Yu ML, Dai CY, Huang JF, Chiu CF, Yang YH, Hou NJ, et al. Rapid virological response and treatment duration for chronic hepatitis C genotype 1 patients: a randomized trial. Hepatology 2008;47:1884-1893

Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Hepatology (Impact Factor: 11.06). 06/2008; 47(6):1884-93. DOI: 10.1002/hep.22319
Source: PubMed


Recommended treatment for hepatitis C virus genotype 1 (HCV-1) patients is peginterferon plus ribavirin for 48 weeks. We assessed whether treatment duration of 24 weeks is as effective as standard treatment in HCV-1 patients with a rapid virological response (RVR; seronegative for hepatitis C virus [HCV] RNA at 4 weeks). Two hundred HCV-1 patients were randomized (1:1) to either 24 or 48 weeks of peginterferon-alpha-2a (180 microg/week) and ribavirin (1000-1200 mg/day) with a 24-week follow-up. The primary endpoint was a sustained virological response (SVR; seronegative for HCV RNA at 24-week follow-up). Overall, the 48-week arm had a significantly higher SVR rate (79%) than the 24-week arm (59%, P = 0.002). For 87 (43.5%) patients with an RVR, the 24-week arm had a lower SVR rate [88.9%; 95% confidence interval (CI): 80%-98%] than the 48-week arm (100%, P = 0.056). For 52 patients with low baseline viremia (<400,000 IU/mL) and an RVR, the 24-week arm had rates (CI) of relapse and SVR of 3.6% (-3%-11%) and 96.4% (89%-103%), respectively, which were comparable to those of the 48-week arm (0% and 100%) with difference (CI) of 3.6% (-7.2%-6.6%) and -3.6% (-14.3% to -0.6%), respectively. Multivariate analysis in all patients showed that RVR was the strongest independent factor associated with an SVR, followed by treatment duration, mean weight-based exposure of ribavirin, and baseline viral load. CONCLUSION: HCV-1 patients derive a significantly better SVR from 48 weeks versus 24 weeks of peginterferon/ribavirin even if they attain an RVR. Both 24 and 48 weeks of therapy can achieve high SVR rates (>96%) in HCV-1 patients with low viral loads and an RVR.

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Available from: Ming-Lung Yu
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    • "For treatment of HCV genotype 2, the duration of combination therapy has been extended to raise the sustained virological response rate in patients who do not show a rapid virological response (serum HCV RNA disappearance after 4 weeks of therapy) [Sato et al., 2012], while several trials to shorten the treatment duration have been carried out in patients who had favorable host and viral characteristics and who achieved rapid virological response with combination therapy [Toyoda et al., 2009]. The aim of shortening the duration of therapy is mainly to reduce the expense and the adverse effects of treatment [Yu et al., 2008; Berg et al., 2009]. The results of some randomized, controlled studies suggested that patients with HCV genotype 2 who achieved rapid virological response had a very high, sustained virological response rate after 12 or 16 weeks of Peg- IFN-plus-ribavirin combination therapy [Mangia et al., 2005; von Wagner et al., 2005]. "
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    ABSTRACT: This study aimed to determine the most suitable duration of pegylated-interferon (Peg-IFN)-plus-ribavirin combination therapy in patients infected with hepatitis C virus (HCV) genotype 2 who had not achieved rapid virological response (serum HCV RNA disappearance after 4 weeks of therapy). HCV genotype 2 patients (n = 182) with a high viral load received >80% of the standard Peg-IFN-plus-ribavirin dose for at least 24 weeks, and their final virological responses were studied. Patients were classified into "rapid virological response" and "non-rapid virological response" groups. The non-rapid virological response group was further divided into a "virological response at 8 weeks" (serum HCV RNA disappearance after 8 weeks of therapy) and a "non-virological response at 8 weeks" group. Factors related to rapid virological response and optimal therapy duration in the non-rapid virological response group were evaluated. Multivariate logistic regression analysis showed that subtype HCV genotype 2a (P = 0.0015) and low concentration of pretreatment serum HCV RNA (P = 0.0058) were independent factors in a rapid virological response. In the virological response at 8 weeks group, the sustained virological response rate after 24 weeks of therapy was significantly lower than after 36 weeks (P = 0.044) or after 48 weeks (P = 0.006), and was similar for 36- and 48-weeks. The cost for achieving (CAS) one sustained virological response was lowest with 36-week therapy. Prolongation of Peg-IFN-plus-ribavirin combination therapy to 36 weeks is suitable for achieving virological response at 8 weeks, given the high, sustained virological response rate and cost benefit. J. Med. Virol. © 2013 Wiley Periodicals, Inc.
    Full-text · Article · Sep 2013 · Journal of Medical Virology
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    • "For the treatment of genotype 1 chronic hepatitis C, proposed treatment strategies include shortening of treatment period in patients with RVR and extension of treatment period in patients with a delayed response to the initial treatment as judged at week 12 [9–17]. For the treatment of genotype 1 high virus titer chronic hepatitis C, shortening of the treatment period may not be recommended even if RVR is achieved because of a possible reduction in the SVR rate, whereas extension of the treatment period to 72 weeks has been reported to increase the SVR rate in patients showing a delayed response to the initial treatment [12, 14–18]. In addition, combined use of HMG-CoA reductase inhibitors and IFN has been shown to enhance the antiviral effects in a synergistic manner [19]. "
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    ABSTRACT: Background We conducted a multicenter randomized clinical trial to determine the optimal treatment strategy against chronic hepatitis C virus (HCV) with genotype 1b and a high viral load (G1b/high). Methods The study subjects included 153 patients with G1b/high. Patients were initially treated with PEG-IFNα-2a alone and then randomly assigned to receive different treatment regimens. Ribavirin (RBV) was administered to all patients with HCV RNA at week 4. Patients negative for HCV RNA at week 4 were randomly assigned to receive PEG-IFNα-2a (group A) or PEG-IFNα-2a/RBV (group B). Patients who showed HCV RNA at week 4 but were negative at week 12 were randomly assigned to receive weekly PEG-IFNα-2a (group C) or biweekly therapy (group D). Patients who showed HCV RNA at week 12 but were negative at week 24 were randomly assigned to receive PEG-IFNα-2a/RBV (group E) or PEG-IFNα-2a/RBV/fluvastatin (group F). Results Overall, the rate of sustained virological response (SVR) was 46 % (70/153). The total SVR rate in the group (A, D, and F) of response-guided therapy was significantly higher than that in the group (B, C, and E) of conventional therapy [70 % (38/54) versus 52 % (32/61), p = 0.049]. Although IL28-B polymorphism and Core 70 mutation were significantly associated with efficacy, patients with rapid virological response (RVR) and complete early virological response (cEVR) achieved high SVR rates regardless of their status of IL-28B polymorphism and Core 70 mutation. Conclusion In addition to knowing the IL-28B polymorphism and Core 70 mutation status, understanding the likelihood of virological response during treatment is critical in determining the appropriate treatment strategy.
    Full-text · Article · Mar 2013 · Journal of Gastroenterology
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    • "In previous studies [7], [32], [33] and ours focusing on GT1 patients [27], the genetic variants of IL28B SNP had a more significant impact on SVR in patients without RVR rather than those with RVR. However, in the present studies, the genetic variants of IL28B SNP did not influence the treatment outcome in both the RVR group and non-RVR group in GT2 patients using propensity score matching analysis. "
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    ABSTRACT: Background & Aims A combination of pegylated interferon-alpha and ribavirin (PR) is the standard therapy for patients with chronic hepatitis C. The impact of polymorphism of interleukin-28B (IL28B) on sustained virological response (SVR) to PR has been well documented in patients with CHC genotype-1 (GT1), but it is controversial in genotype-2 (GT2) CHC patients. This study investigated the predictability of six single nucleotide polymorphisms (SNP) of IL28B on the treatment responses of PR in patients with CHC GT2. Method 197 CHC GT2 consecutive patients who received PR treatment in our prospective cohort were enrolled. Hepatitis C virus (HCV) genotyping, quantification of HCV-RNA and genotyping of the ten SNPs of IL28B were performed. Six SNPs of IL28B were chosen for analysis. The propensity score matching (PSM) analysis was applied using patients with CHC GT1 in another prospective cohort as a positive comparison to avoid covariate bias. Results The distribution of the six SNPs was similar in GT1 and GT2 patients. Five of these SNPs had strong association with treatment responses in GT1 but not in GT2 patients. After PSM analysis, these five SNPs still showed strong association with rapid virological response (RVR), cEVR and SVR in GT1 and had no influence in GT2 patients. Furthermore, rs12979860 and baseline viral load were the predictors for both RVR and SVR in GT1 patients. However, only baseline viral load could predict RVR and SVR in GT2 patients. In addition, in patients without RVR, rs12979860 was the only predictor for SVR in GT1 but no predictor for SVR was found in GT2. Conclusions The genetic polymorphisms of IL28B had no impact on treatment responses in GT2 patients.
    Preview · Article · Nov 2012 · PLoS ONE
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