1) I think the guidelines are fine. I do have a question as to follow up of a Genotype 1 patient who does not want treatment and also the Genotype 1 patient who fails triple therapy?
Response:
Monitoring of patients with all genotypes who do not warrant or want treatment was not addressed in the guidelines. Frequency of monitoring should be based on underlying disease severity. Patients with mild disease could be seen every six months while those with more advanced disease should be seen every three to four months; this recommendation is based on expert opinion. Patients with cirrhosis need to be considered for periodic surveillance for esophageal varices and hepatocellular carcinoma as per AASLD guidelines on Management of Esophageal Varices and Hepatocellular Carcinoma.
2) There is no consideration for IL28B testing to determine if some patients are good candidates for double therapy with Pegylated Interferon with Ribavirin vs. triple therapy. Since, compliance is a major issue with the triple therapy, providing an option with double therapy to patients who would respond well based on IL28B should be addressed.
Response:
The advantages of using PI-based treatment even in persons with IL28B genotype CC are that more persons will qualify for abbreviated therapy with telaprevir and possibly boceprevir, and there are higher SVR rates than double therapy. The advantages of treating IL28B genotype CC patients with peginterferon and ribavirin alone are fewer side effects, fewer drug-drug interactions, and lower cost. However, until cost effectiveness studies are published, we recommend the PI-based approach in most patients.
3) I am surprised there is so little commentary on which patients warrant treatment. This is a significant omission. Future guidelines and commentary should include a balanced discussion framing the pros and cons of treatment according to typical patient scenarios. These therapies are still prone to many side effects, and many patients have little urgency to treat, yet are feeling pressured to participate.
Response:
This question was beyond the scope of our mandate and will be reconsidered in the next full update to the guidelines. The issue is a highly controversial one with many different opinions. Many factors go into the decision regarding whom to treat including disease severity, likelihood of response, benefits and risks of treatment, as well as the likelihood of new therapeutic options. As efficacy and safety of therapy improves many of these factors may become less important and it is likely that most patients will become candidates for therapy.
4) The #16 recommendation of the guideline is somewhat contradictory to the #9 recommendation: In #9, the futility rule is described as the following: "telaprevir, peginterferon alfa and ribavirin should be stopped if the HCVRNA level is >1,000 IU/ml at treatment weeks 4 or 12". But in #16 it says that "the protease inhibitor should be discontinued if virological breakthrough (>1 log increase in serum HCVRNA above nadir) is observed". If telaprevir was used, there are occasions HCVRNA measured 10 times higher from nadir (e.g. Around 10 IU/ml to the hundreds but well within 1000 IU/ml futility limit) during telaprevir dosing period. If the clinician follows #9, telaprevir should be continued but if #16 was followed, telaprevir needs to be stopped. Therefore, this inconsistency needs to be addressed.
Response:
The two statements are not contradictory. To clarify, the stopping rule in #9 applies to patients who reach a virological plateau after which continued therapy would significantly increase the risk for antiviral resistance. Recommendation #16 deals with compliant patients who experience virological breakthrough signifying the emergence of antiviral resistance. Although the author is correct, among the patients with virological breakthrough, their HCV RNA may increase from undetected to 100 IU/ml and still be under the 1,000 IU/ml rule; the important point is the change from a negative to a positive test.
An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection: 2011 Practice Guideline by the American Association for the Study of Liver Diseases
These evidence-based guidelines are developed and updated regularly by a committee of hepatology experts and include recommendations of preferred approaches to the diagnostic, therapeutic, and preventive aspects of care.
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