Abstract
Chronic hepatitis B and C affect approximately 500 million people in the world, with substantial disease burden including liver cirrhosis and hepatocellular carcinoma. For chronic hepatitis B, two treatment strategies are currently available, both with suboptimal response and significant side effects. Promising new drugs are approaching the stage of approval; however, these agents still need further development to control this disease. Based on the understanding of the hepatitis C virus life cycle, new treatment developments for chronic hepatitis C tend to succeed rapidly; therefore, it is only a matter of time before new therapies emerge. This review summarizes the most important new agents available for treatment of chronic hepatitis B and C.
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References and Recommended Reading
World Health Organization: The World Health Report 1997: Conquering Suffering, Enriching Humanity. Geneva, Switzerland: World Health Organization; 1997.
Perz JF, Armstrong GL, Farrington LA, et al.: The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 2006, 45:529–538.
Goldstein ST, Zhou F, Hadler SC, et al.: A mathematical model to estimate global hepatitis B disease burden and vaccination impact. Int J Epidemiol 2005, 34:1329–1339.
World Health Organization: Hepatitis B fact sheet No. 204. http://www.who.int/mediacentre/factsheets/fs204/en/print. html. Updated October 2000. Accessed October 30, 2007.
Hoofnagle JH, Doo E, Liang TJ, et al.: Management of hepatitis B: summary of a clinical research workshop. Hepatology 2007, 45:1056–1075.
Lok AS, McMahon BJ: Chronic hepatitis B. Hepatology 2007, 45:507–539.
de Franchis R, Meucci G, Vecchi M, et al.: The natural history of asymptomatic hepatitis B surface antigen carriers. Ann Intern Med 1993, 118:191–194.
Wong DK, Cheung AM, O’Rourke K, et al.: Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis. Ann Intern Med 1993, 119:312–323.
Schalm SW, Heathcote J, Cianciara J, et al.: Lamivudine and alpha interferon combination treatment of patients with chronic hepatitis B infection: a randomised trial. Gut 2000, 46:562–568.
Lau GK, Piratvisuth T, Luo KX, et al.: Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med 2005, 352:2682–2695.
Janssen HL, van Zonneveld M, Senturk H, et al.: Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet 2005, 365:123–129.
Dienstag JL, Schiff ER, Wright TL, et al.: Lamivudine as initial treatment for chronic hepatitis B in the United States. N Engl J Med 1999, 341:1256–1263.
Marcellin P, Chang TT, Lim SG, et al.: Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med 2003, 348:808–816.
Chang TT, Gish RG, de Man R, et al.: A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med 2006, 354:1001–1010.
Lai CL, Leung N, Teo EK, et al.: A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B. Gastroenterology 2005, 129:528–536
Marcellin P, Lau GK, Bonino F, 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, 351:1206–1217.
Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, et al.: Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B. N Engl J Med 2003, 348:800–807.
Lai CL, Shouval D, Lok AS, et al.: Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med 2006, 354:1011–1020.
Cooksley WG, Piratvisuth T, Lee SD, et al.: Peginterferon alpha-2a (40 kDa): an advance in the treatment of hepatitis B e antigen-positive chronic hepatitis B. J Viral Hepat 2003, 10:298–305.
Gish RG, Lau DT, Schmid P, Perrillo R: A pilot study of extended duration peginterferon alfa-2a for patients with hepatitis B e antigen-negative chronic hepatitis B. Am J Gastroenterol 2007, [Epub ahead of print].
Tassopoulos NC, Volpes R, Pastore G, et al.: Efficacy of lamivudine in patients with hepatitis B e antigen-negative/ hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B. Lamivudine Precore Mutant Study Group. Hepatology 1999, 29:889–896.
Sherman M, Yurdaydin C, Sollano J, et al.: Entecavir for treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B. Gastroenterology 2006, 130:2039–2049.
Peters MG, Hann HH, Martin P, et al.: Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B. Gastroenterology 2004, 126:91–101.
Rapti I, Dimou E, Mitsoula P, Hadziyannis SJ: Adding-on versus switching-to adefovir therapy in lamivudine-resistant HBeAg-negative chronic hepatitis B. Hepatology 2007, 45:307–313.
Dore GJ, Cooper DA, Pozniak AL, et al.: Efficacy of tenofovir disoproxil fumarate in antiretroviral therapy-naive and-experienced patients coinfected with HIV-1 and hepatitis B virus. J Infect Dis 2004, 189:1185–1192.
Peters MG, Andersen J, Lynch P, et al.: Randomized controlled study of tenofovir and adefovir in chronic hepatitis B virus and HIV infection: ACTG A5127. Hepatology 2006, 44:1110–1116.
van Bommel F, Zollner B, Sarrazin C, et al.: Tenofovir for patients with lamivudine-resistant hepatitis B virus (HBV) infection and high HBV DNA level during adefovir therapy. Hepatology 2006, 44:318–325.
van Bommel F, Wunsche T, Mauss S, et al.: Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection. Hepatology 2004, 40:1421–1425.
Lim SG, Ng TM, Kung N, et al.: A double-blind placebocontrolled study of emtricitabine in chronic hepatitis B. Arch Intern Med 2006, 166:49–56.
Yoo BC, Kim JH, Chung YH, et al.: Twenty-four-week clevudine therapy showed potent and sustained antiviral activity in HBeAg-positive chronic hepatitis B. Hepatology 2007, 45:1172–1178.
Yoo BC, Kim JH, Kim TH, et al.: Clevudine is highly efficacious in hepatitis B e antigen-negative chronic hepatitis B with durable off-therapy viral suppression. Hepatology 2007, 46:1041–1048.
Lin CC, Xu C, Teng A, et al.: Pharmacokinetics of pradefovir and PMEA in healthy volunteers after oral dosing of pradefovir. J Clin Pharmacol 2005, 45:1250–1258.
Lai CL, Brown NA, Myers M: Valtorcitabine provides potent suppression of hepatitis B virus in patients with chronic hepatitis: results of a phase I/II clinical trial. Hepatology 2004, 40:173A.
Fried MW, Shiffman ML, Reddy KR, et al.: Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002, 347:975–982.
Manns MP, McHutchison JG, Gordon SC, et al.: Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001, 358:958–965.
Lohmann V, Korner F, Koch J, et al.: Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 1999, 285:110–113.
Lindenbach BD, Evans MJ, Syder AJ, et al.: Complete replication of hepatitis C virus in cell culture. Science 2005, 309:623–626.
Pawlotsky JM: Current and future concepts in hepatitis C therapy. Semin Liver Dis 2005, 25:72–83.
Penin F: Structural biology of hepatitis C virus. Clin Liver Dis 2003, 7:1–21.
Hsu M, Zhang J, Flint M, et al.: Hepatitis C virus glycoproteins mediate pH-dependent cell entry of pseudotyped retroviral particles. Proc Natl Acad Sci U S A 2003, 100:7271–7276.
Perez-Berna AJ, Moreno MR, Guillen J, et al.: The membrane-active regions of the hepatitis C virus E1 and E2 envelope glycoproteins. Biochemistry 2006, 45:3755–3768.
Flint M, McKeating JA: The role of the hepatitis C virus glycoproteins in infection. Rev Med Virol 2000, 10:101–117.
Eren R, Landstein D, Terkieltaub D, et al.: Preclinical evaluation of two neutralizing human monoclonal antibodies against hepatitis C virus (HCV): a potential treatment to prevent HCV reinfection in liver transplant patients. J Virol 2006, 80:2654–2664.
Davis GL, Nelson DR, Terrault N, et al.: A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients. Liver Transpl 2005, 11:941–949.
Hanecak R, Brown-Driver V, Fox MC, et al.: Antisense oligonucleotide inhibition of hepatitis C virus gene expression in transformed hepatocytes. J Virol 1996, 70:5203–5212.
McHutchison JG, Patel K, Pockros P, et al.: A phase I trial of an antisense inhibitor of hepatitis C virus (ISIS 14803), administered to chronic hepatitis C patients. J Hepatol 2006, 44:88–96.
Otto GA, Puglisi JD: The pathway of HCV IRES-mediated translation initiation. Cell 2004, 119:369–380.
Kato T, Miyamoto M, Furusaka A, et al.: Processing of hepatitis C virus core protein is regulated by its C-terminal sequence. J Med Virol 2003, 69:357–366.
Lamarre D, Anderson PC, Bailey M, et al.: An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus. Nature 2003, 426:186–189.
Reesink HW, Zeuzem S, Weegink CJ, et al.: Rapid decline of viral RNA in hepatitis C patients treated with VX-950: a phase Ib, placebo-controlled, randomized study. Gastroenterology 2006, 131:997–1002.
Sarrazin C, Kieffer TL, Bartels D, et al.: Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology 2007, 132:1767–1777.
Forestier N, Reesink HW, Weegink CJ, et al.: Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C. Hepatology 2007, 46:640–648.
Sarrazin C, Rouzier R, Wagner F, et al.: SCH 503034, a novel hepatitis C virus protease inhibitor, plus pegylated interferon alpha-2b for genotype 1 nonresponders. Gastroenterology 2007, 132:1270–1278.
Bartenschlager R, Frese M, Pietschmann T: Novel insights into hepatitis C virus replication and persistence. Adv Virus Res 2004, 63:71–180.
Afdhal N, O’Brien C, Godofsky E, et al.: Valopicitabine (NM283), alone or with peginterferon, compared to peginterferon/ribavirin (pegIFN/RBV) re-treatment in hepatitis C patients with prior non-response to pegIFN/RBV: week 24 results [abstract]. Presented at the 41st Annual Meeting of the European Association for the Study of the Liver. April 26–30, 2006; Vienna, Austria.
Roberts S, Cooksley G, Dore GJ, et al.: Results of a phase 1b, multiple dose study of R1626, a novel nucleoside analogue, targeting HCV polymerase in chronic HCV genotype 1 patients [abstract]. Presented at the 57th Annual Meeting of the American Association for the Study of Liver Diseases. October 27–31, 2006; Boston, MA.
Steinmann E, Whitfield T, Kallis S, et al.: Antiviral effects of amantadine and iminosugar derivatives against hepatitis C virus. Hepatology 2007, 46:330–338.
Whitby K, Taylor D, Patel D, et al.: Action of celgosivir (6 O-butanoyl castanospermine) against the pestivirus BVDV: implications for the treatment of hepatitis C. Antivir Chem Chemother 2004, 15:141–151.
Durantel D, Carrouee-Durantel S, Branza-Nichita N, et al.: Effects of interferon, ribavirin, and iminosugar derivatives on cells persistently infected with noncytopathic bovine viral diarrhea virus. Antimicrob Agents Chemother 2004, 48:497–504.
Gish RG, Arora S, Rajender RK, et al.: Virological response and safety outcomes in therapy-naive patients treated for chronic hepatitis C with taribavirin or ribavirin in combination with pegylated interferon alfa-2a: a randomized, phase 2 study. J Hepatol 2007, 47:51–59.
Valeant Pharmaceuticals reports VISER2 results for Viramidine [press release]. Costa Mesa, CA: Valeant Pharmaceuticals International; September 12, 2006.
Janeway CA, Jr, Medzhitov R: Innate immune recognition. Annu Rev Immunol 2002, 20:197–216.
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Takkenberg, B., de Bruijne, J., Weegink, C. et al. Novel therapies in hepatitis B and C. Curr Gastroenterol Rep 10, 81–90 (2008). https://doi.org/10.1007/s11894-008-0013-z
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DOI: https://doi.org/10.1007/s11894-008-0013-z