Review Article: Novel Therapeutic Options for Chronic Hepatitis C

Evangelos Cholongitas; George V. Papatheodoridis


Aliment Pharmacol Ther. 2008;27(10):866-884. 

In This Article


Several novel agents with encouraging preliminary results have already reached or will soon enter into advanced clinical development programmes to demonstrate definitely their usefulness in the treatment of CHC. Aside from the safety and efficacy, the success of these new agents will be influenced by their ability to inhibit all viral variants and prevent the emergence of escape mutants. To date, the NS5B RdRp and the NS3/4A protease have received more attention as anti-HCV targets. However, it is evident that monotherapy with any anti-viral will be unlikely to eradicate HCV and combinations of several agents with different modes of action against viral and possibly host targets will be needed to prevent the emergence of drug-resistant viral variants. Thus, additional research is required to determine proper dosing and treatment strategies to overcome drug resistance. On the basis of recent clinical trials, the combination of HCV inhibitors with PEG-IFNα with or without RIB synergistically inhibits viral replication and facilitates viral clearance. Further studies will determine whether the superior responses with these new combinations may offer greater SVR rates allowing shorter treatment durations and avoiding viral resistance. However, the great advance in the anti-HCV treatment will come from effective strategies that will not include poorly tolerated and/or frequently contraindicated agents, like IFNα and/or RBV.

The advances and future improvement in in vitro culture systems should lead to a better understanding of the host-viral interaction and will boost the search for new HCV therapeutics, whereas more sensitive HCV-RNA assays will be available to differentiate better responders from relapsers or nonresponders. However, the aim should always be the transformation of very promising substances in culture systems into effective and safe drugs in clinical trials. Given that many agents are being developed, it is hoped that the future standard of care will target multiple points of the viral life cycle and host immune response. Ideally, the newer compounds should provide a more effective and more tolerable therapy to all chronic HCV patients.

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