Research Article | DOI: https://doi.org/BRCA-RA-26-42
Antiviral therapies for hepatitis C infection: current and new developments
Abstract
The majority of HCV strains in Europe and North America are genotype-1, and up to 75% of individuals with chronic infection can be cured with recently approved direct acting antivirals. New antiviral treatments offer longer treatment durations, better tolerability, increased virological response, and possibly even the opportunity to stop using interferon. The primary treatment drugs, such as telaprevir and boceprevir, that are currently part of the standard of care are highlighted in this study. It then assesses the mechanisms underlying newly developed medications, as well as the response rates observed in existing research. Lastly, it looks ahead to the not-too-distant future to examine treatment plans that include interferon-free medicines and agent combinations, and in which patients They could end up being the most successful.
References
-
Chung RT. A watershed moment in the treatment of hepatitis C. N Engl J Med 2012; 366: 273–275.
View at Publisher | View at Google Scholar -
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: 529–538.
View at Publisher | View at Google Scholar -
Lavanchy D. The global burden of hepatitis C. Liver Int 2009; 29: 74–81.
View at Publisher | View at Google Scholar -
Ly KN, Xing J, Klevens RM, Jiles RB, Ward JW, Holmberg SD. The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Ann Intern Med 2012; 156: 271–278.
View at Publisher | View at Google Scholar -
Fried MW. Side effects of therapy of hepatitis C and their management. Hepatology 2002; 36: S237–244.
View at Publisher | View at Google Scholar -
Sulkowski MS, Cooper C, Hunyady B, Jia J, Ogurtsov P, Peck-Radosavljevic M, Shiffman ML, Yurdaydin C, Dalgard O. Management of adverse effects of Peg-IFN and ribavirin therapy for hepatitis C. Nat Rev Gastroenterol Hepatol 2011; 8: 212–223.
View at Publisher | View at Google Scholar -
Noureddin M, Ghany MG. Pharmacokinetics and pharmacodynamics of peginterferon and ribavirin: implications for clinical efficacy in the treatment of chronic hepatitis C. Gastroenterol Clin North Am 2010; 39: 649–658.
View at Publisher | View at Google Scholar -
Reddy KR, Nelson DR, Zeuzem S. Ribavirin: current role in theoptimal clinical management of chronic hepatitis C. Hepatol 2009; 50: 402–411.
View at Publisher | View at Google Scholar -
Pearlman BL, Traub N. Sustained virologic response to antiviral therapy for chronic hepatitis C virus infection: a cure and so much more. Clin Infect Dis 2011; 52: 889–900.
View at Publisher | View at Google Scholar -
Grebely J, Matthews GV, Dore GJ. Treatment of acute HCV infection. Nat Rev Gastroenterol Hepatol 2011; 8: 265–274.
View at Publisher | View at Google Scholar -
Doyle JS, Sacks-Davis R, Hellard ME. Acute hepatitis C infection: new approaches to surveillance, treatment and prevention. Curr Hepatitis Rep 2012; doi: 10.1007/s11901-012-0143-5. in press.
View at Publisher | View at Google Scholar -
Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 347: 975–982.
View at Publisher | View at Google Scholar -
Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. 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.
View at Publisher | View at Google Scholar -
Lau JY, Tam RC, Liang TJ, Hong Z. Mechanism of action ofribavirin in the combination treatment of chronic HCV infection. Hepatology 2002; 35: 1002–1009.
View at Publisher | View at Google Scholar -
Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009; 461: 399–401.
View at Publisher | View at Google Scholar -
Holmes JA, Sievert W, Thompson AJ. IL28B polymorphism and genetic biomarkers of viral clearance in hepatitis C virus infection. Biomark Med 2011; 5: 461–478.
View at Publisher | View at Google Scholar -
Thompson AJ, Muir AJ, Sulkowski MS, Ge D, Fellay J, Shianna KV, Urban T, Afdhal NH, Jacobson IM, Esteban R, Poordad F, Lawitz EJ, McCone J, Shiffman ML, Galler GW, Lee WM, Reindollar R, King JW, Kwo PY, Ghalib RH, Freilich B, Nyberg LM, Zeuzem S, Poynard T, Vock DM, Pieper KS, Patel K, Tillmann HL, Noviello S, Koury K, Pedicone LD, Brass CA
View at Publisher | View at Google Scholar -
Sarrazin C, Susser S, Doehring A, Lange CM, Muller T, Schlecker C, Herrmann E, Lotsch J, Berg T. Importance of IL28B gene polymorphisms in hepatitis C virus genotype 2 and 3 infected patients. J Hepatol 2011; 54: 415–421.
View at Publisher | View at Google Scholar -
Vezali E, Aghemo A, Colombo M. A review of the treatment of chronic hepatitis C virus infection in cirrhosis. Clin Ther 2010; 32: 2117–2138.
View at Publisher | View at Google Scholar -
Kau A, Vermehren J, Sarrazin C. Treatment predictors of a sustained virologic response in hepatitis B and C. J Hepatol 2008; 49: 634–651.
View at Publisher | View at Google Scholar -
European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatitis C virus infection. J Hepatol 2011; 55: 245–264.
View at Publisher | View at Google Scholar -
Berg T, Sarrazin C, Herrmann E, Hinrichsen H, Gerlach T, Zachoval R, Wiedenmann B, Hopf U, Zeuzem S. Prediction of treatment outcome in patients with chronic hepatitis C: significance of baseline parameters and viral dynamics during therapy. Hepatology 2003; 37: 600–609.
View at Publisher | View at Google Scholar -
Davis GL, Wong JB, McHutchison JG, Manns MP, Harvey J, Albrecht J. Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology 2003; 38: 645–652.
View at Publisher | View at Google Scholar -
Camma C, Cabibbo G, Bronte F, Enea M, Licata A, Attanasio M, Andriulli A, Craxi A. Retreatment with pegylated interferon plus ribavirin of chronic hepatitis C non-responders to interferon plus ribavirin: a meta-analysis. J Hepatol 2009; 51: 675–681.
View at Publisher | View at Google Scholar -
Jensen DM, Marcellin P, Freilich B, Andreone P, Di Bisceglie A, Brandao-Mello CE, Reddy KR, Craxi A, Martin AO, Teuber G, Messinger D, Thommes JA, Tietz A. Re-treatment of patients with chronic hepatitis C who do not respond to peginterferon-alpha2b: a randomized trial. Ann Intern Med 2009; 150: 528–540.
View at Publisher | View at Google Scholar -
Poynard T, Colombo M, Bruix J, Schiff E, Terg R, Flamm S, Moreno-Otero R, Carrilho F, Schmidt W, Berg T, McGarrity T, Heathcote EJ, Goncales F, Diago M, Craxi A, Silva M, Bedossa P, Mukhopadhyay P, Griffel L, Burroughs M, Brass C, Albrecht J. Peginterferon alfa-2b and ribavirin: effective in patients with hepatitis C who failed interferon alfa/ribavirin therapy. Gastroenterology 2009; 136: 1618–1628.
View at Publisher | View at Google Scholar -
Torriani FJ, Rodriguez-Torres M, Rockstroh JK, Lissen E, Gonzalez-García J, Lazzarin A, Carosi G, Sasadeusz J, Katlama C, Montaner J, Sette H, Passe S, De Pamphilis J, Duff F, Schrenk UM, Dieterich DT. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med 2004; 351: 438–450.
View at Publisher | View at Google Scholar -
Hellard M, Sacks-Davis R, Gold J. Hepatitis C treatment for injection drug users: a review of the available evidence. Clin Infect Dis 2009; 49: 561–573.
View at Publisher | View at Google Scholar -
Dore GJ, Hellard M, Matthews GV, Grebely J, Haber PS, Petoumenos K, Yeung B, Marks P, Van Beek I, McCaughan G, White P, French R, Rawlinson W, Lloyd AR, Kaldor JM. Effective treatment of injecting drug users with recently acquired hepatitis C virus Infection. Gastroenterology 2010; 138: 123–135.
View at Publisher | View at Google Scholar -
Pawlotsky JM, Chevaliez S, McHutchison JG. The hepatitis Cvirus life cycle as a target for new antiviral therapies. Gastroenterology 2007; 132: 1979–1998.
View at Publisher | View at Google Scholar -
Moradpour D, Penin F, Rice CM. Replication of hepatitis C virus. Nature reviews. Microbiology 2007; 5: 453–463.
View at Publisher | View at Google Scholar -
Jazwinski AB, Muir AJ. Emerging therapies in hepatitis C: dawn of the era of the direct-acting antivirals. Gastroenterol Clin North Am 2011; 40: 481–494.
View at Publisher | View at Google Scholar -
Pockros PJ. New direct-acting antivirals in the development for hepatitis C virus infection. Therap Adv Gastroenterol 2010; 3: 191–202.
View at Publisher | View at Google Scholar -
Lee LY, Tong CY, Wong T, Wilkinson M. New therapies for chronic hepatitis C infection: a systematic review of evidence from clinical trials. Int J Clin Pract 2012; 66: 342–355.
View at Publisher | View at Google Scholar -
Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniukiene V, Brass CA, Albrecht JK, Bronowicki JP. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 2011; 364: 1195–1206.
View at Publisher | View at Google Scholar -
Foote BS, Spooner LM, Belliveau PP. Boceprevir: a protease inhibitor for the treatment of chronic hepatitis C. Ann Pharmacother 2011; 45: 1085–1093.
View at Publisher | View at Google Scholar -
Susser S, Welsch C, Wang Y, Zettler M, Domingues FS, KareyU, Hughes E, Ralston R, Tong X, Herrmann E, Zeuzem S, Sarrazin C. Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus-infected patients. Hepatology 2009; 50: 1709–1718.
View at Publisher | View at Google Scholar -
Sarrazin C, Kieffer TL, Bartels D, Hanzelka B, Muh U, Welker M, Wincheringer D, Zhou Y, Chu HM, Lin C, Weegink C, Reesink H, Zeuzem S, Kwong AD. Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology 2007; 132: 1767–1777.
View at Publisher | View at Google Scholar -
Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S, Poordad F, Goodman ZD, Sings HL, Boparai N, Burroughs M, Brass CA, Albrecht JK, Esteban R. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med 2011; 364: 1207–1217.
View at Publisher | View at Google Scholar -
Kwo PY, Lawitz EJ, McCone J, Schiff ER, Vierling JM, Pound D, Davis MN, Galati JS, Gordon SC, Ravendhran N, Rossaro L, Anderson FH, Jacobson IM, Rubin R, Koury K, Pedicone LD, Brass CA, Chaudhri E, Albrecht JK. Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial. Lancet 2010; 376: 705–716.
View at Publisher | View at Google Scholar -
Vierling JM. Efficacy of boceprevir in prior null responders to peginterferon/ribavirin: the PROVIDE Study. Hepatology 2011; 54 (Suppl. 1): A931.
View at Publisher | View at Google Scholar