Early virologic response after peginterferon alpha-2a plus ribavirin or peginterferon alpha-2b plus ribavirin treatment in patients with chronic hepatitis C

Patients infected with hepatitis C virus (HCV) genotype 1 and with serum HCV RNA concentrations over 800 000 IU/mL have relatively low rates of virologic response to pegylated interferons. The 2 forms of pegylated interferon have different pharmacokinetic profiles, and pilot studies comparing them have yielded varying results. We compared the virologic response to 12 weeks of treatment with peginterferon alpha-2a plus ribavirin vs peginterferon alpha-2b plus ribavirin in 380 patients who were infected with HCV genotype 1 and had high viral loads. We observed no between-group differences in viral load reduction over time and no differences in the percentage of patients treated with peginterferon alpha-2a or peginterferon alpha-2b plus ribavirin who achieved early virologic response (EVR), defined as >/=2-log reduction in HCV RNA concentration or undetectable HCV RNA at 12 weeks (66%vs 63%). Serum levels of interferon were more frequently below the level of quantitation in patients treated with peginterferon alpha-2b plus ribavirin (58-68%) than in those treated with peginterferon alpha-2a plus ribavirin (1-2%). Patients treated with peginterferon alpha-2b plus ribavirin had higher rates of discontinuation for safety reasons (6%vs 1%). In conclusion, a substantial percentage of patients infected with HCV genotype 1 and high viral load can achieve EVR when treated with peginterferon and ribavirin. The 2 pegylated interferons showed comparable anti-HCV activity during the first 12 weeks of treatment when combined with the same doses of ribavirin (1000-1200 mg/day), but discontinuations for safety reasons were higher in the patients treated with peginterferon alpha-2b plus ribavirin.     

Comparison of a 6-month course peginterferon alpha-2b plus ribavirin and interferon alpha-2b plus ribavirin in treating Chinese patients with chronic hepatitis C in Taiwan

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 peginterferon alpha-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 interferon alpha-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%vs 41.0%, P = 0.019), but no difference was found in genotype non-1 patients (PEG vs IFN: 68.4%vs 86.8%, 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-IFNalpha2b 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-IFNalpha2b ribavirin.     

Peginterferon alpha-2b plus ribavirin for chronic hepatitis C virus mixed genotype infection

Background and aim. The treatment efficacy of peginterferon plus ribavirin for patients with HCV genotype 1 is inferior to that in patients with HCV genotype 2, but the efficacy among patients with mixed HCV genotype 1 + 2 is less clear. We compared the treatment outcome of peginterferon alpha-2b plus ribavirin among naïve chronic hepatitis C patients in Taiwan with HCV genotype 1 and 2, and mixed genotype 1 + 2.Material and methods. In this retrospective cohort study, 150 patients were treated with peginterferon alpha-2b once weekly, plus ribavirin, for 24 weeks. The endpoint was sustained virological response after receiving at least one dose of the study medication.Results. There were no differences in clinical characteristics among the 3 groups. There were significant differences in rapid virological response rate between patients with genotype 1 and genotype 2 (64.7 vs. 85.5%, respectively; p < 0.05) and a sustained virological response rate (55.9 vs. 83.6%, respectively; p = 0.001). The rapid virological response rate differed between the genotype 1 and mixed genotype 1 + 2 groups (64.7 vs. 85.2%, respectively; p < 0.05), but the sustained virological response rate was similar (55.9 vs. 74.1%; p = 0.101). Conclusions. Using peginterferon alpha-2b plus ribavirin for 24 weeks to treat patients with HCV genotype 1 + 2 achieved a 74.1% sustained virological response rate; the treatment efficacy was not inferior to patients with HCV genotype 1, but the percentage of liver cirrhosis in mixed genotype 1 + 2 group was higher to 22%, it is worth to be appropriately valued and studied.     

Peginterferon alpha-2b plus ribavirin compared with interferon alpha-2b plus ribavirin for initial treatment of chronic hepatitis C in Saudi patients commonly infected with genotype 4.

AIM: Comparing the efficacy of peginterferon alpha-2b plus ribavirin with interferon alpha -2b plus ribavirin in Saudi patients with chronic hepatitis C virus (HCV) commonly infected with genotype 4. METHODS: A total of 96 patients with chronic HCV infection were randomly assigned to two treatment groups. Forty-eight patients received once weekly 100 microg of peginterferon alpha-2b plus ribavirin given orally 800 mg/day (peginterferon group). Another 48 patients received thrice weekly 3 million units of interferon alpha-2b plus ribavirin 800 mg/day (interferon group). At the end of treatment (48 weeks) and sustained (72 weeks) biochemical and virologic responses were determined. RESULTS: In the peginterferon group, 70.8% (34/48) patients attained both biochemical and virologic responses at the end of the treatment as against 52.1% (25/48) patients in the interferon group. (P=0.09 for both). Similarly, sustained biochemical and virologic responses in the peginterferon group were attained in 52.1% (25/48) and 43.8% (21/48) patients as against 43.8% (21/48) and 29.2% (14/48) patients in the interferon group, respectively (P=0.54 and 0.20, respectively). The sustained virologic response rates in patients with genotype 4 were 42.9% (12/28) in the peginterferon group and 32.3% (10/31) in the interferon group (P=0.43). Patients in peginterferon group had higher, although statistically not significant adverse reactions. CONCLUSIONS: Saudi patients with chronic HCV attained a higher, although statistically not significant sustained virologic response with pegylated interferon plus ribavirin compared with interferon plus ribavirin.     

Cost-effectiveness of combination peginterferon alpha-2a and ribavirin compared with interferon alpha-2b and ribavirin in patients with chronic hepatitis C

BACKGROUND: Sustained virological response (SVR) is the primary objective in the treatment of chronic hepatitis C (CHC). Results from a recent clinical trial of patients with previously untreated CHC demonstrate that the combination of peginterferon alpha-2a and ribavirin produces a greater SVR than interferon alpha-2b and ribavirin combination therapy. However, the cost-effectiveness of peginterferon alpha-2a plus ribavirin in the U.S. setting has not been investigated. METHODS: A Markov model was developed to investigate cost-effectiveness in patients with CHC using genotype to guide treatment duration. SVR and disease progression parameters were derived from the clinical trials and epidemiologic studies. The impact of treatment on life expectancy and costs were projected for a lifetime. Patients who had an SVR were assumed to remain virus-free for the rest of their lives. In genotype 1 patients, the SVRs were 46% for peginterferon alpha-2a plus ribavirin and 36% for interferon alpha-2b plus ribavirin. In genotype 2/3 patients, the SVRs were 76% for peginterferon alpha-2a plus ribavirin and 61% for interferon alpha-2b plus ribavirin. Quality of life and costs were based on estimates from the literature. All costs were based on published U.S. medical care costs and were adjusted to 2003 U.S. dollars. Costs and benefits beyond the first year were discounted at 3%. RESULTS: In genotype 1, peginterferon alpha-2a plus ribavirin increases quality-adjusted life expectancy (QALY) by 0.70 yr compared to interferon alpha-2b plus ribavirin, producing a cost-effectiveness ratio of $2,600 per QALY gained. In genotype 2/3 patients, peginterferon alpha-2a plus ribavirin increases QALY by 1.05 yr in comparison to interferon alpha-2b plus ribavirin. Peginterferon alpha-2a combination therapy in patients with HCV genotype 2 or 3 is dominant (more effective and cost saving) compared to interferon alpha-2b plus ribavirin. Results weighted by genotype prevalence (75% genotype 1; 25% genotype 2 or 3) also show that peginterferon alpha-2a plus ribavirin is dominant. Peginterferon alpha-2a and ribavirin remained cost-effective (below $16,500 per QALY gained) under sensitivity analyses on key clinical and cost parameters. CONCLUSION: Peginterferon alpha-2a in combination with ribavirin with duration of therapy based on genotype, is cost-effective compared with conventional interferon alpha-2b in combination with ribavirin when given to treatment-na?ve adults with CHC.     

Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon alpha-2a (40 kd)/ribavirin therapy

Approximately one third of hepatitis C virus (HCV) genotype 1 patients achieved a sustained virological response (SVR) after 24 weeks of treatment with peginterferon alpha-2a (40 kd) plus ribavirin in a randomized, multinational trial. We aimed to identify factors associated with a rapid virological response (RVR) at week 4 (HCV RNA <50 IU/mL) and a SVR (HCV RNA <50 IU/mL at the end of follow-up) in these patients. Stepwise multiple logistic regression analysis was used to explore the prognostic factors for a RVR and SVR in genotype 1 patients treated for 24 weeks. Fifty-one of 216 (24%) genotype 1 patients in the 24-week treatment groups had a RVR. SVR rates were considerably higher in patients with than without [corrected] a RVR (89% vs. 19%, respectively). Patients with a baseline HCV RNA of less than 200,000 IU/mL (OR 9.7, 95% CI 4.2-22.5; P < .0001) or 200,000-600,000 IU/mL (OR 5.6, 95% CI 1.5-9.1; P = .0057) were more likely to achieve a RVR than those with HCV RNA greater than 600,000 IU/mL. HCV subtype (1b vs. 1a) was also independently associated with RVR (OR 1.8, 95% CI 0.9-3.7; P = .0954). RVR (OR 23.7 vs. no RVR, 95% CI 9.1-61.7) and baseline HCV RNA less than 200,000 IU/mL (OR 2.7 vs. > 600,000 IU/mL, 95% CI 1.1-6.3; P < .026) were significant and independent predictors of SVR in patients treated for 24 weeks. In conclusion, patients infected with HCV genotype 1 and treated with peginterferon alpha-2a/ribavirin sustained a RVR 24% of the time. This portends an 89% probability of a SVR after 24 weeks of treatment.     

聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎的疗效及其影响因素

目的 观察聚乙二醇干扰素(PegIFN)α-2a联合利巴韦林(RBV)治疗慢性丙型肝炎患者的疗效及其影响因素,探讨治疗时间及药物累积用量与疗效之间的关系.方法对117例慢性丙型肝炎患者给予PegIFN α-2a联合RBV抗病毒治疗,PegIFN α-2a每周1次,皮下注射135 μg或180 μg,RBV按体质量每日分次口服800～1200mg,共治疗48周.分别在用药前,用药后4、12、24、36、48周以及停药后24周检测HCV RNA载量,检测部分患者HCV基因型,观察病毒学应答情况并分析影响疗效的因素.计数资料的比较用x2检验,P＜0.05为差异有统计学意义.结果 行基因型检测的29例患者中,1b型HCV感染21例,2a型HCV感染7例,1b和2a型混合HCV感染1例.117例患者中,88例获得了快速病毒学应答,96例(82.1%)获得了持续病毒学应答(SVR).年龄≤40岁、体质量＜75 kg、感染时间＜10年的患者可获得更好的疗效,SVR率明显高于年龄＞40岁、体质量≥75 kg、感染时间≥10年者(91.4%比72.9%,x2=6.796,P＜0.05;85%比50%,x2=5.433,P＜0.05;96.7%比77%,x2=5.852,P＜0.05).坚持全疗程的80%以上及PegIFN α-2a或RBV预计累积用量的80%以上可获得更好的疗效(x2值分别为16.971、16.971和43.212,P值均＜0.01).即使给予患者足够剂量的PegIFN α-2a(≥推荐剂量的80%),RBV减量(＜推荐剂量的80%)亦会使其SVR率下降[75.0%(27/36)比96.8%(60/62),x2=8.762,P＜0.01];获得快速病毒学应答的患者SVR率也明显下降[100.0%(51/51)比81.8%(18/22),x 2=6.614,P＜0.05].结论 PegIFN α-2a联合RBV治疗慢性丙型肝炎疗效显著,坚持80%PegIFN α-2a推荐剂量,80%以上RBV推荐剂量,以及80%推荐疗程可获得更好的疗效.

Abstract：

Objective To evaluate the efficacy and to investigate the association between the length of the treatment period and the cumulative dose of pegylated interferon alpha-2a (PegIFN alpha-2a) plus ribavirin (RBV) and the effectiveness of antiviral therapy. Methods We analyzed data from 117 patients treated for 48 weeks with PEG-IFN alpha-2a (135 μ g or 180 μ g/week) plus weight-based RBV (800 mg/dfor patients ≤65 kg, 1000 mg/d for patients 65-75 kg and 1200 mg/d for patients ≥75 kg) under care at West China Hospital. HCV RNA was assessed at baseline, Week 4, 12 and 24, the end of treatment (EOT) and after 24 weeks follow-up (sustained virological response; SVR) with a test range of 1.0 x 103 to 5.0 x 107 IU/ml.Patients were stratified by age, gender, weight, route of transmission, duration of infection, baseline HCV RNA level and PegIFN alpha-2a or RBV dosage. Results HCV genotype was assessed in 29 patients (genotype 1b, 21; genotype 2a, 7; genotype 1b/2a, 1). Rapid virological response (RVR; HCV RNA negative at week 4), complete early virological response (cEVR; HCV RNA negative at week 12), EOT response, and SVR were achieved in 88 (75.2%), 110 (94%), 114 (97.4%) and 96 (82.1%) patients, respectively. Younger age, lower weight and shorter speculated infection years were associated with higher SVR rates (91.4% vs 72.9%, x2 = 6.796, P ＜ 0.05; 85% vs 50%, x2 = 5.433, P ＜ 0.05; 96.7% vs 77%, x2 = 5.852, P ＜ 0.05). SVR significantly increased with treatment length (38.5%, 66.7%, and 88.8% for ≤ 29 weeks, 29-38 weeks, and ≥38 weeks, respectively). SVR significantly increased with total cumulative treatment doses (38.5%, 66.7% and 88.8% for ≤ 60%, 60%-80% and ≥ 80% of PegIFN dose respectively; 33.3%, 85.3% and 96.8% for ≤ 60%,60%-80% and ≥ 80% in RBV dose respectively) in all patients. Less than 80% of standard dose of RBV was not sufficient even if given enough PegIFN (≥ 80% cumulative treatment dose) in patients who achieved RVR. Conclusion Chinese patients treated with peginterferon alpha-2a plus ribavirin have high rates of SVR.It is important to complete the target length of treatment and to continue the target dosage to achieve SVR.     

Cost effectiveness of peginterferon alpha-2b plus ribavirin versus interferon alpha-2b plus ribavirin for initial treatment of chronic hepatitis C

BACKGROUND: Peginterferon alpha-2b plus ribavirin therapy in previously untreated patients with chronic hepatitis C yields the highest sustained virological response rates of any treatment strategy but is expensive. AIMS: To estimate the cost effectiveness of treatment with peginterferon alpha-2b plus ribavirin compared with interferon alpha-2b plus ribavirin for initial treatment of patients with chronic hepatitis C. METHODS: Individual patient level data from a randomised clinical trial with peginterferon plus ribavirin were applied to a previously published and validated Markov model to project lifelong clinical outcomes. Quality of life and economic estimates were based on German patient data. We used a societal perspective and applied a 3% annual discount rate. RESULTS: Compared with no antiviral therapy, peginterferon plus fixed or weight based dosing of ribavirin increased life expectancy by 4.2 and 4.7 years, respectively. Compared with standard interferon alpha-2b plus ribavirin, peginterferon plus fixed or weight based dosing of ribavirin increased life expectancy by 0.5 and by 1.0 years with incremental cost effectiveness ratios of 11,800 euros and 6600 euros per quality adjusted life year (QALY), respectively. Subgroup analyses by genotype, viral load, sex, and histology showed that peginterferon plus weight based ribavirin remained cost effective compared with other well accepted medical treatments. CONCLUSIONS: Peginterferon alpha-2b plus ribavirin should reduce the incidence of liver complications, prolong life, improve quality of life, and be cost effective for the initial treatment of chronic hepatitis C.     

Treatment effects and predictors of a 24-week course of interferon alpha-2b plus ribavirin combination therapy for patients with chronic hepatitis C

BACKGROUND AND AIMS: In chronic hepatitis C patients with genotype 1b and a high viral load, the sustained virological response (SVR) rate remained as low as 2-3% with conventional interferon (IFN) monotherapy, but improved to more than 20% with IFN alpha-2b plus ribavirin combination therapy. This study examined the therapeutic effects and predictors of this combination therapy. METHODS: Subjects were 105 patients with chronic hepatitis C (73 males, 32 females) with a median age of 53 years (range 19-70 years). Seventy-two patients had genotype lb and 33 patients had genotype 2 (2a or 2b). Six million units (MU) or 10 MU of IFN alpha-2b was administered by intramuscular injection six times a week for the first 2 weeks, and the same amount of IFN was administered three times a week for the following 22 weeks. During the IFN administration period, 600-800 mg of oral ribavirin was administered daily. Patients who were hepatitis C virus (HCV)-RNA negative 24 weeks after the completion of administration were defined as SVR. RESULTS: The overall SVR rate was 39%; 22.2% for the genotype 1b group and 75.8% for the genotype 2 group, and the difference between the groups was significant (P < 0.0001). Multivariate logistic regression analysis indicated that the factors that contributed to SVR include genotype 2, age (younger than 53 years), and an increase in Th2 measured by flow cytometry before and 4 weeks after start of treatment. CONCLUSIONS: The overall SVR rate of IFN alpha-2b plus ribavirin combination therapy for 24 weeks was 39%, and contributing factors for SVR rate include genotype 2, age younger than 53 years and elevated Th2.     

Early hepatitis C virus changes and sustained response in patients with chronic hepatitis C treated with peginterferon alpha-2b and ribavirin.

BACKGROUND: Interferon-based therapy induces changes in viral dynamics in chronic hepatitis C (CHC) patients. AIMS: 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 peginterferon alpha-2b weekly plus ribavirin daily for 48 weeks. METHODS: HCV-RNA was measured at baseline, 48 h, 4, 12, 24 and 48 weeks of treatment and 24 weeks after treatment. RESULTS: 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 > or =1 log(10) 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%). CONCLUSIONS: Our data indicate that peginterferon alpha-2b plus ribavirin treatment produces significant changes in HCV dynamics that can be detected as early as 48 h after the first dose of peginterferon alpha-2b and that these changes are useful in predicting response to therapy in CHC patients.     

Long-term effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis

We assessed the efficacy of interferon (IFN) alpha-2b plus ribavirin therapy in patients with hepatitis C virus (HCV)-related cirrhosis, and elucidated the risk factors for the development of hepatocellular carcinoma (HCC) to determine whether these therapies might reduce the incidence of HCC. One hundred and thirty-two HCV-cirrhotic patients receiving IFN alpha-2b (3 or 5 MU thrice weekly) and oral ribavirin (1,000-1,200 mg/day) for 24 or 48 weeks were analysed. Cumulative incidence of HCC was estimated by the Kaplan-Meier method. The prognostic relevance of clinical variables and HCC occurrence was evaluated by univariate analysis with the log-rank test and by multivariate Cox's regression analysis. A total of 116 patients completed the treatment and 73 (55%) achieved a sustained virological response (SVR). Stepwise logistic regression analysis showed that nongenotype 1b (P < 0.001) and low viral load (P = 0.018) were independent variables of SVR. During a median follow-up period of 37 (12-63) months, HCC developed in 11 patients with non-SVR and five with SVR (P = 0.0178), whereas there was no difference between those with transient biochemical response and nonresponse (P = 0.5970). The Kaplan-Meier method also showed that old age (>or=60 years) (P = 0.0034) and genotype 1b (P = 0.0104) were associated with HCC occurrence. Using Cox's regression analysis, non-SVR (odds ratio = 3.521, P = 0.036), male (odds ratio = 6.269, P = 0.011) and old age (odds ratio = 3.076, P = 0.049) were independent significant risk factors contributing to HCC development. Our results suggest that achieving SVR by IFN alpha-2b plus ribavirin therapy may decrease the incidence of HCC in patients with HCV-related cirrhosis.     

Pegylated interferon alpha-2b plus ribavirin in patients with genotype 4 chronic hepatitis C: The role of rapid and early virologic response

In patients chronically infected with hepatitis C virus (HCV) genotype 4, the optimum duration of therapy and the predictors of sustained virologic response (SVR) have not been adequately determined. In this study, 358 patients with chronic hepatitis C genotype 4 were randomly assigned to pegylated interferon (PEG-IFN) alpha-2b (1.5 mug/kg/week) plus oral ribavirin (10.6 mg/kg/day) for a fixed duration of 48 weeks (control group, n = 50) or for a variable duration (n = 318). In the variable-duration group, patients with undetectable HCV RNA at week 4 were treated for 24 weeks (group A, n = 69), patients with undetectable HCV RNA at week 12 were treated for 36 weeks (group B, n = 79), and the rest of the patients were treated for 48 weeks (group C, n = 160). The primary endpoint was SVR (undetectable HCV RNA 24 weeks after treatment cessation). Groups A-C and the control group had SVR rates of 86%, 76%, 56%, and 58%, respectively. After the study was controlled for predictors, a low baseline histologic grade and stage were associated with SVR (P < 0.029) in all groups. In addition, among patients in group C, older age (P = 0.04), a higher baseline body mass index (P = 0.013), and low baseline HCV RNA (P < 0.001) were also associated with SVR attainment. The incidence of adverse events and the rate of discontinuation were higher in patients in the variable-duration and fixed-duration groups treated for 48 weeks. Conclusion: In patients with chronic hepatitis C genotype 4 and undetectable HCV RNA at weeks 4 and 12, treatment with PEG-IFN alpha-2b and ribavirin for 24 weeks and 36 weeks, respectively, is sufficient.     

Peginterferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C genotype 4

BACKGROUND: The hepatitis C virus (HCV) genotype is an important predictive parameter for the success of pegylated interferon plus ribavirin therapy. To date, most published therapeutic trials have enrolled patients infected mainly with HCV genotypes 1, 2, and 3. Data regarding the responsiveness of genotype 4, the predominant type of HCV in the Middle East, are very limited. OBJECTIVE: To assess the efficacy of peginterferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis caused by HCV genotype 4. METHODS: Sixty-six treatment-naive patients infected with HCV genotype 4 were enrolled in this open label, prospective study. Cohort characteristics included the following: 48 M/18 F, mean age 45 +/- 9 years, and mean weight 74 +/- 8 kg. All patients had raised alanine aminotransferase (ALT) and were compensated. The mean pretreatment HCV-RNA level was 4.2 x 10(6) copies/ml (8.4 x 10(5) iu/ml) and median was 2.15 x 10(6) copies/ml. Twenty patients (29%) exhibited cirrhosis or severe fibrosis on pretreatment liver biopsy specimens. Participants were to receive peginterferon alfa-2b, 1.5 mcg/kg/wk plus ribavirin 1,000-1,200 mg/day for 48 wk. Patients were followed up for 24 wk after completing therapy. End of treatment viral response and sustained viral response (SVR) were defined as the absence of HCV-RNA from serum (<100 copies/ml) at 48 wk of treatment and at the end of follow-up, respectively. Data were analyzed on an intention-to-treat basis. RESULTS: End of treatment and sustained virologic response were 77% and 68%, respectively. Among patients with pretreatment HCV-RNA > or =2 x 10(6) SVR was 55% compared with SVR of 86% among patients with HCV-RNA < 2 x 10(6) (p= 0.05). Patients with cirrhosis or severe fibrosis had significantly lower SVR rate compared to those with mild or no fibrosis (29 vs 84%; p < 0.0002). Three patients (4%) discontinued therapy because of severe flu-like symptoms. Four patients developed hypothyroidism. Dose reduction of ribavirin and peginterferon alfa-2b was necessary in 15% and 6% of the patients, respectively. CONCLUSION: Peginterferon alfa-2b in combination with ribavirin is effective in the treatment of HCV genotype 4. The treatment was well tolerated by most of the patients.     

Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3

BACKGROUND/AIMS: Treatment duration in patients with chronic hepatitis C in the era of standard interferon-alpha plus ribavirin was tailored according to hepatitis C virus (HCV) genotype: patients infected with HCV-1 were treated for 48 weeks, patients infected with HCV-2/3 for 24 weeks. The aim of the present study was to investigate this schedule for HCV-2/3 infected patients in the era of pegylated interferon-alpha plus ribavirin. METHODS: Patients chronically infected with HCV-2 (n=42) or HCV-3 (n=182) were treated with peginterferon alfa-2b 1.5 microg/kg subcutaneously once weekly plus ribavirin 800-1400 mg/day based on body weight for 24 weeks. RESULTS: The end of treatment (EOT) and sustained virologic response (SVR) was higher in patients infected with HCV-2 (100 and 93%, respectively) than in patients infected with HCV-3 (93 and 79%, respectively). Baseline viremia (P=0.020), treatment duration >16 weeks (P<0.001) and steatosis (<5%, P=0.015) were significant independent predictors of SVR. Adverse events resulted in discontinuation in 5% and dose reduction in 22% of patients. CONCLUSIONS: Treatment for 24 weeks with peginterferon alfa-2b and ribavirin is sufficient in HCV 2 or 3 infected patients. The lower SVR in patients infected with HCV-3 compared with HCV-2 infected patients may be related to higher levels of steatosis in this population.     

Chronic hepatitis C genotype 1 patients with insulin resistance treated with pioglitazone and peginterferon alpha-2a plus ribavirin

Patients with chronic hepatitis C and insulin resistance are less likely to respond to anti-hepatitis C virus (HCV) therapy and are at risk for more rapid fibrosis progression. Coadministration of pioglitazone with peginterferon/ribavirin improves insulin sensitivity and increases virologic response rates in insulin-resistant HCV genotype 4 patients, but it is unclear whether this finding applies to genotype 1 patients. For this reason we randomized treatment-naive HCV genotype 1 patients with insulin resistance to receive either standard care (peginterferon alpha-2a plus ribavirin for 48 weeks, n = 73) or pioglitazone 30-45 mg/day plus standard care (n = 77) in an open-label multicenter trial. Patients randomized to pioglitazone received the drug during a 16-week run-in phase, the 48-week standard-care phase, and the 24-week untreated follow-up phase. Pioglitazone treatment improved hemoglobin A1c (HbA1c), plasma glucose, insulin levels, and homeostasis model assessment of insulin resistance score and increased serum adiponectin levels during the 16-week run-in phase and maintained these improvements during the standard-care phase. However, we observed no statistically significant difference between the two groups in the primary efficacy endpoint, the decrease from baseline to Week 12 of peginterferon alpha-2a/ribavirin treatment in mean log(10) HCV RNA titer (-3.5 ± 1.71 and -3.7 ± 1.62 IU/mL in the pioglitazone and standard-care groups, respectively, Δ = 0.21 IU/mL, P = 0.4394). CONCLUSION: Treatment with pioglitazone before and during treatment with peginterferon alpha-2a plus ribavirin improved several indices of glycemic control in patients with chronic hepatitis C and insulin resistance, but did not improve virologic response rates compared with peginterferon alpha-2a plus ribavirin alone.     

A randomized trial of pegylated interferon alpha-2b plus ribavirin in the retreatment of chronic hepatitis C

OBJECTIVES: The efficacy of combination therapy with pegylated interferon (PEG IFN) alpha plus ribavirin (RBV) in the retreatment of chronic hepatitis C (CHC) in patients who previously failed combination standard IFN plus RBV or IFN monotherapy has not been well established. METHODS: Three hundred and twenty-one CHC patients including virologic nonresponders to combination IFN plus RBV (n = 219) or IFN monotherapy (n = 47), and relapsers to combination therapy (n = 55) were randomized to receive PEG IFN alpha-2b 1.5 microg/kg per wk plus RBV 800 mg per day (Regimen A, n = 160) or PEG IFN alpha-2b 1.0 microg/kg per wk plus RBV 1,000-1,200 mg per day (Regimen B, n = 161) for 48 wks. RESULTS: Sustained virologic response (SVR) occurred in 16% of the overall study population (Regimen A vs B, 18%vs 13%, p= 0.21), in 8% of the combination therapy nonresponders (10%vs 6%, p= 0.35), in 21% of the IFN monotherapy nonresponders (16%vs 27%, p= 0.35), and in 42% of the combination therapy relapsers (50%vs 32%, p= 0.18). In nonresponders to prior combination therapy, HCV ribonucleic acid levels <100,000 copies/mL at the end of the prior treatment course were associated with an increased SVR compared with levels >or=100,000 copies/mL (21%vs 5%, p= 0.002). In the overall study population, genotype 1 patients had lower SVR rates than others (14%vs 33%, p= 0.01), and African Americans had lower SVR than Caucasians (4%vs 18%, p= 0.01). CONCLUSION: Combination therapy with PEG IFN alpha-2b plus RBV is more effective in patients who relapsed after combination standard IFN plus RBV than in nonresponders to either combination therapy or IFN monotherapy. There was no significant effect of dosing regimen.     

Peginterferon alpha-2b plus ribavirin for treatment of chronic hepatitis C with severe fibrosis: a multicentre randomized controlled trial comparing two doses of peginterferon alpha-2b

We compared sustained virological response (SVR) in chronic hepatitis C patients with severe fibrosis treated with pegylated interferon (Peg-IFN) alpha-2b 1.5 microg/kg/week or 0.75 microg/kg/week in combination with ribavirin 800 mg/day for 48 weeks. This was a multicentre randomized controlled study. SVR was observed in 44.5% (45/101) of patients treated with the standard dose of Peg-IFN and 37.2% (38/102) of patients treated with the low dose (NS). In patients with genotypes 1, 4 and 5, SVR was observed in 25.0% of patients who received the standard dose and 16.9% of patients who received the low dose of Peg-IFN (P = NS). In patients with genotypes 1, 4 and 5 and low viraemia, SVR was obtained in 27.3% of patients treated with the standard dose and 25.8% of patients treated with the low dose (P = NS). In the high-viraemia subgroup, SVR was obtained in 24.0% and 9.1% of patients, respectively. In patients with genotypes 2 and 3, SVR was similar in both groups (73.2%vs 73.0%). Thus, (1) patients with genotypes 2 and 3 and severe fibrosis can be treated with low dose of Peg-IFN and ribavirin, (2) this study suggests that patients with genotypes 1, 4 and 5 and high viraemia could receive a standard dose of Peg-IFN associated with ribavirin for 48 weeks, (3) side effects limit the efficacy of the treatment with standard dose of Peg-IFN in patients with genotypes 1, 4 and 5 and low viraemia, (4) more studies are needed for patients with genotype 2 or 3 to define the optimal duration (24 or 48 weeks) in patients with severe fibrosis.     

Kinetics of hepatitis C virus RNA load during pegylated interferon plus ribavirin therapy in Treatment-naive Chinese patients

BACKGROUND/AIMS: To investigate the viral kinetics of Chinese CHC patients received pegylated interferon plus ribavirin and examine the impact of HCV genotypes and severity of liver disease. METHODOLOGY: 65 treatment-naove CHC patients who finished a 24-week therapy with peginterferon (alpha-2b (1.5 mcg/kg/week) plus ribavirin (1000-1200 mg /day) and 24 weeks of follow-up were enrolled. Hepatic fibrosis was graded by the METAVIR scoring system. Serum quantitative HCV RNA was determined by Versant HCV RNA 3.0 assay (Bayer Inc.). RESULTS: Genotype non-1 patients responded quickly and a higher percentage of them achieved undetectable HCV RNA (< 615 IU/mL) at week 4 compared with genotype 1 patients (93% vs. 69%, p = 0.018). Degree of hepatic fibrosis significantly affected end-of-treatment and sustained response (SVR). For patients who did not achieve early virological response (EVR), the negative predictive value for SVR was 100%. In genotype 1 patients, undetectable HCV RNA by week 4 was a good marker to predict treatment response, with a positive predictive value of 84% and a negative predictive value of 82%. CONCLUSIONS: EVR can be applied to Chinese patients as an early stopping rule. A 24-week duration of pegylated IFN/ribavirin might be adequate for genotype 1 patients who rapidly responded to therapy.     

Prospective study on early virologic response to treatment with interferon alpha-2b plus ribavirin in patients with chronic hepatitis C genotype 1b.

To evaluate the predictive value of early virologic response (EVR) of achieving a sustained virologic response (SVR), an open, prospective trial including 42 patients with chronic hepatitis C genotype 1b was performed with directly observed 24-week treatment with interferon alpha-2b plus ribavirin. We assessed the predictive values of EVR at days 3, 7, 14, and weeks 4, 8, and 12 of the SVR. The SVR in an intention-to-treat analysis was 19.0%. Patients who reached SVR presented a significantly faster reduction in plasma viral load. Stepwise multiple logistic regression analysis of the factors (gender, age, IFN dosage, ribavirin dosage, HCV RNA, ISDR, and loss of HCV RNA at week 4) revealed that loss of HCV RNA at week 4 was the only independent variable of treatment outcome (P=0.0039). A viral load at treatment day 3 above 100kIU/ml, at day 7 above 50kIU/ml, and at day 14 above 10kIU/ml was 100% predictive for virologic non-response in all except 1 patient. The cutoff levels for HCV RNA at days 3 and 14 of treatment were associated with an algorithm of the failure to detect HCV RNA after 12 weeks of treatment. In conclusions, a very early virologic response assessment could be useful for prediction of later outcome of combination therapy in chronic hepatitis C genotype 1b.     

Response-guided peginterferon-alpha-2b plus ribavirin therapy for chronic hepatitis C patients with genotype 2 and high viral loads

Aims: Optimization of the duration of peginterferon‐α/ribavirin therapy in patients with hepatitis C virus (HCV) genotype 2 and high viral loads remains to be established. We sought to prospectively optimize the treatment duration based on their virological responses. Methods: Serum HCV RNA levels of less than 50 IU/mL at weeks 2 and 4, and of 50 IU/mL or more at week 4, were defined as a super‐rapid virological response (SRVR), rapid virological response (RVR) and late virological response (LVR), respectively. Treatment for 12, 24 or 48 weeks was assigned to the patients with an SRVR, RVR or LVR, respectively. However, patients with an LVR who expressed a desire to receive the standard therapy duration were given the 24‐week therapy. Results: The overall sustained virological response (SVR) rate was 78.1% (118/151). The SVR rate in the SRVR group was 93.8% (15/16), which was comparable to the 93.0% (66/71) SVR rate in the RVR group. In the LVR patients, the 48‐week treatment slightly increased the SVR rate to 76.5% (13/17) compared with the 51.1% (24/47) SVR rate in LVR patients who underwent the standard 24‐week treatment. The relapse rate in LVR patients was significantly decreased in patients treated for 48 weeks compared with patients treated for 24 weeks. Multivariate analysis identified the predictive factors for SVR as RVR, prior interferon therapy and total peginterferon‐α‐2b adherence in patients treated for 24 weeks. Conclusion: Response‐guided therapy may be effective and useful for optimization of the treatment duration.