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Very Early Viral Response to Treatment of Hepatitis C Virus (HCV) with Pegylated Interferon and Ribavirin: the First 24 Hours
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Reported by Jules Levin
DDW, May 17-22, 2008, San Diego
Emma J Devitt, John A Browne, Caroline Walsh, John 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.
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