Mederacke I, Wedemeyer H

Language: English
References: 14
Page: 166-168
PDF size: 60.68 Kb.

Text Extraction

Treatment of chronic hepatitis C has significantly improved over the last two decades as - depending on the HCV genotype - 40-90% of patients achieve a sustained virological response (SVR). However, treatment with (pegylated-) interferon alfa (PEG-IFN) and ribavirin (RBV) is still associated with frequent and sometimes severe side effects and many patients cannot be treated because of contraindications. A major step forward in the therapy of HCV infection is expected by the approval of new direct inhibitors of HCV replication. Several compounds, mainly inhibitors of the HCV NS3/4A protease and NS5B polymerase, are currently in phase II and III trials and the first HCV protease inhibitors will hopefully be licensed in 2011/12.

REFERENCES

1. Manns MP, Wedemeyer H, Cornberg M. Treating viral hepatitis C: efficacy, side effects, and complications. Gut 2006; 55: 1350-1359.

2. Mederacke I, Wedemeyer H, Manns MP. Boceprevir, an NS3 serine protease inhibitor of hepatitis C virus, for the treatment of HCV infection. Current Opinion in Investigational Drugs 2009; 10: 181-189.

3. Manns MP, Foster GR, Rockstroh JK, Zeuzem S, Zoulim F, Houghton M. The way forward in HCV treatment—finding the right path. Nat Rev Drug Discov 2007; 6: 991-1000.

4. Rossignol JF, Elfert A, El Gohary Y, Keeffe EB. Improved virologic response in chronic hepatitis C genotype 4 treated with nitazoxanide, peginterferon, and ribavirin. Gastroenterology 2009; 136: 856-862.

5. Korba BE, Montero AB, Farrar K, Gaye K, Mukerjee S, Ayers MS, Rossignol JF. Nitazoxanide, tizoxanide and other thiazolides are potent inhibitors of hepatitis B virus and hepatitis C virus replication. Antiviral Research 2008; 77: 56-63.

6. Elazor M, Liu M, McKenna S, Liu P, Gehrig EA, Elfert A, Puglisi J, Rossignol JF, Glenn JS. Nitazoxanide (Ntz) is an inducer Eif2A and Pkr phosphorylation. Hepatology 2008; 48: 1151A.

7. Gale M, Katze MG. Molecular mechanisms of interferon resistance mediated by viral-directed inhibition of PKR, the interferon-induced protein kinase. Pharmacology & Therapeutics 1998; 78: 29-46.

8. Rossignol JF, Kabil SM, El Gohary Y, Elfert A, Keeffe EB. Clinical trial: randomized, double-blind, placebo-controlled study of nitazoxanide monotherapy for the treatment of patients with chronic hepatitis C genotype 4. Alimentary Pharmacology & Therapeutics 2008; 28: 574-580.

9. Khuroo MS, Khuroo MS, Dahab ST. Meta-analysis: a randomized trial of peginterferon plus ribavirin for the initial treatment of chronic hepatitis C genotype 4. Aliment Pharmacol Ther 2004; 20: 931-938.

10. Muir AJ, Bornstein JD, Killenberg PG. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med 2004; 350: 2265-2271.

11. Bacon B, Shiffman M, Lim J, Berman A, Rustgi V, Keeffe E. Phase 2 randomized, double-blind, placebo-controlled study of nitazoxanide plus peginterferon and ribavirin in HCV genotype 1 patients: Interim analysis shows increase in EVR. Journal of Hepatology 2009: 50, S381.

12. Shiffman M, Ahmed A, Jacobson I, Pruitt R, Keeffe E. Phase 2 randomized, double-blind, placebo-controlled study of nitazoxanide with peginterferon alfa-2a and ribavirin in nonresponders (NR) with chronic HCV genotype 1: Week 28 interim analysis. Journal of Hepatology 2009: 50, S385.

13. Keeffe E, Rossignol J, Elfert A, Abdelatif S, Cravens L, Phuong T. Controlled release tablet improves pharmacokinetcs, viral kinetics and tolerability of nitazoxanide for treatment of chronic hepatitis C (Abstract). Hepatology International 2009; 3: 49.

14. Rossignol JF, Hidalgo H, Feregrino M, Higuera F, Gomez WH, Romero JL, Padierna J, Geyne A, Ayers MS. A double-’blind’ placebo-controlled study of nitazoxanide in the treatment of cryptosporidial diarrhoea in AIDS patients in Mexico. Trans R Soc Trop Med Hyg 1998; 92: 663-666.