Very Early Viral Response to Treatment of Hepatitis C Virus (HCV) with Pegylated

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Very Early Viral Response to Treatment of Hepatitis C Virus (HCV)

with Pegylated Interferon and Ribavirin: the First 24 Hours

Reported by Jules Levin

DDW, May 17-22, 2008, San Diego

Emma J Devitt, A Browne, Caroline Walsh, P Crowe

Centre for Liver Disease, Mater Misericordiae University Hospital,

Dublin, Ireland

ABSTRACT from program book

Background: Pegylated interferon and ribavirin treatment for HCV is

suboptimal with up to 60% of patients failing to respond.

Identification of non-responders soon after commencing an expensive

and difficult therapeutic regimen would be beneficial. Conversely

identification of patients responding rapidly could lead to shorter

treatment duration.

Aims: To characterise earliest genomic and virological responses to

treatment in HCV patients and correlation of early viral kinetics &

gene expression with ultimate virological response.

Method: Patients with HCV infection commencing standard treatment

were recruited from November 2006. Blood was taken immediately prior

to the commencement of treatment and at 6, 12 & 24 hours.

Results:

Twenty five patients: Male=14,Female=11, all Caucasian, genotype

1=15, genotype 3=10, Median age 40yrs(26-68), Median baseline ALT=122

IU/L(27-621), Median baseline HCV RNA 6.0 log10IU/mL (4.9-6.6).

21 patients 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 (0.1-4.8)]. 4 patients, all genotype 1,

exhibited a slow first phase response <1 log10 IU/ml & ultimately

failed to respond to therapy. One genotype 3 patient cleared virus at

24 hours. The greatest decline occurs between 12-24 hours.

There is a significant difference in the 24 hour decline between

genotypes 1 & 3 (p=0.02). There is also a significant association

between 24 hour log drop and response at 12 weeks (p=0.007).

RT-PCR was performed on PBMCs from 10 patients on a selection of

genes previously associated with interferon therapy.

A significant increase in the expression of OAS 1(p=0.001), TNF

(p=0.04), IRF-7 (p=0.002), Mx-1(p=0.006), STAT 1(p=0.005) & IL 6

(p=0.04) was noted over 24 hours.

There is a significant difference in TNF expression at 24 hours

between responders and nonresponders(p<0.05).There is an overall

trend towards a higher fold change in interferon response gene

expression at both 12 and 24 hours in treatment responders.

Conclusion: These early changes in gene expression and viral kinetics

illustrate treatment effect within the first 24 hours. Correlation of

viral kinetics with treatment outcome can give an indication of

ultimate outcome, allowing modification or withdrawal of treatment at

an early stage.