24 hour/ 1 log drop = GOOD!

[orleans]

Very Early Response to Interferon-based Therapy for Hepatitis C Is Apparent within the First 24 Hours
Last updated:26June2008

By Liz Highleyman hivandhepatitis.com

Many experts recommend that interferon-based therapy for chronic hepatitis C should be discontinued if early virological response (EVR) is not evident by week 12 of treatment, as this predicts a low likelihood of achieving sustained response. Studies have shown that rapid virological response (RVR) at week 4 is also a strong predictor of sustained virological response (SVR).

But, according to a study presented at the recent Digestive Disease Week 2008 conference in San Diego, it may be possible to predict ultimate outcomes even sooner - perhaps within the first 24 hours - thereby sparing non-responders additional side effects and expense.

In the present study, the investigators sought to characterize the earliest genomic and virological responses to treatment in HCV patients, and to establish a correlation between early viral kinetics and gene expression and ultimate virological response.

The analysis included 25 patients with chronic hepatitis C (14 men, 11 women, all Caucasian, median age 40 years) who started standard therapy with pegylated interferon plus ribavirin after November 2006; 15 had HCV genotype 1 and 10 had genotype 3.

Blood samples were taken immediately prior to commencement of treatment and again at 6, 12, and 24 hours. Polymerase chain reaction (RT-PCR) testing was performed on peripheral blood mononuclear cells (PBMCs) from 10 patients on a selection of genes previously associated with response to interferon therapy.

Results

• 21 study participants exhibited a dramatic and consistent decline in HCV RNA during the first 24 hours of treatment, exceeding a 10-fold (1-log) drop (median 1.5 log10 IU/mL).

• 4 patients, all with genotype 1, exhibited a slow first phase response of <1 log10 IU/mL and ultimately failed to achieve sustained response.

• 1 patient with genotype 3 achieved undetectable HCV at 24 hours.

• The greatest decline in HCV RNA occurred between 12 and 24 hours.

• There was a significant difference in the 24-hour decline between patients with genotypes 1 and 3 (P=0.02).

• There was also a significant association between 24-hour log HCV RNA decline and response at 12 weeks (P=0.007).

• Genetic analysis revealed a significant increase in the expression of OAS 1, TNF, IRF-7, Mx-1, STAT 1, and IL-6 over 24 hours.

• There was a significant difference in TNF expression at 24 hours between ultimate responders and nonresponders (P<0.05).

• There was an overall trend towards a higher fold change in interferon response gene expression at both 12 and 24 hours in responders.

Conclusion

"These early changes in gene expression and viral kinetics illustrate treatment effect within the first 24 hours," the investigators concluded. "Correlation of viral kinetics with treatment outcome can give an indication of ultimate outcome, allowing modification or withdrawal of treatment at an early stage."

5/30/08

Reference
EJ Devitt, JA Browne, C Walsh, and others. Very early viral response to treatment of hepatitis C virus (HCV) with pegylated interferon and ribavirin: the first 24 hours. Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22, 2008. Abstract S1005.

[jmjm530]

I've heard for some time that the greatest drop is often within the first 24 hours, so its not surprising that if you don't achieve a one-log drop in that period you may eventually be a non-responder. (I had close to a two-log drop at week 1 and my NP told me I was probably very close to UND at the 24-hour mark).  Frankly, Im surprised more study hasn't been done with these early viral kinetics to spare non-responders all that time in treatment, but at least more and more docs are looking at the four-week PCR a lot more seriously, as opposed to waiting until week 12 or even beyond.

What I don't get from the abstract is how this translates into SVR odds for the vast majority of folks who do get that one-log drop or better. Perhaps that's in the full-text study but possibly too small a group to make too many tx projections.

[Marcia2202]

This disease is completely insane... I mean, you never know where you're at. The more interested one becomes, the more complicated it gets. And then, we shouldn't forget, this is only one study of the kind... But it does make sense.

I think I'm gonna go all the way and being a 3, if I'm only UND at week 12, I'll go for 48. I really wanna get this thing out of the way.

Marcia

[gauf]

I would have done the 24 hr pcr. But, I would not abandon treatment until the the 4 week. That is still the our best indicator.

[orleans]

And a little scary. I am tempted to do a PCR at 24 hours, no 1 log drop, no treatment. What ya think Jim? Not enough info huh? If I were not stage 3 I might really consider it with the new drugs coming on line and all. jerry

[Marcia2202]

Very interesting!

Marcia