merryBe

[desrt]

Please check out the slide set by Dr. Mitchell Shiffman released today at Clinical Care Options.

clinicaloptions.com

[desrt]

I hope K. Lindahl can do a larger study someday. You've worked those ten anemic Swedes pretty hard this last year and they need a rest.
Lindahl may be a pioneering genius in the field of HCV tx, but she'll never get the recognition she deserves with numbers that small. The UCSF pot study had way more patients and showed way better results - 3x as many SVRs among occasional smokers over non-smokers - Lindahl merely doubled response rates.

Which only goes to show small studies don't have a lot of significance statistically.

[jmjm530]

You are talking about the small Swedish Pilot Study where 9 out of 10 genotype 1 participants were SVR.

Special HPLC testing (not available here) was used to help measure a pre-determined serum riba level originally established by a pharmakentic formula based on kidney function as opposed to weight.

The treatment was very rough, with 2 out of the 10 particpants requiring two blood transfusions each.

But that aside, the riba was high-dosed from the start of treatment, not later in treatment as would be your case as a null responder. And even if you wanted to try high doses per the study, unless you had access to these specialized tests, you wouldn't have an accurate way of figuring out your serum riba levels, with the degree of anemia being the only measure, and much cruder than the actual HPLC tests.

That said, an HPLC test at this point might be of some interest -- perhaps for the future -- in terms of seeing how much riba you did absorb, but finding the test will not be easy and may require either  a trip to Europe (while still on the riba) or somehow shipping it to a lab frozen, I presume. This could end up being a small undertaking.

Personally, I'd go with the advice your liver specialist on this one, as if I remember correctly you've been classified as a null responder.

-- Jim

[merryBe]

I would normally already concur, and having missed no doses did give this my best shot.

One wrench though is having that secondary infection show up, and then throwing back amoxicillin for over two weeks, and again today (each dental visit)...which I cannot believe di not lower my white count, mess with interferon, and perhaps stop the forward progress.

Also wondering how a woman doctor in France got a 90% SRV by monitoring serum Riba levels and yet no one here has the kahunas to treat this way??

not ready to throw it in until I know it's hopeless.
still appreciate the info, but it changes weekly.

also shwartz (2nd opinion) said 20% more will cure with extended tx...latest info...so it looks like new stats are showing up.
Mary

[jmjm530]

   (1) Rates of SVR in patients with genotype 1 infection who achieve an RVR do not appear to be affected by reduction of ribavirin dose.
    (2)  The initial management strategy for patients with RVR who develop adverse events should be to consider reduction of the doses of ribavirin and/or peginterferon alfa so that these patients can hopefully complete the recommended duration of therapy.
    (3) It has been hypothesized that some patients with a partial treatment response may achieve undetectable HCV RNA if switched to or retreated with a more itensive peginterferon alfa regimen.
    (4) Patients who do not achieve an EVR will not achieve undetectable HCV RNA with continued treatment and are defined as having a null response. This is an indication for stopping treatment.
   (5) An important reason for viral breakthrough may be missing doses of peginterferon alfa and/or ribavirin.
    
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I think the key finding here in your situation is #4, which once again suggests that if you don't have a two-log drop by week 12, then not much is going to work, including extending treatment. Again -- haven't gone though all the slides so I'm assuming Dr. F. is using standard definitions of EVR and Non-response, etc.

I find #'s 1,2 and 5 in conflict. If breakthough can be caused by missed doses, why not make all attempts for a patient to stay on full-doses by using helper drugs, especially in those with signficant liver damage. Again, haven't seen the whole slide set, so just extrapolating here.

[jmjm530]

Thanks for the heads up. Haven't had time to wade through the slide set, but here are the conclusions and a few comments:

Summary of Clinical Implications

    * A patient must respond virologically and achieve undetectable HCV RNA (< 50 IU/mL) to achieve an SVR.
    * Patients who do not respond virologically cannot achieve an SVR by continuing the same treatment for a longer period of time.
    * Patterns of virologic response and nonresponse be recognized by assessing HCV RNA at monthly intervals until the HCV RNA has become undetectable or a nonresponse pattern has been defined (Week 24).
    * Up to 90% of patients with RVR achieve SVR if they remain on treatment for 48 weeks for HCV genotype 1 infections and 24 weeks for HCV genotype 2 and 3 infections.
    * Rates of SVR in patients with genotype 1 infection who achieve an RVR do not appear to be affected by reduction of ribavirin dose.
    * The initial management strategy for patients with RVR who develop adverse events should be to consider reduction of the doses of ribavirin and/or peginterferon alfa so that these patients can hopefully complete the recommended duration of therapy.
    * It is important to continue to monitor HCV RNA through Week 24 even if the patient does not achieve undetectable HCV RNA during that time to allow for identification of partial virologic response.
    * It has been hypothesized that some patients with a partial treatment response may achieve undetectable HCV RNA if switched to or retreated with a more intensive peginterferon alfa regimen.
    * Patients who do not achieve an EVR will not achieve undetectable HCV RNA with continued treatment and are defined as having a null response. This is an indication for stopping treatment.
    * An important reason for viral breakthrough may be missing doses of peginterferon alfa and/or ribavirin.
    * Patients fail to achieve SVR for several different reasons. All but one of these factors, null response, can potentially be overcome during retreatment.
    * Only those patients who have a known and correctable reason for their previous treatment failure should be considered for retreatment.
    * The outcomes of retreatment may be maximized by improving education and awareness about adverse effects of peginterferon alfa and ribavirin, having a stronger commitment to therapy, or seeking care from a more experienced and/or attentive treatment provider.