1311. NK KIR genotype associates with relapse in interferon free HCV therapy
Session: Poster Abstract Session: Biomarkers and Correlates of Protection
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Background: Hepatitis C virus (HCV) is an important public health concern, with 180 million infections worldwide, and no preventative vaccine. Treatment outcome in interferon based HCV therapy is associated with several immune related genes, including interleukin 28B genotype and NK cell killer inhibitory receptor (KIR) 2DS2 genotype. However predictors of treatment outcome with new interferon free, direct acting antiviral (DAA) regimens are unknown. We hypothesized that NK cell KIR genotype may be associated with outcome in novel interferon free HCV therapy.

Methods: Sixty chronic hepatitis C, genotype 1 infected, treatment naive patients were treated with interferon free HCV therapy (sofobuvir and ribavirin) for 24 weeks. In a substudy, genomic DNA was isolated from peripheral blood mononuclear cells in 27 African American patients, 17 with virologic relapse and 10 with sustained viral response (SVR). Patients were genotyped by single specific primer PCR for all 19 known KIR genes, including 5 activating KIR, 2 pseudogenes, and 12 inhibitory KIR.

Results: Four framework KIR genes (2DL4, 3DL2, 3DL3, 2DP1) were observed in all patients, and eight KIR genes (2DL2, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DS1) were found at similar frequency to previously published literature for African American populations. Four activating KIR, namely 2DS2, 2DS3, 2DS4ins and 3DS1  were found more frequently in relapsers than SVR (p< 0.05 for all).  All relapsers had at least one of these KIR genes, and more relapsers had 2 or more of these genes compared to SVR patients (12/17 vs 2/10; p=0.02). 

Conclusion: Four KIR genes are enriched in patients who failed interferon free HCV therapy, three of which have not previously been associated with HCV treatment outcome. KIR genotype is associated with clinical outcome in DAA therapy, suggesting a possible role for NK cells in DAA-associated viral clearance.

Crystal Wang, BS1, Lisa Barrett, MD, PhD2, Anu Osinusi, MD, MPH3,4 and Shyam Kottilil, MD, PhD3, (1)Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, MD, (2)Laboratory of Immunoregulation, Niaid/NIH, Bethesda, MD, (3)NIAID/NIH, Bethesda, MD, (4)Clinical Research Directorate/Cmrp, Saic-Frederick, Inc., Frederick, MD


C. Wang, None

L. Barrett, None

A. Osinusi, None

S. Kottilil, None

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