Peginterferon Alfa-2b or Alfa-2a with Ribavirin for Treatment of Hepatitis C Infection

Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27715, USA.
New England Journal of Medicine (Impact Factor: 55.87). 09/2009; 361(6):580-93. DOI: 10.1056/NEJMoa0808010
Source: PubMed


Treatment guidelines recommend the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus (HCV) infection. However, these regimens have not been adequately compared.
At 118 sites, patients who had HCV genotype 1 infection and who had not previously been treated were randomly assigned to undergo 48 weeks of treatment with one of three regimens: peginterferon alfa-2b at a standard dose of 1.5 microg per kilogram of body weight per week or a low dose of 1.0 microg per kilogram per week, plus ribavirin at a dose of 800 to 1400 mg per day, or peginterferon alfa-2a at a dose of 180 microg per week plus ribavirin at a dose of 1000 to 1200 mg per day. We compared the rate of sustained virologic response and the safety and adverse-event profiles between the peginterferon alfa-2b regimens and between the standard-dose peginterferon alfa-2b regimen and the peginterferon alfa-2a regimen.
Among 3070 patients, rates of sustained virologic response were similar among the regimens: 39.8% with standard-dose peginterferon alfa-2b, 38.0% with low-dose peginterferon alfa-2b, and 40.9% with peginterferon alfa-2a (P=0.20 for standard-dose vs. low-dose peginterferon alfa-2b; P=0.57 for standard-dose peginterferon alfa-2b vs. peginterferon alfa-2a). Estimated differences in response rates were 1.8% (95% confidence interval [CI], -2.3 to 6.0) between standard-dose and low-dose peginterferon alfa-2b and -1.1% (95% CI, -5.3 to 3.0) between standard-dose peginterferon alfa-2b and peginterferon alfa-2a. Relapse rates were 23.5% (95% CI, 19.9 to 27.2) for standard-dose peginterferon alfa-2b, 20.0% (95% CI, 16.4 to 23.6) for low-dose peginterferon alfa-2b, and 31.5% (95% CI, 27.9 to 35.2) for peginterferon alfa-2a. The safety profile was similar among the three groups; serious adverse events were observed in 8.6 to 11.7% of patients. Among the patients with undetectable HCV RNA levels at treatment weeks 4 and 12, a sustained virologic response was achieved in 86.2% and 78.7%, respectively.
In patients infected with HCV genotype 1, the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferon-ribavirin regimens or between the two doses of peginterferon alfa-2b. ( number, NCT00081770.)

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    • "During the last decade, the standard therapy for chronic hepatitis C infection is treatment with pegylated interferon-␣ that is administrated as a monotherapy or in combination with ribavirin (Jun et al., 2012; McHutchison et al., 2009). The response rate to this therapy differs among patients as the HCV genotype is a strong prognostic factor for sustained virological response (Blum, 2003; Saracco et al., 2003; Seeff and Hoofnagle, 2003). "
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    ABSTRACT: The genotype of the hepatitis C virus (HCV) is an important indicator for antiviral therapeutic response. We hereby described development of a rapid HCV genotyping approach that enabled the identification of the six most common HCV subtypes of Asia, i.e., 1a, 1b, 2a, 3a, 3b, and 6a, in a single reaction. By using two dual-labeled, self-quenched probes that target the core region of the HCV genome, the exact subtype could be accurately identified by two-melting temperature codes determined from the two respective probes in a real-time PCR assay. Analytical sensitivity studies using armored RNA samples representing each of the six HCV subtypes showed that 5 copies/reaction of HCV RNA could be detected. The assay was evaluated using 244 HCV-positive serum samples and the results were compared with sequencing analysis. Of the 224 samples, subtype 3a (127, 52.3%) was the dominant, followed by 1b (51, 20.9%), 3b (47, 19.3%), 2a (8, 3.3%), 6a (4, 1.6%) and the least was subtype 1a (1, 0.4%). Moreover, 6 (2.5%) mixed infection samples were also detected. These results were fully concordant with sequencing analysis. We concluded that this real-time PCR-based assay could provide a rapid and reliable tool for routine HCV genotyping in most Asian countries. Copyright © 2015. Published by Elsevier B.V.
    Journal of virological methods 06/2015; 74. DOI:10.1016/j.jviromet.2015.05.013 · 1.78 Impact Factor
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    • "Parameter Pre-treatment (n = 12) 4th week of treatment (n = 12) Pre-treatment vs. 4th week p value 12th week of treatment (n = 12) 4th vs. 12th week p value Pre-treatment vs. 12th week p value Age (years) 48.08 ± 3.55 48.08 ± 3.55 48.08 ± 3.55 HCV-RNA (IU/mL) 1443370.83 ± 395745.68 3705.08 ± 1734.24 0.002 601.58 ± 520.90 0.012 0.002 TRAIL (pg/mL) 300.24 ± 13.11 274.23 ± 8.37 0.034 228.39 ± 8.76 0.011 0.002 WBC (mm 3 ) 6833.33 ± 731.37 3708.33 ± 236.60 0.002 3216.67 ± 282.80 0.041 0.002 Hemoglobulin (g/dL) 13.39 ± 0.49 11.59 ± 0.49 0.003 11.03 ± 0.36 0.064 0.002 Platelets (mm 3 ) 185583.33 ± 13161.85 152416.67 ± 12010.39 0.024 134916.67 ± 11595.75 0.032 0.003 MPV (um 3 ) 11.08 ± 0.36 11.23 ± 0.43 0.078 11.27 ± 0.32 0.08 0.078 ALT (U/L) 61.67 ± 11.22 34.67 ± 10.65 0.002 24.17 ± 3.89 0.057 0.004 AST (U/L) 57.33 ± 17.00 30.33 ± 6.42 0.005 27.42 ± 2.89 0.064 0.016 AFP (ng/mL) 4.65 ± 0.69 3.67 ± 0.39 0.017 2.93 ± 0.40 0.023 0.006 sTRAIL levels decreased during treatment of chronic hepatitis C 5652 Int J Clin Exp Med 2014;7(12):5650-5656 ribavirin [10] [11] "
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    ABSTRACT: The molecular mechanisms and pathogenesis of chronic hepatitis C (CHC) infection are unclear. Innate immune cells such as natural killer (NK) cells and dendritic cells are responsible from molecular mechanism of CHC. NK cell cytotoxicity such as TRAIL expression is important pathway for viral clearance. The aim of this study was to evaluate the relationship between HCV RNA and sTRAIL levels during the first 12 weeks of Peg-IFNα and ribavirin treatment. Twelve treatment naive patients with CHC treated with Peg-INFα and ribavirin were included in this study. Circulating sTRAIL and HCV RNA levels were measured at baseline, 4th and 12th week of treatment and their correlation was investigated. sTRAIL and HCV RNA levels decreased gradually with Peg-INFα plus ribavirin treatment. The differences were significant between day 0, 4th week and 12th week of treatment. The expression of sTRAIL was correlated with HCV RNA level at baseline, at 4th and 12th week of treatment (P = 0.021 P = 0.012, P = 0.001 respectively). IFN binds to its receptor on the infected hepatocyte surface during Peg-IFNα and ribavirin treatment. So the polarized phenotype of NK cell is not displayed and NK cell cytotoxicity such as TRAIL expression is blocked. We suggest that the decreased level of circulating sTRAIL may reflect increased binding to its ligand expressed on hepatocyte and decreased TRAIL production under the influence of Peg-IFNα plus ribavirin treatment. Therefore TRAIL may be probably a immunologically predictive factor such as HCV RNA during treatment.
    International Journal of Clinical and Experimental Medicine 12/2014; 7(12). · 1.28 Impact Factor
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    • "Antiviral combination therapy consisting of pegylated interferon-α and ribavirin (PEG-IFN-α/RBV) for treatment of chronic hepatitis C virus (CHC) infection is highly effective but it is also difficult to tolerate in some patients. In fact, it is associated with significant morbidity and with treatment-limiting adverse events [1]. One important treatment-limiting adverse event is anemia. "
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    ABSTRACT: Background A decline in hemoglobin (Hb) concentration during antiviral therapy in chronic hepatitis C (CHC) is a serious side effect. It may compel to dose reduction or even termination of antiviral treatment. The activation of erythropoietin (EPO) synthesis as a physiological response to anemia and its relation to a genetic variation within the EPO gene has not been evaluated yet. Methods Data of 348 CHC patients were reviewed retrospectively. Samples were genotyped for EPO rs1617640 and inosine triphosphatase (ITPA) rs1127354. Serum EPO concentrations were determined before and during therapy. Primary endpoints were set as Hb decline >3 g/dl at weeks 4 and 12. Results EPO rs1617640 G homozygotes showed a significantly lower rise of serum EPO level over time than T allele carriers (p < 0.001). The cumulative frequency of a significant Hb reduction added up to 40%. Multivariate analysis revealed that besides age, ribavirin starting dose and baseline Hb also EPO rs1617640 G homozygosity associates with Hb reduction at week 4 (p = 0.025) and 12 (p = 0.029), while ITPA C homozygotes are at risk for Hb decline particularly early during treatment. Furthermore, EPO rs1617640 G homozygotes were more frequently in need for blood transfusion, epoetin-α supplementation, or ribavirin dose reduction (p < 0.001). Conclusions Our data suggest that EPO rs1617640 genotype, the rise of serum EPO concentration as well as ITPA rs1127354 genotype are promising parameters to evaluate the Hb decline during antiviral therapy. A rational adjustment of therapy with epoetin-α supplementation might prevent serious adverse events or the need to terminate treatment.
    BMC Infectious Diseases 09/2014; 14(1):503. DOI:10.1186/1471-2334-14-503 · 2.61 Impact Factor
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