Dataset Information

Response prediction in chronic hepatitis C by assessment of IP-10 and IL28B-related single nucleotide polymorphisms.

ABSTRACT: BACKGROUND:High baseline levels of IP-10 predict a slower first phase decline in HCV RNA and a poor outcome following interferon/ribavirin therapy in patients with chronic hepatitis C. Several recent studies report that single nucleotide polymorphisms (SNPs) adjacent to IL28B predict spontaneous resolution of HCV infection and outcome of treatment among HCV genotype 1 infected patients. METHODS AND FINDINGS:In the present study, we correlated the occurrence of variants at three such SNPs (rs12979860, rs12980275, and rs8099917) with pretreatment plasma IP-10 and HCV RNA throughout therapy within a phase III treatment trial (HCV-DITTO) involving 253 Caucasian patients. The favorable SNP variants (CC, AA, and TT, respectively) were associated with lower baseline IP-10 (P?=?0.02, P?=?0.01, P?=?0.04) and were less common among HCV genotype 1 infected patients than genotype 2/3 (P<0.0001, P<0.0001, and P?=?0.01). Patients carrying favorable SNP genotypes had higher baseline viral load than those carrying unfavorable variants (P?=?0.0013, P?=?0.029, P?=?0.0004 respectively). Among HCV genotype 1 infected carriers of the favorable C, A, or T alleles, IP-10 below 150 pg/mL significantly predicted a more pronounced reduction of HCV RNA from day 0 to 4 (first phase decline), which translated into increased rates of RVR (62%, 53%, and 39%) and SVR (85%, 76%, and 75% respectively) among homozygous carriers with baseline IP-10 below 150 pg/mL. In multivariate analyses of genotype 1-infected patients, baseline IP-10 and C genotype at rs12979860 independently predicted the first phase viral decline and RVR, which in turn independently predicted SVR. CONCLUSIONS:Concomitant assessment of pretreatment IP-10 and IL28B-related SNPs augments the prediction of the first phase decline in HCV RNA, RVR, and final therapeutic outcome.

SUBMITTER: Lagging M

PROVIDER: S-EPMC3044738 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Response prediction in chronic hepatitis C by assessment of IP-10 and IL28B-related single nucleotide polymorphisms.

Lagging Martin M Askarieh Galia G Negro Francesco F Bibert Stephanie S Söderholm Jonas J Westin Johan J Lindh Magnus M Romero Ana A Missale Gabriele G Ferrari Carlo C Ferrari Carlo C Neumann Avidan U AU Pawlotsky Jean-Michel JM Haagmans Bart L BL Zeuzem Stefan S Bochud Pierre-Yves PY Hellstrand Kristoffer K

PloS one 20110224 2

<h4>Background</h4>High baseline levels of IP-10 predict a slower first phase decline in HCV RNA and a poor outcome following interferon/ribavirin therapy in patients with chronic hepatitis C. Several recent studies report that single nucleotide polymorphisms (SNPs) adjacent to IL28B predict spontaneous resolution of HCV infection and outcome of treatment among HCV genotype 1 infected patients.<h4>Methods and findings</h4>In the present study, we correlated the occurrence of variants at three su ...[more]

PMID: 21390311

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Project description:BACKGROUND:Hepatitis C is a global health problem and represents a major cause of liver disease and socioeconomic burden. Effective antiviral therapy may prevent these complications, but the current treatment for patients with chronic hepatitis C virus (HCV) infection does not produce sustained virologic response. Therefore, identification of the determinants of response to treatment is a high priority. A number of host and viral factors have been associated with treatment outcomes. OBJECTIVES:To assess the associations of single nucleotide polymorphisms (SNP) of the IL28B and sustained virologic response (SVR) of patients with chronic hepatitis C to PEG-interferon/ribavirin therapy. MATERIALS AND METHODS:We searched PubMed, Medline and Cochrane Library, and found 7 eligible papers involved in this study. Then we performed a meta-analysis comparing the SVR rate at SNP of the IL28B in individuals with PEG-interferon/ribavirin therapy. Meanwhile, the SVR rate between different races and HCV genotypes was studied. RESULTS:The sustained virologic response rate was higher in patients with the rs12979860 CC and rs8099917 TT alleles in the IL28B SNP, comparing with the rs12979860 CT, or TT and rs8099917 TG or GG. Furthermore, a higher SVR was observed in the Caucasians than in Afro-Americans (OR = 3.85, 95% CI: 3.06-4.83); the percentage of rs12979860 TT genotype was lower in Caucasians (OR = 0.25, 95% CI: 0.20-0.31) and the percentage of rs12979860 CC genotype was higher in Caucasians than that of Afro-Americans (OR = 3.45, 95% CI = 2.68-4.44). Between different HCV genotypes, the SVR was much lower in those with HCV genotype 1 than those with genotype 2/3 (OR = 0.16, 95% CI: 0.11-0.24). CONCLUSIONS:IL28B is significantly associated with response to PEG-interferon/ribavirin therapy of patients with chronic HCV infection. Both the rs12979860 and rs8099917 alleles could be used as independent predictors of the treatment response. The rs12979860 allele in particular, is more important from our study. The polymorphism even explains part the difference in response rate between different ethnic groups and HCV genotypes.

Dataset Information

Response prediction in chronic hepatitis C by assessment of IP-10 and IL28B-related single nucleotide polymorphisms.

Publications

Response prediction in chronic hepatitis C by assessment of IP-10 and IL28B-related single nucleotide polymorphisms.

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