Short‐term prolongation of pegylated interferon and ribavirin therapy for genotype 1b chronic hepatitis C patients with early viral response

Hepatology Research (Impact Factor: 2.74). 05/2009; 39(8):753 - 759. DOI: 10.1111/j.1872-034X.2009.00523.x


Aim: We tailored extended treatments using pegylated interferon (PEG IFN) and ribavirin (RBV) to viral responses after initiation of therapy and investigated the efficacy and safety of its therapy for chronic hepatitis C (CHC) patients.
Methods: Eighty-two genotype 1b CHC patients were enrolled in the present study. All patients received PEG IFN-α-2b and weight-based RBV therapy. We defined a viral response in which serum HCV-RNA is undetectable at week 4 as rapid viral response (RVR), detectable at week 4 and undetectable by week 12 as early viral response (EVR), and detectable at week 12 and undetectable by week 24 as late viral response (LVR). We set the treatment duration depending on viral response; 48 weeks for RVR patients and 72 weeks for LVR. Furthermore, EVR patients received a short-term extension of treatment duration to 52–60 weeks. We prospectively investigated sustained viral response (SVR) rates of these groups.
Results: Overall SVR rate for the total patient group was 57.3%. SVR rates of the RVR, EVR and LVR patients were 100%, 80.5% and 40.0%, respectively. Nine patients could not complete this treatment protocol. Baseline platelet count and mutation in the interferon sensitivity-determining region of NS5A were significant independent predictors of SVR, and amino acid substitution of the core region was a significant independent predictor of non-viral response by multivariate logistic regression analyses.
Conclusion: The results indicate that short-treatment extension of PEG IFN plus RBV treatment protocols in EVR patients can improve overall SVR rates.

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    ABSTRACT: We investigated "Response-guided therapy" 48 weeks vs. 72 weeks in 250 Japanese chronic hepatitis C patients infected with genotype 1b and high viral load to peginterferon (Peg-IFN) α-2b plus ribavirin (RBV). SVR rate was 100% of patients with RVR. Although patients with cEVR did not significantly improve SVR rate with extended treatment to 72 weeks, patients with pEVR were significantly improved with extended treatment (8.0% vs. 59.6%, p<0.0001). In patients with non-RVR except for NVR, extended treatment to 72 weeks significantly improved SVR rate compared with 48-week treatment (57.8% vs. 72.4%, p = 0.0413). Multivariate analysis identified low-density lipoprotein cholesterol (≥86 mg/dL), total dose of RBV per body weight (≥3 g/kg), cEVR, periods to the intial HCV-RNA negative to 20 weeks as significant determinants of SVR. When non-RVR cases with HCV-RNA reduction during 0-4 weeks less than 2 Log 10 IU/mL and that achieved LVR, total dose of RBV per body weight more than 3 g/kg and extended treatment to 72 weeks may increase SVR rate. Response-guided therapy is useful strategy in the treatment for chronic hepatitis C with genotype 1b and high viral load.
    Kanzo 01/2009; 50(12):687-702. DOI:10.2957/kanzo.50.687
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    ABSTRACT: Pegylated interferon combined with ribavirin treatment for 48 weeks is commonly used for chronic hepatitis C patients with genotype 1 and high viral load Additionally, the 2010 guideline by the Study Group for the Standardization of Treatment of Viral Hepatitis Including Cirrhosis, under the auspice of the Ministry of Health Labor and Welfare of Japan newly recommends 72 weeks treatment for elder female or advanced stage patients, whose HCV RNA turned negative at between 9 and 36 weeks by real-time PCR. In this study, we investigated the efficacy of 60 weeks treatment in patients, whose HCV RNA turned negative at 12 weeks. SVR was achieved in 29 out of 30 cases. Among those cases, 8 females were over 50 years old, and 6 cases were advanced stage. Sixty weeks treatment is considered satisfactory for patients whose HCV RNA turned negative at 12 weeks.
    Kanzo 01/2010; 51(10):589-590. DOI:10.2957/kanzo.51.589
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    ABSTRACT: Clinical trials provided conflicting results about whether extended duration of treatment with pegylated interferon-alfa (pegIFN-alfa) and ribavirin (more than 48 weeks) improves rates of sustained virologic response (SVR) in patients infected with hepatitis C virus (HCV) genotype 1 and slow virologic response. We performed a meta-analysis to determine the overall impact of extended treatment, compared with standard treatment, on virologic response rates in these patients. We performed a literature search to identify randomized controlled trials (RCTs) that included monoinfected, treatment-naive patients infected with HCV genotype 1; data were compared between slow responding patients treated with pegIFN-alfa-2a/b plus ribavirin for 48 weeks and those that received extended treatment (as much as 72 weeks). End points included SVR rates, end-of-treatment (EOT) response and relapse rates; they were calculated according to the DerSimonian-Laird estimate. Six RCTs assessed the benefits of extended treatment with pegIFN-alfa-2a/b and ribavirin in treatment-naive patients with HCV genotype 1 that were slow responders (n = 669). The extended treatment significantly improved SVR rates in slow responders, compared with the standard of care (14.7% increase in overall SVR; 95% confidence interval, 4%-25.5%; P = .0072). Rates of viral relapse were significantly reduced by extended treatment, but EOT response rates were similar. The frequency of voluntary treatment discontinuation, but not of serious adverse events, was significantly increased by extended therapy. Extending the duration of treatment with pegIFN-alfa-2a/b and ribavirin in patients with HCV genotype 1 and a slow response to therapy improves the rate of SVR.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 10/2010; 8(10):884-90. DOI:10.1016/j.cgh.2010.06.019 · 7.90 Impact Factor
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