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Optimum ribavirin exposure overcomes racial disparity in Hep C genotype 1 treatment

Optimum ribavirin exposure overcomes racial disparity in efficacy of peginterferon and ribavirin treatment for Hepatitis C genotype 1, reports the latest issue of the American Journal of Gastroenterology.

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Peginterferon and ribavirin treatment is less effective for hepatitis C virus genotype 1 infections in African Americans compared with Caucasian Americans.
 
Host genetic variability near the interleukin-28B gene locus is partly responsible.
 
Dr Runyan Jin and colleagues from Maryland, USA investigated the relationship between ribavirin drug exposure and week 24 and 72 sustained virologic response.
 
The team examined responses in 71 African Americans, and 74 Caucasian Americans with HCV genotype 1 who received 90% or more of the prescribed peginterferon and weight-based ribavirin from week 1 to 24.
 
Ribavirin plasma levels were measured at weeks 1, 2, 4, 8, 12 and 24.
African Americans had lower ribavirin exposure from week 1 to 12
American Journal of Gastroenterology
 
Ribavirin area under the concentration vs time curve was calculated using the linear trapezoidal rule.
 
The research team found that Caucasian Americans compared with African Americans had a lower week 24 and week 72 sustained virologic response response rates.
 
African Americans also had significantly lower ribavirin exposure from week 1 to 12.
 
The team found that ribavirin exposures of 4,065 and 4,480 ng/ml/day in the first
week were thresholds for WK24VR and sustained virological responses.
 
African Americans were less likely to have a threshold ribavirin AUC0-7 level than Caucasian Americans.
 
The researchers noted that there were no significant racial differences in WK24VR, and rates in patients who met the ribavirin AUC0-7 thresholds.
 
Ribavirin AUC0-7 predicted WK24VR and sustained virological response independently of IL28B single-nucleotide polymorphism rs12979860 genotype.
 
The team noted that achieving threshold AUC0-7 levels increased response rates primarily in AA with the less favorable non-C/C genotypes.
 
Dr Runyan's team concluded that "Standard weight-based dosing leads to suboptimal ribavirin exposure in African Americans and contributes to the racial disparity in peginterferon and ribavirin treatment efficacy for HCV genotype 1."

Am J Gastroenterol 2012; 107:1675–1683
03 December 2012

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