High ability to predict the treatment outcome of peginterferon and ribavirin combination therapy based on the reduction in HCV RNA levels at 4 weeks after starting therapy and amino acid substitutions in the hepatitis C virus in patients infected with HCV genotype 1b

Toyoda, Hidenori; Kumada, Takashi; Kiriyama, Seiki; Tanikawa, Makoto; Hisanaga, Yasuhiro; Kanamori, Akira; Tada, Toshifumi; Arakawa, Takahiro; Fujimori, Masashi; Niinomi, Takuro; Ando, Naoto; Yasuda, Satoshi; Sakai, Keisuke; Kimura, Jun

doi:10.1007/s00535-010-0328-z

Cited by 10 publications

(8 citation statements)

References 39 publications

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“…The percentage is comparable to that reported by Marcellin et al [5] and in our previous study [6]. Multivariate analysis indicated that factors associated with this failure include female sex, higher pretreatment HCV RNA levels, and lower baseline ALT activity.…”

Section: Discussionsupporting

confidence: 78%

“…In addition to RVR, the degree of reduction in serum HCV RNA levels 4 weeks after starting therapy is useful; a 3.0 log 10 or more reduction in HCV RNA levels at 4 weeks indicates a high likelihood of achieving SVR even without RVR. Previous studies by Marcellin et al [5] and our group [6] showed that a ≥3.0 log 10 reduction at 4 weeks is associated with a high likelihood of both achieving a complete early virologic response (EVR), i.e. undetectable serum HCV RNA 12 weeks after starting therapy, and SVR.…”

Section: Introductionmentioning

confidence: 99%

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Characteristics and Outcomes of HCV Genotype-1-Infected Patients Treated with Peginterferon and Ribavirin Combination Therapy with Discordant HCV Responses 4 and 12 Weeks after Starting Therapy

et al. 2014

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Objective: Some patients with chronic hepatitis C virus (HCV) infection fail to achieve complete early virologic response (EVR) despite a marked decrease in HCV RNA at 4 weeks. We investigated the characteristics and final treatment outcomes of this patient subpopulation. Methods: A total of 516 patients with HCV genotype 1 were enrolled. Background characteristics and final outcomes were compared between patients who achieved complete EVR and those who did not among patients whose HCV RNA levels decreased 3.0 log₁₀ or more at 4 weeks. Results: 78 of 334 patients (23.4%) with a ≥3.0 log₁₀ reduction in HCV RNA levels at 4 weeks failed to achieve complete EVR. Female sex, higher pretreatment HCV RNA levels and lower baseline alanine aminotransferase (ALT) activity were independently associated with failure of complete EVR. The rate of sustained virologic response (SVR) in patients without complete EVR was 47.4%, significantly lower than that in patients with complete EVR (89.7%, p < 0.0001). Conclusions: Female patients, patients with higher pretreatment HCV RNA levels and patients with lower baseline ALT have a high likelihood of failure of complete EVR even when they had a ≥3 log₁₀ reduction of HCV RNA at 4 weeks, resulting in a significantly lower SVR rate.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Characteristics and Outcomes of HCV Genotype-1-Infected Patients Treated with Peginterferon and Ribavirin Combination Therapy with Discordant HCV Responses 4 and 12 Weeks after Starting Therapy

et al. 2014

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“…In addition, several recent studies reported the predictive value of the degree of reduction in serum HCV RNA levels at 4 weeks after starting therapy [Yu et al, 2007;Huang et al, 2010;Toyoda et al, 2011]. Therefore, the viral dynamics of HCV at 4 as well as 12 weeks after starting therapy is important for response-guided therapy.…”

Section: Discussionmentioning

confidence: 95%

“…A rapid virologic response, in which serum HCV RNA is undetectable at 4 weeks after starting therapy, has been the strongest predictive factor of a sustained virologic response reportedly [Martinez-Bauer et al, 2006;Poordad et al, 2008;de Segadas-Soares et al, 2009;Martinot-Peignoux et al, 2009]. In addition, the predictive value of reduced serum HCV RNA levels at 4 weeks after starting therapy has been clarified further, and a !3 log 10 reduction in HCV RNA levels at 4 weeks after starting therapy has high predictive value that a patient will achieve a sustained virologic response as a final outcome, even in the absence of a rapid virologic response [Toyoda et al, 2011].…”

Section: Introductionmentioning

confidence: 99%

Predictive value of early viral dynamics during peginterferon and ribavirin combination therapy based on genetic polymorphisms near the IL28B gene in patients infected with HCV genotype 1b

Toyoda

Kumada

Tada

et al. 2011

Journal of Medical Virology

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A study was carried out to determine whether early viral dynamics retain prediction of the outcome of peginterferon (PEG-IFN) and ribavirin combination therapy based on different genetic polymorphisms near the IL28B gene, the strongest baseline predictor of response to this therapy. A total of 272 patients infected with hepatitis C virus (HCV) genotype 1b were grouped according to genetic polymorphisms near the IL28B gene (rs8099917). The ability of reduced HCV RNA levels at 4 and 12 weeks after starting therapy to predict a sustained virologic response was evaluated based on these genotypes. Among patients with the TT genotype for rs8099917 (associated with a favorable response), the rates of sustained virologic response were higher in patients with a ≥3 log(10) reduction in serum HCV RNA levels at 4 weeks after starting therapy (P < 0.0001). In contrast, among patients with the TG/GG genotype (associated with an unfavorable response), there were no differences in this rate based on the reduction in HCV RNA levels at 4 weeks. Early viral dynamics at 4 weeks after starting therapy retains its predictive value for sustained virologic response in patients with the TT genotype for rs8099917, but not in patients with the TG/GG genotype. Patients who are likely to achieve sustained virologic response despite unfavorable TG/GG genotype cannot be identified based on early viral dynamics during therapy. In contrast, lack of early virologic response at 12 weeks retains a strong predictive value for the failure of sustained virologic response regardless of IL28B polymorphisms, which remains useful as a factor to stop therapy.

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“…RVR was also significantly related to SVR in the previously relapsed group. Patients achieving RVR have a high likelihood of achieving SVR by PEG-IFN/RBV combination therapy [26,27]. Our study also suggested that achievement of RVR is essential for achieving SVR.…”

Section: Discussionmentioning

confidence: 48%

Outcome of Double-Filtration Plasmapheresis plus Interferon Treatment in Nonresponders to Pegylated Interferon plus Ribavirin Combination Therapy

Sugimoto¹,

Kim

El-Shamy³

et al. 2013

Dig Dis

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Objectives: We assessed the outcome of double-filtration plasmapheresis (DFPP) combined with pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy in patients infected with hepatitis C virus (HCV)-1b whose HCV had not disappeared during PEG-IFN/RBV combination therapy, or who had relapsed after the end of the therapy. Additionally, we investigated factors predictive of sustained virological response (SVR), including host and viral genetic factors, to DFPP plus IFN/RBV therapy. Methods: A total of 40 patients infected with HCV-1b whose HCV virus had not been eradicated by previous PEG-IFN/RBV therapy were enrolled for treatment by DFPP plus IFN/RBV. Rapid virological response (RVR) and SVR were assessed, and pretreatment factors associated with SVR - the interleukin (IL)28B gene, the IFN/RBV resistance-determining region (IRRDR) and the IFN sensitivity-determining region (ISDR) - were analyzed. Results: Of the 40 patients, 9 (23%) achieved RVR and 10 (25%) achieved SVR. The significant factors associated with SVR were IL28B major and RVR,as assessed by multivariate analysis (p = 0.0182, p = 0.0005). Conclusion: Patients whose HCV is not eradicated by previous PEG-IFN/RBV would be good candidates for combined DFPP and IFN/RBV retreatment provided they demonstrate IL28B major and have achieved RVR.

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High ability to predict the treatment outcome of peginterferon and ribavirin combination therapy based on the reduction in HCV RNA levels at 4 weeks after starting therapy and amino acid substitutions in the hepatitis C virus in patients infected with HCV genotype 1b

Cited by 10 publications

References 39 publications

Characteristics and Outcomes of HCV Genotype-1-Infected Patients Treated with Peginterferon and Ribavirin Combination Therapy with Discordant HCV Responses 4 and 12 Weeks after Starting Therapy

Characteristics and Outcomes of HCV Genotype-1-Infected Patients Treated with Peginterferon and Ribavirin Combination Therapy with Discordant HCV Responses 4 and 12 Weeks after Starting Therapy

Predictive value of early viral dynamics during peginterferon and ribavirin combination therapy based on genetic polymorphisms near the IL28B gene in patients infected with HCV genotype 1b

Outcome of Double-Filtration Plasmapheresis plus Interferon Treatment in Nonresponders to Pegylated Interferon plus Ribavirin Combination Therapy

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