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Pretreatment prediction of the outcome of response-guided peginterferon-α and ribavirin therapy for chronic hepatitis C.

Masaki N, Sugiyama M, Shimada N, Tanaka Y, Nakamuta M, Izumi N, Watanabe S, Tsubota A, Komatsu M, Masaki T, Enomoto N, Yoneda M, Murata K, Ito K, Koike K, Mizokami M - J. Gastroenterol. Hepatol. (2014)

Bottom Line: The accuracy for predicting virological outcomes of peginterferon-α and ribavirin therapy in patients with chronic hepatitis C is limited to approximately 80%, even with IL28B genotyping.Our in vitro study revealed that the numbers of (TA) dinucleotide repeats [(TA)n] of rs72258881, which is located in the promoter region of IL28B gene, might regulate IL28B transcription.We aimed to evaluate the usefulness of these host factors for predicting virological outcomes of this therapy in response-guided clinical settings.

View Article: PubMed Central - PubMed

Affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.

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Related in: MedlinePlus

Genotype of rs8099917, (TA) dinucleotide repeat [(TA)n] of rs72258881 and virological response. (a) Hepatitis C virus (HCV) RNA disappearance rate. Serum HCV RNA disappeared significantly earlier in patients with TT genotype than in those with TG/GG genotypes. *P < 0.05, **P < 0.001. The abbreviation used was: EOT, end of treatment; HCV, hepatitis C virus; w, weeks. , TT genotype; , TG/GG genotype. (b) Distributions of (TA)n in this cohort. The most frequent (TA)n was 12 (n = 147: 68.4%). In 67 patients (31.2%), the numbers were more than 12. (c) The incidences of virological response (VR) in four groups stratified by rs8099917 genotype and (TA)n. The longer (TA)n might favor virological responses to PEGylated interferon-α and ribavirin, regardless of the IL28B genotype.
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fig03: Genotype of rs8099917, (TA) dinucleotide repeat [(TA)n] of rs72258881 and virological response. (a) Hepatitis C virus (HCV) RNA disappearance rate. Serum HCV RNA disappeared significantly earlier in patients with TT genotype than in those with TG/GG genotypes. *P < 0.05, **P < 0.001. The abbreviation used was: EOT, end of treatment; HCV, hepatitis C virus; w, weeks. , TT genotype; , TG/GG genotype. (b) Distributions of (TA)n in this cohort. The most frequent (TA)n was 12 (n = 147: 68.4%). In 67 patients (31.2%), the numbers were more than 12. (c) The incidences of virological response (VR) in four groups stratified by rs8099917 genotype and (TA)n. The longer (TA)n might favor virological responses to PEGylated interferon-α and ribavirin, regardless of the IL28B genotype.

Mentions: Intent-to-treat analysis of the entire cohort indicated SVR, TVR, and NVR rates of 49.3%, 12.6%, and 32.1%, respectively. As shown in Figure 3a, serum HCV RNA disappeared significantly earlier in patients with TT genotype than in those with either of the TG or GG genotype. Assessment of the usefulness of the rs8099917 non-TT genotype to predict NVR among 202 patients in whom the final virological outcome could be determined indicate a sensitivity of 63.8% (44/[44 + 25]); specificity of 88.0% (117/[117 + 16]); positive predictive value of 73.3% (44/[44 + 16]); negative predictive value of 82.4% (117/[25 + 117]), and an accuracy of 79.7% ([44 + 117]/202).


Pretreatment prediction of the outcome of response-guided peginterferon-α and ribavirin therapy for chronic hepatitis C.

Masaki N, Sugiyama M, Shimada N, Tanaka Y, Nakamuta M, Izumi N, Watanabe S, Tsubota A, Komatsu M, Masaki T, Enomoto N, Yoneda M, Murata K, Ito K, Koike K, Mizokami M - J. Gastroenterol. Hepatol. (2014)

Genotype of rs8099917, (TA) dinucleotide repeat [(TA)n] of rs72258881 and virological response. (a) Hepatitis C virus (HCV) RNA disappearance rate. Serum HCV RNA disappeared significantly earlier in patients with TT genotype than in those with TG/GG genotypes. *P < 0.05, **P < 0.001. The abbreviation used was: EOT, end of treatment; HCV, hepatitis C virus; w, weeks. , TT genotype; , TG/GG genotype. (b) Distributions of (TA)n in this cohort. The most frequent (TA)n was 12 (n = 147: 68.4%). In 67 patients (31.2%), the numbers were more than 12. (c) The incidences of virological response (VR) in four groups stratified by rs8099917 genotype and (TA)n. The longer (TA)n might favor virological responses to PEGylated interferon-α and ribavirin, regardless of the IL28B genotype.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263356&req=5

fig03: Genotype of rs8099917, (TA) dinucleotide repeat [(TA)n] of rs72258881 and virological response. (a) Hepatitis C virus (HCV) RNA disappearance rate. Serum HCV RNA disappeared significantly earlier in patients with TT genotype than in those with TG/GG genotypes. *P < 0.05, **P < 0.001. The abbreviation used was: EOT, end of treatment; HCV, hepatitis C virus; w, weeks. , TT genotype; , TG/GG genotype. (b) Distributions of (TA)n in this cohort. The most frequent (TA)n was 12 (n = 147: 68.4%). In 67 patients (31.2%), the numbers were more than 12. (c) The incidences of virological response (VR) in four groups stratified by rs8099917 genotype and (TA)n. The longer (TA)n might favor virological responses to PEGylated interferon-α and ribavirin, regardless of the IL28B genotype.
Mentions: Intent-to-treat analysis of the entire cohort indicated SVR, TVR, and NVR rates of 49.3%, 12.6%, and 32.1%, respectively. As shown in Figure 3a, serum HCV RNA disappeared significantly earlier in patients with TT genotype than in those with either of the TG or GG genotype. Assessment of the usefulness of the rs8099917 non-TT genotype to predict NVR among 202 patients in whom the final virological outcome could be determined indicate a sensitivity of 63.8% (44/[44 + 25]); specificity of 88.0% (117/[117 + 16]); positive predictive value of 73.3% (44/[44 + 16]); negative predictive value of 82.4% (117/[25 + 117]), and an accuracy of 79.7% ([44 + 117]/202).

Bottom Line: The accuracy for predicting virological outcomes of peginterferon-α and ribavirin therapy in patients with chronic hepatitis C is limited to approximately 80%, even with IL28B genotyping.Our in vitro study revealed that the numbers of (TA) dinucleotide repeats [(TA)n] of rs72258881, which is located in the promoter region of IL28B gene, might regulate IL28B transcription.We aimed to evaluate the usefulness of these host factors for predicting virological outcomes of this therapy in response-guided clinical settings.

View Article: PubMed Central - PubMed

Affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.

Show MeSH
Related in: MedlinePlus