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Issue 8, 2007
HOT TOPICS IN VIRAL HEPATITIS
New antivirals in hepatitis C
| Publ. date: | 2007 |
| ISBN: | 978-88-89881-54-5 |
| ISSN: | 1973-9648 |
| E-ISSN: | 2036-0932 |
| DOI: | 10.4147/HTV-070800 |
Abstract
As current therapy for chronic hepatitis C, based on the combination of pegylated (PEG) interferon alfa and ribavirin, is successful only in about half of all patients for whom it is indicated, more effective and better tolerated therapeutic regimens are needed.
Over the past several years, significant progress has been made in our understanding of the life cycle of HCV. As a result of these advances, a number of small-molecule oral drugs that target specific enzymes essential for propagation of HCV are currently in preclinical or clinical stages of development. The arrival of these so-called STAT-C agents (specifically targeted antiviral therapy for hepatitis C), expected within 3 to 5 years, is likely to be the most significant advance in HCV treatment since PEG-interferon alfa. Notwithstanding such optimism, a number of limitations have already emerged, with drug resistance and tolerability being the most problematic.
Moreover, numerous agents able to induce an immune response to HCV are currently under development. Among these, the manipulation of immune system effectors such as Toll-like receptors, new forms of interferons, and therapeutic vaccines are exciting examples and represent a promising therapeutic approach owing to their avoidance of drug resistance.
Furthermore, it is now possible to interfere with the processes leading to fibrosis. This approach is particularly important for patients with progressive liver disease who are nonresponsive to antiviral treatment, in HCV/HIV co-infection, and for patients with recurrence of HCV-related hepatitis after liver transplantation.
Table of contents
Foreword
This issue is devoted to the treatment of hepatitis C virus (HCV) infection with new antivirals. The three chapters analyze many different approaches to the control of HCV infection and liver disease progression, including new molecules targeting the viral life cycle, new immunomodulating agents, and the possibility of controlling hepatic fibrosis.
Current therapy of chronic hepatitis C, based on the combined administration of pegylated interferon-alfa and ribavirin, is successful in about half of the patients for whom it is indicated. Barriers to therapy are still significant and range from relevant comorbidities to patients’ refusal, mostly due to fear of the frequently occurring side effects. Unfortunately, patients with advanced liver disease and most in need of treatment are also the most unlikely candidates to receive it. Thus, more effective and better tolerated therapeutic regimens are needed.
The availability of robust systems to cultivate HCV in vitro, attained only in recent years, and the progress in elucidating the viral life cycle at the molecular level, have made possible the development of several antivirals targeting key steps in HCV replication. Some of these molecules are now being evaluated in clinical trials and may reach the market shortly. Several other pproaches are being considered. The manipulation of immune system effectors, like the Toll-like receptors, is an exciting example. Furthermore, it is now possible to interfere with the processes leading to fibrosis. It is very likely that in the future, optimal therapy for HCV will encompass several of these approaches combined together, and it is not unrealistic to envisage the global eradication of HCV within a few decades.
ARTICLES
New inhibitors of the HCV life cycle
Roniel Cabrera, David R. Nelson
New immunomodulators in the treatment of chronic hepatitis C: hopes and concerns
Yves Horsmans
Antifibrosing agents
Fabio Marra
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Editor-in-chief
Francesco Negro - DO, MPH
Over the last 20 years, there have been great strides in the treatment of viral hepatitis. Both the discovery of the hepatitis C and E viruses, with the characterization of their genomes, and the avai...
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