Conclusions
     Nezam H. Afdhal, MD, FRCPI:
     In summary, a number of novel HCV therapies were discussed at the 2007
Annual Meeting of the AASLD. Some of the major issues discussed concerning
these novel approaches include resistance, the role of ribavirin in future
regimens, the efficacy of polymerase inhibitors vs protease inhibitors, the
importance of RVR, and the optimal treatment duration.

     David R. Nelson, MD:
     The data seem to show that ribavirin is going to be a part of new
regimens, and that the use of RVR to evaluate treatment efficacy will
continue to be valid with small molecules. Moreover, 24-week regimens will
likely become standard of care.

     Certainly resistance is a new concern in the field of hepatitis C and
is of great interest to clinicians evaluating new treatment trials. We can
attempt to draw from other disciplines when addressing the issue of
resistance with HCV. However, although some of these novel therapies have
been associated with the development of resistance, it is important to
remember that unlike HIV, HCV is a curable disease with a success rate of
approximately 40% to 45% in genotype 1-infected individuals. Therefore, it
should be approached differently.

     It is believed by some investigators that the use of the drugs
associated with high rates of resistance will pose a risk to nonresponsive
or partially responsive patients by restricting their options for combating
HCV infection. However, if an investigational agent associated with high
rates of resistance allows the cure rate in genotype 1-infected patients to
increase from 45% to 65%, for example, this likely represents a significant
decrease in the future burden of hepatocellular carcinoma, for which the
resistance may well be a price worth paying. The resistance profile of the
current protease inhibitors is preferable to the lack of availability of
protease inhibitors for another 5 years. These drugs may be flawed but they
can make a difference in the lives of many patients until compounds with
better resistance profiles are available.

     Nezam H. Afdhal, MD, FRCPI:
     I agree that the significance of resistance must be assessed in the
context of the disease. In hepatitis C, resistance is not as important an
issue as it is in the case of a lifelong incurable infection such as HIV,
given that there is a real potential to improve SVR rates. Concern over
resistance should not prevent future studies with interferon alfa and
ribavirin as the backbone. Although some investigational drugs have similar
resistance profiles, the use of multiple therapies should help to limit the
emergence of multidrug-resistant virus. Furthermore, clinicians are aware
that patients who experience virologic breakthrough or fail to achieve RVR
are unlikely to respond to the particular therapy used, allowing therapy to
be discontinued promptly and other strategies considered.