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Predictors of response to 24-week telaprevir-based triple therapy for treatment-naïve genotype 1b chronic hepatitis C patients.

Abe H, Tsubota A, Shimada N, Atsukawa M, Kato K, Takaguchi K, Asano T, Chuganji Y, Sakamoto C, Toyoda H, Kumada T, Ide T, Sata M, Aizawa Y - Gastroenterol Res Pract (2014)

Bottom Line: The baseline and treatment-related factors potentially associated with SVR were determined by multivariate logistic regression analysis.Achievement of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 of treatment, was identified as an after-starting-treatment predictor (P = 2.47 × 10(-5)).However, neither a substitution in core aa 70 nor the number of substitutions in the ISDR affected treatment outcome.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-0062, Japan.

ABSTRACT
We evaluated the genetic variation in rs8099917, substitutions in core amino acid (aa) 70, and the number of aa substitutions in the interferon sensitivity-determining region (ISDR) on the prediction of sustained virological response (SVR) in treatment-naïve hepatitis C virus (HCV) genotype 1b (G1b) patients. This multicenter study involved 150 Asian treatment-naïve patients infected with HCV G1b who received 12 weeks of telaprevir in combination with 24 weeks of peginterferon-α-2b and ribavirin. The baseline and treatment-related factors potentially associated with SVR were determined by multivariate logistic regression analysis. Virological response was analyzed on an intent-to-treat basis. Cessation of the therapy due to adverse effects occurred in only 2 patients, who discontinued the trial at 10 weeks and at 2 weeks due to cerebral infarction and renal impairment, respectively. Among the 150 patients in whom the final virological response was determined, only genotype TT in rs8099917 was identified as a pretreatment predictor (P = 7.38 × 10(-4)). Achievement of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 of treatment, was identified as an after-starting-treatment predictor (P = 2.47 × 10(-5)). However, neither a substitution in core aa 70 nor the number of substitutions in the ISDR affected treatment outcome.

No MeSH data available.


Related in: MedlinePlus

According to the genetic variation in rs8099917, near the IL28B gene, a significantly higher proportion of patients with the TT genotype showed a sustained virological response (SVR) than did patients with the TG or GG genotype. In contrast, based on the amino acid substitutions in the core region (amino acid 70) and interferon sensitivity-determining region (ISDR), there was no significant association between the SVR rate and these substitutions, irrespective of the rs8099917 genotype. Furthermore, the SVR rate was 98.9% in patients with the rs8099917 TT genotype who achieved rapid virological response (RVR), whereas the SVR rate was 23.1% among patients with the TG or GG rs8099917 genotype who did not achieve RVR.
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Related In: Results  -  Collection


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fig1: According to the genetic variation in rs8099917, near the IL28B gene, a significantly higher proportion of patients with the TT genotype showed a sustained virological response (SVR) than did patients with the TG or GG genotype. In contrast, based on the amino acid substitutions in the core region (amino acid 70) and interferon sensitivity-determining region (ISDR), there was no significant association between the SVR rate and these substitutions, irrespective of the rs8099917 genotype. Furthermore, the SVR rate was 98.9% in patients with the rs8099917 TT genotype who achieved rapid virological response (RVR), whereas the SVR rate was 23.1% among patients with the TG or GG rs8099917 genotype who did not achieve RVR.

Mentions: The rates of SVR in these patients are illustrated in Figure 1. Neither the substitution in aa 70 in the HCV core region nor the number of aa substitutions in the ISDR impacted the prediction of SVR, regardless of the rs8099917 genotype.


Predictors of response to 24-week telaprevir-based triple therapy for treatment-naïve genotype 1b chronic hepatitis C patients.

Abe H, Tsubota A, Shimada N, Atsukawa M, Kato K, Takaguchi K, Asano T, Chuganji Y, Sakamoto C, Toyoda H, Kumada T, Ide T, Sata M, Aizawa Y - Gastroenterol Res Pract (2014)

According to the genetic variation in rs8099917, near the IL28B gene, a significantly higher proportion of patients with the TT genotype showed a sustained virological response (SVR) than did patients with the TG or GG genotype. In contrast, based on the amino acid substitutions in the core region (amino acid 70) and interferon sensitivity-determining region (ISDR), there was no significant association between the SVR rate and these substitutions, irrespective of the rs8099917 genotype. Furthermore, the SVR rate was 98.9% in patients with the rs8099917 TT genotype who achieved rapid virological response (RVR), whereas the SVR rate was 23.1% among patients with the TG or GG rs8099917 genotype who did not achieve RVR.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4150495&req=5

fig1: According to the genetic variation in rs8099917, near the IL28B gene, a significantly higher proportion of patients with the TT genotype showed a sustained virological response (SVR) than did patients with the TG or GG genotype. In contrast, based on the amino acid substitutions in the core region (amino acid 70) and interferon sensitivity-determining region (ISDR), there was no significant association between the SVR rate and these substitutions, irrespective of the rs8099917 genotype. Furthermore, the SVR rate was 98.9% in patients with the rs8099917 TT genotype who achieved rapid virological response (RVR), whereas the SVR rate was 23.1% among patients with the TG or GG rs8099917 genotype who did not achieve RVR.
Mentions: The rates of SVR in these patients are illustrated in Figure 1. Neither the substitution in aa 70 in the HCV core region nor the number of aa substitutions in the ISDR impacted the prediction of SVR, regardless of the rs8099917 genotype.

Bottom Line: The baseline and treatment-related factors potentially associated with SVR were determined by multivariate logistic regression analysis.Achievement of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 of treatment, was identified as an after-starting-treatment predictor (P = 2.47 × 10(-5)).However, neither a substitution in core aa 70 nor the number of substitutions in the ISDR affected treatment outcome.

View Article: PubMed Central - PubMed

Affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-0062, Japan.

ABSTRACT
We evaluated the genetic variation in rs8099917, substitutions in core amino acid (aa) 70, and the number of aa substitutions in the interferon sensitivity-determining region (ISDR) on the prediction of sustained virological response (SVR) in treatment-naïve hepatitis C virus (HCV) genotype 1b (G1b) patients. This multicenter study involved 150 Asian treatment-naïve patients infected with HCV G1b who received 12 weeks of telaprevir in combination with 24 weeks of peginterferon-α-2b and ribavirin. The baseline and treatment-related factors potentially associated with SVR were determined by multivariate logistic regression analysis. Virological response was analyzed on an intent-to-treat basis. Cessation of the therapy due to adverse effects occurred in only 2 patients, who discontinued the trial at 10 weeks and at 2 weeks due to cerebral infarction and renal impairment, respectively. Among the 150 patients in whom the final virological response was determined, only genotype TT in rs8099917 was identified as a pretreatment predictor (P = 7.38 × 10(-4)). Achievement of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 of treatment, was identified as an after-starting-treatment predictor (P = 2.47 × 10(-5)). However, neither a substitution in core aa 70 nor the number of substitutions in the ISDR affected treatment outcome.

No MeSH data available.


Related in: MedlinePlus