Treatment of Chronic Hepatitis C Infection with Peginterferons Plus Ribavirin

Interferon monotherapy provided the first hope for patients with chronic hepatitis C that the virus could be permanently eradicated. An important development in treating this disease was the recognition that the effects of interferon could be greatly enhanced by combining it with ribavirin, a nucleoside analogue. This combination regimen essentially doubled the sustained virological response rates seen with interferon alone. Recently, modified forms of interferon have been developed that-when used in combination with ribavirin-demonstrate even better efficacy. Thus, peginterferon alfa-2a (Hoffman La-Roche, Nutley, NJ) and peginterferon alfa-2b (Schering-Plough, Kenilworth, NJ) are the latest innovations for the treatment of chronic hepatitis C. The addition of a polyethylene glycol molecule to the native interferon protein favorably alters the pharmacokinetic profile, allowing for once-weekly administration, and leads to superior efficacy compared to standard interferon preparations. This article reviews the data from clinical trials of peginterferon alfa-2a and peginterferon alfa-2b.

KEYWORDS

Hepatitis C - treatment - interferon - peginterferon

REFERENCES

• 1 Manns M P, McHutchison J G, Gordon S C 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
• 2 Fried M W, Shiffman M L, Reddy K R et al.. Combination of peginterferon alfa-2a plus ribavirin in patients with chronic hepatitis C virus infection.  N Engl J Med. 2002;  347 975-982
• 3 Hadziyannis S J, Sette Jr H, Morgan T R et al.. Peginterferon-α2a and ribavirin combination therapy in chronic hepatitis C. A randomized study of duration and ribavirin dose.  Ann Intern Med. 2004;  140 346-355
• 4 National Institutes of Health Consensus Development . Conference Statement: Management of hepatitis C 2002 (June 10-12, 2002).  Gastroenterology. 2002;  123 2082-2099
• 5 Pawlotsky J M. Use and interpretation of virological tests for hepatitis C.  Hepatology. 2002;  36 S65-S73
• 6 Peginterferon alfa-2b .Package insert: Dosage and administration. Kenilworth, NJ; Schering Corporation 2002
• 7 Russo M W, Zacks S L, Fried M W. Management of newly diagnosed hepatitis C virus infection.  Cleve Clin J Med. 2003;  70(Suppl 4) S14-S20
• 8 McHutchison J G, Gordon S C, Schiff E R et al.. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group.  N Engl J Med. 1998;  339 1485-1492
• 9 Marcellin P, Brillanti S, Cheinquer H et al.. Peginterferon alfa-2a (40 KD) (Pegasys) plus ribavirin (copegus) is an efficacious and safe treatment for chronic hepatitis C (CHC) in patients with compensated cirrhosis.  J Hepatol. 2003;  38 154 (Abst)
• 10 Layden-Almer J E, Layden T J. Viral kinetics in hepatitis C virus: special patient populations.  Semin Liver Dis. 2003;  23(Suppl 1) 29-33
• 11 Layden-Almer J E, Ribeiro R M, Wiley T, Perelson A S, Layden T J. Viral dynamics and response differences in HCV-infected African American and white patients treated with IFN and ribavirin.  Hepatology. 2003;  37 1343-1350
• 12 Lutchman G, Hoofnagle J H. Viral kinetics in hepatitis C.  Hepatology. 2003;  37 1257-1259
• 13 Russo M W, Fried M W. Hepatitis C therapy: Guidelines for stopping therapy.  Curr Gastroenterol Rep. 2004;  , (in press)
• 14 Davis G L, Wong J B, McHutchison J G et al.. Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C.  Hepatology. 2003;  38 645-652
• 15 Davis G L. Monitoring of viral levels during therapy of hepatitis C.  Hepatology. 2002;  36 S145-S151
• 16 Pawlotsky J M, Bouvier-Alias M, Hezode C et al.. Standardization of hepatitis C virus RNA quantification.  Hepatology. 2000;  32 654-659
• 17 McHutchison J G, Manns M, Patel K et al.. Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C.  Gastroenterology. 2002;  123 1061-1069
• 18 Ferenci P, Shiffman M L, Fried M W et al.. Early prediction of response to 40KDA peginterferon alfa-2a (PEGASYS) plus ribavirin in patients with chronic hepatitis C.  Hepatology. 2001;  34 351A
• 19 Fried M W. Side effects of therapy for hepatitis C and their management.  Hepatology. 2002;  36 S237-S244
• 20 Russo M W, Fried M W. Side effects of therapy for chronic hepatitis C.  Gastroenterology. 2003;  124 1711-1719
• 21 Afdhal N H, Dieterich D T, Pockros P J et al.. Epoetin alfa treatment of anemic HCV-infected patients allows for maintenance of ribavirin dose, increases hemoglobin levels, and improves quality of life vs placebo: a randomized, double-blind multicenter study.  Gastroenterology. 2003;  124 505 , (Abst)
• 22 Shiffman M, Di Bisceglie A M, Lindsay K L et al.. Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment.  Gastroenterology. 2004;  126 1015-1023
• 23 Jacobson I M, Russo M W, Brown Jr R S et al.. Pegylated interferon alfa-2b plus ribavirin in patients with chronic hepatitis C: a trial in prior interferon non-responders to interferon monotherapy or combination therapy and in combination therapy relapsers.  Gastroenterology. 2002;  122 79 (Abst)