 Peek S F, Cote P J, Jacob J R et al.. Antiviral activity of clevudine [L-FMAU, (1-(2-fluoro-5-methyl-β, L-arabinofuranosyl) uracil)] against woodchuck hepatitis virus replication and gene expression in chronically infected woodchucks (Marmota monax).  Hepatology. 2001;  33 254-266
  • 14 Marcellin P, Sacks S, Lau G KK et al.. A dose-escalating trial evaluating the safety and antiviral activity of clevudine in patients with chronic HBV infection.  Gastroenterology. 2003;  124 A709
  • 15 Bryant M, Bridges E, Placidi L et al.. Antiviral L-nucleosides specific for hepatitis B virus infection.  Antimicrob Agents Chemother. 2001;  45 229-235
  • 16 Tennant B, Meene S, Baldwin B et al.. Antiviral activities of beta-L-thymidine (LdT), val-beta-L-2'-deoxycytidine (val-LdC), and lamivudine alone and in combination in a 12 week, oral dose study using the woodchuck model of chronic hepatitis B virus infection. Antiviral Research. HEP DART 2001.  Frontiers in Drug Development for Viral Hepatitis. 2001;  32 A27
  • 17 Lai C, Lam P, Myers M et al.. Safe and potent suppression of hepatitis B virus (HBV) with L-deoxythymidine (LDT): results of a dose-escalation trial.  Hepatology. 2001;  34 321A
  • 18 Lai C, Leung N, Teo E K et al.. Results of a one-year international phase IIB comparative trial of telbivudine, lamivudine, and the combination, in patients with chronic hepatitis B.  Hepatology. 2003;  38 262A
  • 19 Lim S, Lai C, Dan Y et al.. Val-LdC: first evidence of efficacy and safety for a new anti-HBV agent.  Gastroenterology. 2002;  A628
  • 20 Lin T, Luo M, Liu M et al.. Design and synthesis of 2′,3′-dideoxy-2′,3′-didehydro-β-L-cytidine (β-L-d4C) and 2′,3′-dideoxy-2′,3′-didehydro-β-L-5-fluorocytidine (β-L-Fd4C), two exceptionally potent inhibitors of human hepatitis B virus (HBV) and potent inhibitors of human immunodeficiency virus (HIV) in vitro.  J Med Chem. 1996;  39 1757-1759
  • 21 Afdal N, O'Brien C, Oshana S, Dunkle L. Potent anti-HBV activity of ACH-126,443 correlated with 14-day pharmacokinetics and safety: predictions for activity against YMDD mutant strains.  Hepatology. 2002;  36 372A
  • 22 Ying C, De Clercq E, Nicholson W et al.. Inhibition of the replication of the DNA polymerase M550V mutation variant of human hepatitis B virus by adefovir, tenofovir, L-FMAU, DAPD, penciclovir and lobucavir.  J Viral Hepat. 2000;  7 161-165
  • 23 Benhamou Y, Tubiana R, Thibault V. Tenofovir disoproxil fumarate in patients with HIV and lamivudine-resistant hepatitis B virus.  N Engl J Med. 2003;  348 177-178
  • 24 van Bommel F, Wunsche T, Schurmann D, Berg T. Tenofovir treatment in patients with lamivudine-resistant hepatitis B mutants strongly affects viral replication.  Hepatology. 2002;  36 507-508
  • 25 Nelson M, Portsmouth S, Stebbing J et al.. An open-label study of tenofovir in HIV-1 and hepatitis B virus co-infected individuals.  AIDS. 2003;  17 F7-F10
  • 26 Nunez M, Perez-Olmeda M, Diaz B et al.. Activity of tenofovir on hepatitis B virus replication in HIV-co-infected patients failing or partially responding to lamivudine.  AIDS. 2002;  16 2352-2354
  • 27 Ristig M, Crippin J, Aberg J et al.. Tenofovir disoproxil fumarate therapy for chronic hepatitis B in human immunodeficiency virus/hepatitis B virus-coinfected individuals for whom interferon-α and lamivudine therapy have failed.  J Infect Dis. 2002;  186 1844-1847
  • 28 van Bommel F, Wunsche T, Schurmann D et al.. A comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus (HBV) infection.  Hepatology. 2003;  38 275A
  • 29 Schooley R, Ruane P, Myers R et al.. Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study.  AIDS. 2002;  16 1257-1263
  • 30 Verheist D, Monge M, Meynard J L et al.. Fanconi syndrome and renal failure induced by tenofovir: a first case report.  Am J Kidney Dis. 2002;  40 1331-1333

Anna S F LokM.D. 

Division of Gastroenterology, University of Michigan Medical Center

3912 Taubman Center, Box 0362, Ann Arbor, MI 48109

Email: aslok@umich.edu

    >