Very Early Response to Interferon-based Therapy for Hepatitis C Is Apparent with

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Very Early Response to Interferon-based Therapy for Hepatitis C Is

Apparent within the First 24 Hours

By Liz Highleyman

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. "