Hepatitis C Patients Who Fail to Respond or Relapse Following Therapy With Pegyl

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Ask the Experts about Liver Disease

From Medscape Gastroenterology

Hepatitis C Patients Who Fail to Respond or Relapse Following Therapy With

Pegylated Interferon and Ribavirin

Question

What therapies are on the horizon for patients with hepatitis C who fail to

respond or relapse following therapy with pegylated interferon and

ribavirin?

Response from Bernstein, MD

Chief, Digestive Disease Institute, North Shore University Hospital-Long

Island Jewish Medical Center, Manhasset, New York; Associate Professor of

Medicine, New York University School of Medicine, New York, NY

This is one of the most important questions in the field of hepatitis C.

There is currently tremendous excitement regarding new therapies in

development for the treatment of hepatitis C virus (HCV) infection, and many

new products are currently being investigated. That being said, at present,

there are no new therapies available outside of clinical trials and we still

do not have evidence that any of the newer therapies will be more effective

than what currently exists.

The development of new therapies for nonresponders and relapsers to

pegylated interferon and ribavirin-based treatment focuses on 2 main

classes: newer interferons and small molecules. Data have been presented on

a novel recombinant protein consisting of a larger interferon bound to

albumin that can be given in dose intervals of every 2 weeks rather than the

standard once-a-week administration. This new product is currently being

evaluated in combination with ribavirin for the treatment of hepatitis C

infection.

Small molecules are oral agents that fall into 2 major categories: protease

inhibitors and polymerase inhibitors. Both types of compounds prevent viral

replication by specifically inhibiting either a protease or a polymerase

molecule involved in the viral replication cycle. These compounds have been

shown to dramatically decrease HCV levels when used alone for short periods

of time. Currently, these agents are being evaluated in clinic trials in

combination with pegylated interferon and ribavirin.

This above is a brief view into the types of new therapies on the horizon

for the treatment of patients with hepatitis C. Although there is

significant excitement over these compounds in development, only time will

tell as to whether they are effective. It does appear, however, that the

future of hepatitis C therapy will involve the use of some of these newer

treatments in combination with the current standard of pegylated interferon

and perhaps ribavirin.

Posted 03/02/2007

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Suggested Readings

Balan V, DR, Sulkowski MS, et al. A phase I/II study evaluating

escalating doses of recombinant human albumin-interferon-alpha fusion

protein in chronic hepatitis C patients who have failed previous

interferon-alpha-based therapy. Antivir Ther. 2006;11:35-45.

Lin C, Kwong AD, Perni RB. Discovery and development of VX-950, a novel,

covalent, and reversible inhibitor of hepatitis C virus NS3.4A serine

protease. Infect Disord Drug Targets. 2006;6:3-16.

Liu Y, Jiang WW, Pratt J, et al. Mechanistic study of HCV polymerase

inhibitors at individual steps of the polymerization reaction. Biochemistry.

2006;45:11312-11323.

Reesink HW, Zeezum 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.

http://www.medscape.com/viewarticle/552478?src=mp

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