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Objective: Treatment of chronic hepatitis C virus (HCV) infection with pegylated interferon (PeglFN) and ribavirin causes haematological side effects such as anemia, neutropenia and trombocytopenia. This study aimed to evaluate and compare the haematological side effects of PeglFN α-2a and PeglFN α-2b with ribavirin in the treatment of chronic HCV infection. Methods: 103 patients treated with PeglFN α-2b plus ribavirin and 70 patients treated with PeglFN α-2a plus ribavirin were included in this retrospective study. Patients' haematological parameters in first and third month's visits were compared with pretreatment test results. Results: ln all patients, 21.2% had anemia (haemoglobin <10 g/dL), 3.8% had neutropenia (<750/mm²) and 6.2% had thrombocytopenia (<75x109/L) at the end of the third month. When compared with initial levels, significant decreases in haemoglobin, neutrophil and thrombocyte counts were observed at first and third months in both groups. There wasn't a significant decrease in thrombocyte counts in the first month between two groups, however, a more significant decrease in thrombocyte counts were observed in patients who received PeglFN α-2a plus ribavirin than the patients receiving PeglFN α-2b plus ribavirin during the third month. Conclusions: PeglFN α-2b seems to have similar haematologic side effects, compared with PeglFN α-2a except the effects on the thrombocyte counts during the third month. [ABSTRACT FROM AUTHOR]

Background: Pegylated interferon (PegIFN) plus ribavirin is the standard therapy for patients with chronic hepatitis C genotype 1. Although several randomized clinical trials have compared PegIFNα-2a with PegIFNα-2b, these 2 regimens have not been directly compared in Asian patients. We, therefore, compared the safety and antiviral efficacy of these agents in Japanese patients. Methods: A total of 201 PegIFN-naïve, chronic hepatitis C patients were randomly assigned to once-weekly PegIFNα-2a (180 μg) or PegIFNα-2b (60-150 μg) plus ribavirin. We compared the sustained virological response (SVR) rates between the 2 regimens and analyzed their effects in relation to baseline characteristics, including single nucleotide polymorphisms (SNPs) near the interleukin-28B ( IL28B) gene (rs8099917). Results: PegIFNα-2a was associated with a higher SVR rate than PegIFNα-2b (65.3 vs. 51.0%, P = 0.039). PegIFNα-2a and SNPs near IL28B independently predicted SVR (odds ratio 2.36; 95% confidence interval [CI] 1.19-15.50, and odds ratio 7.31; 95% CI 3.45-4.68, respectively) in logistic regression analysis. PegIFNα-2a was more effective than PegIFNα-2b (81.8 vs. 62.7%, P = 0.014) in IL28B TT genotype patients, despite similarly low SVR rates in patients with TG or GG genotypes (36.4 vs. 35.9%). Patients weighing <60 kg, women, and patients aged >60 years had significantly higher SVR rates with PegIFNα-2a than with PegIFNα-2b (63.9, 61.3, and 67.3% vs. 43.8, 43.3,and 39.2%, respectively). Conclusions: PegIFNα-2a plus ribavirin resulted in higher SVR rates than PegIFNα-2b plus ribavirin in Japanese patients. PegIFNα-2a-based treatment should therefore be the preferred choice for women, older or low-weight patients, and those with the IL28B TT genotype. [ABSTRACT FROM AUTHOR]

Background: The standard treatments for chronic infection with the hepatitis C virus (HCV) are peginterferon α-2a or α-2b plus ribavirin, but it remains unclear if one has a better efficacy and safety profile. Objective: The aim of this study was to perform a meta-analysis of randomized controlled trials (RCTs) comparing peginterferon α-2a and α-2b (in combination with ribavirin) treatments for chronic HCV. Methods: The Cochrane Central Register of Controlled Trials, MEDLINE, Science Citation Index, and EMBASE were searched (1966–April 2010) to identify RCTs that evaluated the sustained virologic response (SVR) to peginterferon α-2a and peginterferon α-2b in patients with chronic HCV. The inclusion criteria were: RCT studies designed to compare the therapeutic effects of peginterferon α-2a (180 μg/wk) and peginterferon α-2b (1.5 μg/kg/wk) for treatment-naive patients with chronic HCV; patients treated for ≥24 weeks if infected with HCV genotypes 2 or 3 and for ≥48 weeks if infected with genotypes 1 or 4, with 24-week follow-ups; and publications written in any language. Reports of duplicated studies were excluded by examining the author list, parent institution, sample size, and results. The primary outcome was the SVR, and the other measures included the liver-related morbidity, all-cause mortality, and adverse events leading to treatment discontinuation. Results: The literature search yielded 5580 studies, and 7 RCTs comprising 3212 patients matched the inclusion/exclusion criteria. Overall, the SVR rate was significantly higher in patients treated with peginterferon α-2a than in patients treated with peginterferon α-2b (50% vs 46%, respectively; relative risk [RR] = 1.11; 95% CI, 1.02–1.20; P < 0.05) and varying levels of ribavirin treatment. The subgroup analysis found that, in patients with genotypes 1 or 4, the difference between SVR rate in patients treated with peginterferon α-2a and patients treated with peginterferon α-2b was not statistically significant (43% vs 39%; RR = 1.25; 95% CI, 0.99–1.57). A significantly higher SVR rate was achieved in the HCV patients with genotypes 2 or 3 treated with peginterferon α-2a compared with the patients treated with peginterferon α-2b (86% vs 77%; RR = 1.11; 95% CI, 1.02–1.22; P = 0.02). The meta-analysis of adverse events leading to treatment discontinuation revealed no significant differences between the 2 treatments. Conclusions: The evidence reviewed in this meta-analysis suggests that peginterferon α-2a treatment was associated with a higher SVR rate than peginterferon α-2b treatment in patients with chronic HCV also treated with ribavirin. However, the available evidence on adverse events was insufficient to make recommendations. [Copyright &y& Elsevier]

In patients with chronic hepatitis C, rapid virological response (RVR) at week 4 of treatment seems to be strongly associated with a high probability of achieving a sustained virological response (SVR). The aim of this study was to investigate the outcome of different pegylated interferon-α2b (Peg-IFN-α2b) dosages plus ribavirin (RBV) in patients with RVR. Forty-five naïve patients chronically infected with hepatitis C virus (HCV)-1b started Peg-IFN-α2b (1.5 μg/kg/week) in combination with weight-based RBV doses (800–1200 mg/day). Thirty-one patients (68.9%) attained RVR at week 4 of therapy, while four further patients showed negative HCV-RNA values for the first time at week 12 and were considered early virological responders (EVR). The 31 RVR patients were randomized to receive either RBV plus 1.5 μg/kg/week (17 pts) or 1.0 μg/kg/week (14 pts) of Peg-IFN-α2b for the remaining 44 weeks. The two groups were matched for age, sex, baseline alanine aminotransferase levels, viral load and fibrosis score. After 6 months of post-treatment follow-up, the prevalence of SVR was 94.1% (16/17) among RVR patients treated with 1.5 μg/kg/week and 92.8% (13/14) in RVR patients treated with 1.0 μg/kg/week ( P = not significant). A high-baseline viral load ( P = 0.01) and bridging fibrosis/cirrhosis ( P = 0.02) negatively influenced the likelihood of achieving RVR. On the contrary, the ability of RVR patients to achieve SVR did not correlate with these baseline characteristics in either of the treatment group. Finally, the SVR rate among EVR patients who responded after more than 4 weeks of treatment was significantly lower than among RVR patients (1/4 = 25% vs 29/31 = 93.5%; P = 0.0058), because of a high prevalence of post-treatment relapse among patients with EVR. [ABSTRACT FROM AUTHOR]

Current models used to predict response to peginterferon plus ribavirin treatment, based on viral decline during the first 12 weeks of therapy, have focused on creating an early stopping rule to avoid unnecessary prolongation of therapy. We developed a multivariate model that predicted sustained virological response and nonresponse at baseline and during the first 12 weeks of therapy using collected data from 186 unselected patients with chronic hepatitis C treated with peginterferon plus ribavirin. This model employed ordinal regression with similarity least squares technology to assign the probability of a given outcome. Model variables include sex, age, prior treatment status, genotype, baseline serum alanine aminotransferase levels, histologic necroinflammation and fibrosis scores and serum hepatitis C virus RNA concentration at baseline and weeks, 4, 8, and 12. A multivariate model demonstrated high performance values at all time points. At baseline, the model demonstrated a negative predictive value (NPV) and a positive predictive value (PPV) of 91% and 95%, respectively. At week 4, these values improved to 97% and 100%, respectively, with 95% sensitivity, 89% specificity and 93% accuracy. At week 4, the model was equally efficient for naïve or previously treated patients. Internal validation demonstrated 90% PPV, 94% NPV, 95% sensitivity, 88% specificity and 92% accuracy. A week 4 stopping rule for patients with chronic hepatitis C treated with peginterferon with ribavirin might be proposed by using the model developed in our study. [ABSTRACT FROM AUTHOR]

Previous studies in Caucasian patients showed treatment of chronic hepatitis C with pegylated interferon/ribavirin was well tolerated, and produced a higher response rate especially in genotype 1 infections. However, it is unknown whether this conclusion can be extrapolated to patients with Chinese ethnic origin. A total of 153 patients with biopsy-proven chronic hepatitis C were randomly assigned to receive either weekly injection of peginterferonα-2b 1.5 mcg/kg plus oral ribavirin (1000 or 1200 mg/day, depending on body weight) (PEG group,n = 76) or 3 MU of interferonα-2b t.i.w. plus ribavirin (IFN group,n = 77) for 24 weeks. Sustained virological response (SVR) was defined as the sustained disappearance of serum hepatitis C virus (HCV) RNA at 24 weeks after the end of treatment by polymerase chain reaction assay. Baseline demographic, viral and histological characteristics were comparable between the two groups. Using an intent-to-treat analysis, HCV genotype 1 patients showed a significantly higher SVR in patients receiving PEG-IFN rather than IFN (65.8%vs41.0%,P = 0.019), but no difference was found in genotype non-1 patients (PEGvsIFN: 68.4%vs86.8%,P = 0.060). Genotype 1 patients (28.6%) in the PEG-IFN group relapsed, as compared with 52.9% in the IFN group (P = 0.040). Multivariate analyses showed early virological response at week 12 of therapy and genotype non-1 were significant predictors to SVR. As compared with the IFN group, patients receiving PEG-IFN had a significantly higher rate of discontinuation, dose reduction, fever, headache, insomnia, leucopenia and thrombocytopenia. In genotype 1 chronic hepatitis C Chinese patient, PEG-IFNα2b ribavirin had significantly better SVR and lower relapse rate when compared to IFN/ribavirin. Both regimens can be recommended for genotype non-1 chronic hepatitis C Chinese patients. However, a higher rate of adverse events and discontinuance of therapy were noted in patients treated with PEG-IFNα2b ribavirin. [ABSTRACT FROM AUTHOR]

Gallegos-Orozco JF, Loaeza-del Castillo A, Fuentes AP, García-Sandoval M, Soto L, Rodríguez R, Gutiérrez-Ruíz MC, Gutiérrez-Reyes G, Bonder A, Olivera MA, Kershenobich D. Early hepatitis C virus changes and sustained response in patients with chronic hepatitis C treated with peginterferonα-2b and ribavirin.Liver International 2005: 25: 91–95.© Blackwell Munksgaard 2005Interferon-based therapy induces changes in viral dynamics in chronic hepatitis C (CHC) patients.The aim of this study was to assess early hepatitis C virus (HCV)-RNA changes and evaluate its predictive value to achieve sustained viral response (SVR) in patients with CHC treated with peginterferonα-2b weekly plus ribavirin daily for 48 weeks.HCV-RNA was measured at baseline, 48 h, 4, 12, 24 and 48 weeks of treatment and 24 weeks after treatment.Eighteen HCV genotype 1 patients were included (13 male, five female) with a mean age of 44.4±11.9 years. Nine patients achieved SVR (50%). Viral decline occurred as early as 48 h; the magnitude of decline was statistically different between both groups (P<0.01). Responders had a≥1 log10 drop in HCV-RNA at 48 h (positive predictive value (PPV) of 89% to achieve SVR) that persisted at week 4. By week 12, serum HCV-RNA was undetectable (PPV 100%).Our data indicate that peginterferonα-2b plus ribavirin treatment produces significant changes in HCV dynamics that can be detected as early as 48 h after the first dose of peginterferonα-2b and that these changes are useful in predicting response to therapy in CHC patients. [ABSTRACT FROM AUTHOR]