Eight-week regimen of antiviral combination therapy with peginterferon and ribavirin for patients with chronic hepatitis C with hepatitis C virus genotype 2 and a rapid virological response
ABSTRACT It remains unclear how we can shorten the treatment duration of antiviral combination therapy with peginterferon and ribavirin for patients with chronic hepatitis C virus (HCV) genotype 2 infection who achieved a rapid virological response (RVR).
We compared the efficacy of antiviral combination therapy with peginterferon and ribavirin for 8 vs. 24 weeks for the treatment of patients with HCV genotype 2 infection and with RVR.
Sixty-one patients were enrolled. Serum HCV RNA was not detected at 4 weeks after the start of treatment in 32 patients with an RVR. These 32 patients were randomly assigned to 8-week (n=15) or 24-week (n=17) treatment regimens. Patients in the 8-week group who relapsed underwent a 24-week retreatment.
No significant difference in patient characteristics was observed between the 8- and the 24-week treatment groups. A sustained virological response (SVR) was seen in five of 15 patients (33.3%) in the 8-week treatment group and 14 of 17 (82.4%) in the 24-week treatment group; the rate was significantly higher in the 24-week treatment group (P=0.0140). Nine of 10 relapsed patients in the 8-week treatment group underwent a 24-week retreatment, and seven achieved an SVR.
An 8-week regimen of combination antiviral therapy with peginterferon and ribavirin yielded an increase in the relapse rate, indicating the limitation of a reduction of treatment below 12 weeks in patients with genotype 2, after RVR.
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ABSTRACT: BACKGROUND: Pegylated interferon (PEG-IFN) plus ribavirin (RBV) therapy is the current standard of care for patients with chronic hepatitis C. Determining precisely the risk of serious adverse events (SAEs) and mortality from a single study is rather difficult because of the infrequency of such events. The aim of this systematic review was to assess the rates of SAEs and the mortality of PEG-IFN/RBV therapy in a pooled large sample, and to assess the relationship between SAEs and mortality rates and therapeutic characteristics. METHODS: A literature search was conducted using MEDLINE, EMBASE, and the Cochrane Library to identify randomized controlled trials evaluating the efficacy and safety of PEG-IFN/RBV therapy. We calculated the crude mortality and SAE rates with 95 % confidence intervals (CIs). RESULTS: Eighty studies with 153 treatment arms that included 27569 patients were enrolled (14401 patients treated with Peg-IFN alpha-2a/RBV and 13168 with Peg-IFN alpha-2b/RBV). All-cause and treatment-related deaths were observed in 50 (0.18 %; 95 % confidence interval [CI] 0.13-0.24 %) and sixteen (0.058 %; 95 % CI 0.033-0.094 %) patients, respectively. The crude SAE rate was 7.08 % (95 % CI 6.75-7.41 %). Subgroup analysis revealed higher SAE rates in patients receiving PEG-IFN alpha-2a than in those with PEG-IFN alpha-2b (7.45 vs. 6.74 %), and higher SAE rates with higher doses than with the lower doses in PEG-IFN-2a and 2b (11.94 vs. 6.99 %, 7.10 vs. 5.05 %, respectively), and with extended duration (>48 weeks) than with standard duration (48 weeks) (15.5 vs. 6.67 %) in PEG-IFN alpha-2a. CONCLUSION: The mortality rate during PEG-IFN/RBV therapy was acceptably low, but the rate of SAEs was not negligible in a treatment for a benign disease, and the rate was affected by treatment regimens.Journal of Gastroenterology 07/2012; DOI:10.1007/s00535-012-0631-y · 4.02 Impact Factor
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ABSTRACT: The impacts of IL28B genotype to treatment response of hepatitis C virus (HCV) genotype 2 are still not clear. A total of 381 consecutive Japanese patients infected with HCV genotype 2, who could complete combination therapy with interferon (IFN) plus ribavirin for 24 weeks, were evaluated to investigate pretreatment predictors. Patients, who could not achieve sustained virological response at the first course of 24-week IFN plus ribavirin, were recruited into the study protocol of total 48-week IFN plus ribavirin. In 24-week regimen, rates of sustained virological response and rapid virological response were 82% and 50%, respectively. There were no significant differences in rates of sustained virological response and rapid virological response, according to IL28B genotype. Multivariate analysis identified younger age, higher level of albumin, absence of past history of IFN, and lower level of viremia as significant determinants of sustained virological response. As significant or marginal significant determinants of non-sustained virological response regardless of rapid virological response, multivariate analysis identified IL28B rs8099917 genotype TG + GG and lower level of albumin. In 48-week regimen to 10 patients of non-sustained virological response at the first course of 24-week regimen, sustained virological response rates were 70%. All of six patients, with IL28B TT and relapse at the first course of 24-week regimen, could achieve sustained virological response, but two patients with IL28B TG could not achieve sustained virological response. In conclusion, the present results suggest that IL28B genotype might partly affect viral response of HCV genotype 2 to combination therapy.Journal of Medical Virology 10/2012; 84(10):1593-9. DOI:10.1002/jmv.23368 · 2.22 Impact Factor
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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.Journal of Medical Virology 09/2013; 85(9). DOI:10.1002/jmv.23626 · 2.22 Impact Factor