First phase viral kinetic parameters and prediction of response to interferon alpha-2b/ribavirin combination therapy in patients with chronic hepatitis C.

The aim of the present study was to assess parameters in early phase HCV dynamics for predicting the outcome of interferon (IFN)/ribavirin combination therapy in patients with chronic hepatitis C (CH-C). Sixty-five CH-C patients who received IFN alpha-2b/ribavirin combination therapy were enrolled. The serum levels of HCV RNA 0h and 3 months after commencing therapy were serially quantified. HCV kinetic parameters such as quantity, ratio of decline, and half-life were analyzed. In genotype 1 patients, both the quantity and the ratio of decline of HCV RNA 24h after the start of therapy were useful predictors of a poor response. No patients who had serum HCV RNA above 200KIU/ml 24h after the start of therapy achieved a sustained viral response (SVR). In genotype 2 patients, conversely, these two parameters were predictors of a sustained viral response. The efficacy of these parameters in predicting the outcome of therapy was comparable to that of the disappearance of HCV RNA from sera at 4 weeks. These results demonstrate that parameters of HCV kinetics 24h after the start of therapy are useful for the early prediction of outcome in response to IFN alpha-2b/ribavirin combination therapy.     

聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎患者疗效及其影响因素分析

目的：观察聚乙二醇干扰素（PEG IFNα-2a）联合利巴韦林（RBV）治疗慢性丙型肝炎（CHC）患者的疗效及其影响因素。方法对331例慢性丙型肝炎患者予 PEG IFNα-2a（180μg/w 或135μg/w）联合利巴韦林（RBV）900~1200 mg/d 抗病毒治疗,疗程48～72 w,随访24 w;治疗前检测丙型肝炎病毒基因型,采用 PCR 法检测丙型肝炎病毒（HCV）RNA 水平及肝功能,以病毒学应答和生化学应答作为疗效的主要评价指标。结果在331例CHC 患者中,获得快速病毒学应答率（RVR）、早期病毒学应答率（EVR）和持续病毒学应答率（SVR）分别为65%（215/331）、94.9%（314/331）和84.9%（281/331）;对176例行基因分型,结果108例基因1型与68例非1型感染者SVR 分别为88.0%和79.4%,两组比较无明显差异;75例血清 HCV RNA 水平小于4×105 IU/ml 的患者 SVR 为93.3%,高于256例 HCV RNA 水平大于4×105 IU/ml 患者的82.4%（P〈0.05）;215例获得 RVR 的 CHC 患者的SVR 明显高于116例未获得 RVR 患者（92.6%对70.7%,x2=28.099,P=0.000）,314例获得 EVR 患者的 SVR 也明显高于17例未获得 EVR 组（88.5%对17.6%,x2=63.194,P=0.000）;50例未获得 SVR 的 CHC 患者年龄和感染丙型肝炎病毒的时间分别为（46±15）岁和（14.8±8.0）年,显著大或长于281例获得 SVR 患者[（38±13）岁和（11.5±7.7）年,P 均〈0.05]。结论聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎疗效较好,预测临床疗效的关键因素是患者年龄、感染丙型肝炎的病程、治疗前 HCV RNA 水平及在治疗过程中能否及时获得 RVR 和 EVR。     

Reinforced interferon alpha-2b and ribavirin is more effective than standard combination therapy in the retreatment of chronic hepatitis C previously nonresponsive to interferon: a randomized trial

Interferon-alpha (IFN) monotherapy results in sustained virological clearance in a minority of patients with chronic hepatitis C. The aim of this study was to assess the effect of a reinforced regimen combining ribavirin and high-dose IFN for 48 weeks compared with a nonreinforced regimen combining a standard IFN regimen and ribavirin for 24 weeks in nonresponders with chronic hepatitis C. A total of 231 patients with chronic hepatitis C and previous nonresponse to IFN monotherapy were randomized. The reinforced group (n = 114) received IFN-2b 6 million units (MU) thrice weekly (TIW) and ribavirin for 48 weeks, and the nonreinforced group (n = 117) received IFN-2b 3 MU TIW and ribavirin for 24 weeks. The main outcome measure was a sustained virological response, defined as negative serum hepatitis C virus (HCV)-RNA 24 weeks following the end of treatment. This endpoint was determined in 98 patients of the reinforced group and 105 patients of the nonreinforced group. At the end of follow-up, a sustained virological response was observed in 29 of the 98 patients (29.6%) in the reinforced group vs 16 of the 105 patients (15.2%) in the nonreinforced group (P = 0.014). In multivariate analysis, factors associated with a sustained virological response were treated with a reinforced regimen [odds ratio (OR) 2.9; P = 0.06] and genotype 2 or 3 (OR 8.8; P < 0.0002). A total of 160 patients had paired biopsies before and after treatment. Histological activity improvement was observed in 32 of 80 patients (40%) and fibrosis worsening in 26 of 80 patients (33%) in the reinforced group vs 13 of 80 (16%) and 19 of 80 (24%) in the nonreinforced group (P = 0.30 and 0.20, respectively). Hence in nonresponders, a high-dose 48-week regimen of IFN and ribavirin combination was more effective than a regimen with interferon at lower dose and ribavirin for 24 weeks only.     

Impact of early viral kinetics on pegylated interferon alpha 2b plus ribavirin therapy in Japanese patients with genotype 2 chronic hepatitis C

Summary. The recommended therapy for genotype‐2 chronic hepatitis C is a regimen of pegylated interferon alpha (peginterferon) plus ribavirin. This study was conducted to determine the value of early viral kinetics as a predictive factor for sustained virologic responder (SVR). Peginterferon alpha 2b (1.5 μg/kg/week) plus weight‐based ribavirin (600–1000 mg/day) was administered to 51 patients with chronic HCV genotype 2 for 24 weeks. The HCV‐RNA loads were measured at the baseline, hour 24, and week 1. The rebound index (RI, an index obtained from the viral load of week 1 divided by that of hour 24) was calculated. Compared with the baseline, the viral load at hour 24 for SVR was reduced by more than 1‐log: it continued to decline thereafter, and at week 1 it was significantly lower than at hour 24 (P < 0.05). The viral load for non‐SVR increased again between hour 24 and week 1. The SVR of patients with RI ≤1.0 was 100% (39/39). The SVR conversion for rapid virologic responders was 92% (35/38). The RI (≤1.0) was the only significant independent factor for SVR by multiple logistic regression analysis and is the first predictive factor in 24‐week peginterferon plus ribavirin therapy for patients infected with genotype 2.     

Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotype 1b and high viral load

Background

This study explores pretreatment predictive factors for ultimate virological responses to pegylated interferon-α (1.5?μg/kg/week) and ribavirin (600–1000?mg/day) (PEG-IFN/RBV) combination therapy for patients infected with hepatitis C virus (HCV)-1b and a high viral load.

Methods

A total of 75 patients underwent PEG-IFN/RBV combination therapy for 48?weeks. HCV amino acid (aa) substitutions in non-structural protein 5a, including those in the IFN/RBV resistance-determining region (IRRDR) and the IFN sensitivity-determining region and the core regions, as well as the genetic variation (rs8099917) near the interleukin 28B (IL28B) gene (genotype TT) were analyzed.

Results

Of the 75 patients, 49?% (37/75) achieved a sustained virological response (SVR), 27?% (20/75) showed relapse, and 24?% (18/75) showed null virological response (NVR). Multivariate logistic regression analysis identified IRRDR with 6 or more mutations (IRRDR ≥6) [odds ratio (OR) 11.906, p?<?0.0001] and age <60?years (OR 0.228, p?=?0.015) as significant determiners of SVR and IL28B minor (OR 14.618, p?=?0.0019) and platelets <15?×?10⁴/mm³ (OR 0.113, p?=?0.0096) as significant determiners of NVR. A combination of IRRDR ≥6 and age <60?years improved SVR predictability (93.3?%), and that of IRRDR ≤5 and age ≥60?years improved non-SVR predictability (84.0?%). Similarly, a combination of IL28B minor and platelets <15?×?10⁴/mm³ improved NVR predictability (85.7?%), and that of IL28B major and platelets ≥15?×?10⁴/mm³ improved non-NVR (response) (97.1?%) predictability.

Conclusion

IRRDR ≥6 and age <60?years were significantly associated with SVR. IL28B minor and platelets <15?×?10⁴/mm³ were significantly associated with NVR. Certain combinations of these factors improved SVR and NVR predictability and could, therefore, be used to design therapeutic strategies.     

Risk factors for retinopathy associated with interferon α-2b and ribavirin combination therapy in patients with chronic hepatitis C

AIM: To elucidate the frequency and risk factors for retinopathy in patients with chronic hepatitis C who are treated by interferon-ribavirin combination therapy. METHODS: We prospectively analyzed 73 patients with histologically confirmed chronic hepatitis C, who underwent combination therapy for 24 wk. Optic fundi were examined before, and 2, 4, 12 and 24 wk after the start of combination therapy. RESULTS: Fourteen patients (19%) developed retinopathy, which was initially diagnosed by the appearance of a cotton wool spot in 12 patients. Retinal hemorrhage was observed in 5 patients. No patient complained of visual disturbance. Retinopathy disappeared in 9 patients (64%) despite the continuation of combination therapy. However, retinopathy persisted in 5 patients with retinal hemorrhage. A comparison of the clinical background between the groups with and without retinopathy showed no significant differences in age, gender, viral genotype, RNA level, white blood cell count, platelet count, prothrombin time, complications by diabetes mellitus or hypertension, or pretreatment arteriosclerotic changes in the optic fundi. However, multiple logistic regression analysis revealed that complication by hypertension was observed with a high frequency in the group with retinopathy (P = 0.004, OR = 245.918, 95% CI = 5.6-10786.2). CONCLUSION: Retinopathy associated with combination therapy of interferon alpha-2b and ribavirin tends to develop in patients with hypertension.     

Twenty-four weeks of interferon alpha-2b in combination with ribavirin for Japanese hepatitis C patients: sufficient treatment period for patients with genotype 2 but not for patients with genotype 1.

BACKGROUND: Hepatitis C virus (HCV) RNA titer and HCV genotype are two major determinants of the outcome of interferon (IFN) monotherapy. To clarify the usefulness of combination therapy with IFN and ribavirin in Japanese hepatitis C patients, we treated patients with a relatively high dose of IFN in combination with ribavirin for 24 weeks and examined the effects in relation to the viral parameters. METHODS: Two hundred and ninety-five patients were enrolled in the study. The patients received either 6 or 10 million units (MU) of interferon alpha-2b every day for 2 weeks and then three times a week for 22 weeks with a daily dose of either 600 or 800 mg of ribavirin. The treatment response and safety of this treatment were examined. RESULTS: The sustained virologic response (SVR) rates were 26.8% in genotype 1 and 76.5% in genotype 2 (P < 0.001), and 36.1% with the 6 MU group and 45.8% with the 10 MU group (P = 0.09). Multivariate analysis indicated that SVR was associated with genotype 2, HCV RNA <500 kilointernational unit/ml (kIU/ml), and HCV RNA undetectability at week 8 of treatment. CONCLUSION: Our current study showed that a 24-week course of IFN plus ribavirin combination therapy was effective with respect to virologic response in Japanese hepatitis C patients, particularly in patients with HCV genotype 2.     

聚乙二醇干扰素加利巴韦林治疗慢性丙型肝炎疗效影响因素分析

目的研究聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎（丙肝）疗效的影响因素。方法101例慢性丙肝患者均给予聚乙二醇干扰素α-2a 180μg／周联合利巴韦林10．6～15．0mg／（kg·d）,疗程48周,分析性别、体重指数（body mass index,BMI）、初始HCVRNA定量、ALT及GLU等对持续病毒学应答（sustainedvirologicresponse,SVR）的影响。结果聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙肝总的SVR率为50％,其中获得快速病毒学应答（rapid virologic response．RVR）和早期病毒学应答（early virologic response,EVR）患者实现SVR达100％,未获得RVR和EVR患者实现SVR为19．35％;高BMI值、发生脂肪肝的患者不容易达到SVR,而糖化血红蛋白、初始HCVRNA载量高、GLU、ALT及性别对SVR无影响。结论RVR、EVR可以预测SVR;BMI、是否合并脂肪肝是聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙肝获得SVR的影响因素。     

普通干扰素1b联合利巴韦林治疗非1b型慢性丙型肝炎患者临床观察

目的探讨不同基因型HCV感染者对普通干扰素联合利巴韦林治疗的疗效。方法应用型特异性探针杂交法检测106例慢性丙型肝炎患者HCV基因型。应用普通干扰素联合利巴韦林治疗,观察病毒学应答情况。结果在106例患者中,以HCV 3b（45.3%）、1b（20.8%）和3a（18.9%）型为主,6a（9.4%）和2a（5.7%）型次之;在22例1b型感染者,只有9例接受本治疗方案,82例非1b型感染者完成治疗。非1b型患者的RVR和EVR分别为50%和86.6%;在1b型HCV感染者,22.2%（2/9）获得SVR,而非1b型HCV感染者,76.8%（63/82）获得SVR。结论普通干扰素联合利巴韦林治疗非1b型慢性丙型肝炎患者疗效较好。     

Ribavirin dose reduction raises relapse rate dose-dependently in genotype 1 patients with hepatitis C responding to pegylated interferon alpha-2b plus ribavirin

Summary.  The impact of ribavirin exposure on virologic relapse remains controversial in combination therapy with pegylated interferon (Peg-IFN) and ribavirin for patients with chronic hepatitis C (CH-C) genotype 1. The present study was conducted to investigate this. Nine hundred and eighty-four patients with CH-C genotype 1 were enrolled. The drug exposure of each medication was calculated by averaging the dose actually taken. For the 472 patients who were HCV RNA negative at week 24 and week 48, multivariate logistic regression analysis showed that the degree of fibrosis ( P  =   0.002), the timing of HCV RNA negativiation ( P  <   0.001) and the mean doses of ribavirin ( P  <   0.001) were significantly associated with relapse, but those of Peg-IFN were not. Stepwise reduction of the ribavirin dose was associated with a stepwise increase in relapse rate from 11% to 60%. For patients with complete early virologic response (c-EVR) defined as HCV RNA negativity at week 12, only 4% relapse was found in patients given ≥12 mg/kg/day of ribavirin and ribavirin exposure affected the relapse even after treatment week 12, while Peg-IFN could be reduced to 0.6 μg/kg/week after week 12 without the increase of relapse rate. Ribavirin showed dose-dependent correlation with the relapse. Maintaining as high a ribavirin dose as possible (≥12 mg/kg/day) during the full treatment period can lead to suppression of the relapse in HCV genotype 1 patients responding to Peg-IFN alpha-2b plus ribavirin, especially in c-EVR patients.     

Safety and efficacy of treatment with pegylated interferon alpha-2a with ribavirin in chronic hepatitis C genotype 4

The hepatitis C virus (HCV) genotype is an important predictive outcome parameter for pegylated interferon plus ribavirin therapy. Most published therapeutic trials to date have enrolled mainly patients with HCV genotypes 1, 2 and 3. Limited studies have focused on genotype 4 patients, who have had a poor representation in pivotal trials. Our aim was to evaluate the efficacy and safety of treatment with standard dose pegylated interferon alfa-2a in combination with weight-based ribavirin in patients with chronic hepatitis C genotype 4. In this prospective observational study, 198 patients with HCV-4 were included in this study from February 2004 to August 2005,188 patients who received at least 1 dose of drugs were included in the ITT analysis and they were treated with pegylated interferon alfa-2a and ribavirin for 48 weeks. Baseline and demographic characteristics, response to treatment at weeks 12, 48 and 72, and the nature and frequency of adverse effects were analyzed. Virological response at week 12 was achieved in 144 patients (76.6%). Virological response at the end of treatment was present in 110 patients (58.5%). At week 72, 99 patients presented SVR (52.7%). The reported adverse events were similar to those found in the literature for treatments of similar dose and duration. In conclusion, combined treatment with pegylated interferon alfa-2a and ribavirin was well tolerated and effective in chronic hepatitis C genotype 4, yielding response rates between those reported for genotype 1 and those of genotypes 2-3.     

Short-term prolongation of pegylated interferon and ribavirin therapy for genotype 1b chronic hepatitis C patients with early viral response

Aim:  We tailored extended treatments using pegylated interferon (PEG IFN) and ribavirin (RBV) to viral responses after initiation of therapy and investigated the efficacy and safety of its therapy for chronic hepatitis C (CHC) patients.
Methods:  Eighty-two genotype 1b CHC patients were enrolled in the present study. All patients received PEG IFN-α-2b and weight-based RBV therapy. We defined a viral response in which serum HCV-RNA is undetectable at week 4 as rapid viral response (RVR), detectable at week 4 and undetectable by week 12 as early viral response (EVR), and detectable at week 12 and undetectable by week 24 as late viral response (LVR). We set the treatment duration depending on viral response; 48 weeks for RVR patients and 72 weeks for LVR. Furthermore, EVR patients received a short-term extension of treatment duration to 52–60 weeks. We prospectively investigated sustained viral response (SVR) rates of these groups.
Results:  Overall SVR rate for the total patient group was 57.3%. SVR rates of the RVR, EVR and LVR patients were 100%, 80.5% and 40.0%, respectively. Nine patients could not complete this treatment protocol. Baseline platelet count and mutation in the interferon sensitivity-determining region of NS5A were significant independent predictors of SVR, and amino acid substitution of the core region was a significant independent predictor of non-viral response by multivariate logistic regression analyses.
Conclusion:  The results indicate that short-treatment extension of PEG IFN plus RBV treatment protocols in EVR patients can improve overall SVR rates.     

Response to pegylated interferon plus ribavirin in HIV-infected patients with chronic hepatitis C due to genotype 4

SUMMARY: Hepatitis C virus (HCV) genotypes 1 and 4 respond less well to pegylated interferon (pegIFN) plus ribavirin (RBV) therapy. For this reason most studies merge these two genotypes when assessing virological response. However, in most trials the HCV genotype 4 population is rather small, and conclusions are mainly derived from what occurs in HCV-1 patients. All HCV-4 patients coinfected with HIV who received pegIFN plus RBV in two different multicentre studies, PRESCO and ROMANCE, conducted respectively in Spain and Italy, were retrospectively analyzed. Baseline plasma HCV-RNA, proportion of patients with HCV-RNA <10 IU / mL at week 4 (rapid virological response), and HCV-RNA declines >2 logs at week 12 (early virological response, EVR) were all assessed as predictors of sustained virological response (SVR). Overall, 75 patients (60 men) were evaluated. Median age was 40 years and median CD4 count 598 cells / mm(3); 49% had plasma HIV-RNA <50 copies / mL; 71% had elevated liver enzymes and 31% had advanced liver fibrosis (Metavir F3-F4). Median serum HCV-RNA was 5.7 log IU / mL. Rapid virological response was attained by 10 (20%) patients and EVR by 26 (42%). Using intention-to-treat and on-treatment (OT) analyses, SVR was achieved by 21 / 75 (28%) and 21 / 62 (34%) of HCV-4 patients, respectively. In the multivariate analysis (OT), baseline HCV-RNA (OR 0.09 for every log increment; 95% CI: 0.01-0.7) and EVR (OR: 7.08; 95% CI: 1.8-27.2) were significantly and independently associated with SVR. This is the largest series of HIV-infected patients with chronic hepatitis C due to HCV-4 treated with pegIFN plus RBV examined so far and the results show that HCV-4 behaves similarly to HCV-1. Therefore, these patients should be considered as difficult to treat population. Baseline serum HCV-RNA and EVR are the best predictors of SVR in HCV-4 / HIV-coinfected patients.     

Chronic hepatitis C genotype 6 responds better to pegylated interferon and ribavirin combination therapy than genotype 1

Background and Aims: Chronic hepatitis C genotype 6 is common in Hong Kong, especially among i.v. drug abusers. Responses of these patients to combination of pegylated interferon and ribavirin treatment were inconsistent and the numbers of patients involved in previous studies were small. We performed a retrospective study to compare the therapeutic responses of this regimen in patients infected with genotype 6 and genotype 1. Methods: Seventy patients with either genotype 6 or genotype 1 were recruited. Both groups received 800–1200 mg of ribavirin daily plus either 180 mg of pegylated α‐interferon‐2a or 1.5 mg/kg pegylated α‐interferon‐2b weekly for 48 weeks. Their responses to treatments were compared. Results: The early virological response to combination therapy of patients with genotype 6 was significantly better than that of genotype 1 (88.6% vs 74.3%, P = 0.03). Significant difference was also identified in the end of treatment response of the two genotypes (60% vs 81.4% for genotype 1 and 6, respectively; P = 0.005). The sustained virological response (SVR) to treatment in patients with genotype 6 was also significantly superior to that of patients with genotype 1 (75.7% vs 57.1%, P = 0.02). Multiple logistic regression analysis demonstrated that age of 55 years or less, genotypes of hepatitis C virus, liver biopsy staging and baseline hepatitis C virus RNA of 200 000 IU/mL or less were independent predictors for better SVR in this cohort. Conclusion: Patients with chronic hepatitis C genotype 6 respond better to pegylated interferon and ribavirin combination treatment than patients with genotype 1.     

Peginterferon alpha-2b plus ribavirin vs interferon alpha-2b plus ribavirin for chronic hepatitis C in HIV-coinfected patients

Treatment of chronic hepatitis C in human immunodeficiency virus (HIV)-infected patients is associated with low response rates and high incidence of side effects. One hundred twenty-one hepatitis C virus (HCV)-HIV-coinfected patients were randomized to receive interferon alpha-2b (3 MU thrice weekly; n = 61) or peginterferon alpha-2b (1.5 microg/kg/week; n = 60), plus ribavirin (800 mg daily), for 24 (genotype 2 or 3) or 48 weeks (genotype 1 or 4). We assessed early virological response at 4, 8 and 12 weeks to predict sustained virological response (SVR). Safety assessment included frequent blood lactate measurement and relative quantitation of mitochondrial DNA (mtDNA) content in peripheral blood mononuclear cells. In intention-to-treat analysis, the SVR rate was higher in the peginterferon group (55%vs 26%; P = 0.002). The difference for HCV genotypes 1 and 4 was 45%vs 14% (P = 0.009) and 50%vs 27% (P = 0.387), respectively, and for genotype 2 or 3, 71%vs 43% (P = 0.12) Viral response at 4, 8 and 12 weeks of treatment was highly predictive of SVR. Among genotype 3 patients, 17 of 20 (85%) whose HCV RNA was already undetectable at 4 weeks had an SVR after 24 weeks of treatment. Hyperlactataemia occurred in 22 patients and was clinically significant in six, two of whom died. mtDNA decreased significantly 4-12 weeks after the start of treatment in patients developing clinically significant hyperlactataemia. Peginterferon alpha-2b plus ribavirin was more effective than interferon alpha-2b plus ribavirin in HIV-coinfected patients. Frequent monitoring of virological response may be very helpful to optimize treatment compliance, to tailor treatment duration and to minimize side effects.     

High-dose interferon alpha-2b induction therapy in combination with ribavirin for Japanese patients infected with hepatitis C virus genotype 1b with a high baseline viral load

Background Although pegylated interferon (IFN) is now used in many countries as a standard therapy for chronic hepatitis C, the efficacy and safety of combination therapy of high-dose interferon alpha-2b induction with ribavirin are not fully evaluated, especially in Japanese patients infected with hepatitis C virus (HCV) genotype 1b with a high viral load.Methods Patients (n = 83) received daily, high-dose induction therapy of interferon alpha-2b (6 million units [MU] once daily for 2 weeks), followed by 6MU three times weekly for 22 weeks. Oral ribavirin (800 or 600mg/day) was given daily for 24 weeks, and then the patients were followed up for 24 weeks.Results Of the 83 patients, 67 (81%) had a biochemical response (BR), and 37 (45%) achieved a sustained BR (SBR). Virologic response (VR; undetectable serum HCV RNA level by polymerase chain reaction [PCR]) was noted in 55 (66%) patients, and sustained VR (SVR) in 16 (19%) patients. Baseline viral load did not influence treatment outcome. There was no significant difference in treatment outcome among treatment-naÏve patients, relapsers, and nonresponders to previous IFN monotherapy. Multivariate analyses identified serum ribavirin concentrations at week 8 of therapy (odds ratio [OR], 23.7; 95% confidence interval [CI], 1.84–61.1; P = 0.015) and negativity for serum HCV RNA at week 8 (OR, 22.5; CI, 1.76–57.5; P = 0.017, respectively) as two significant and independent predictors of SVR.Conclusions The efficacy of 24-week combination therapy of high-dose IFN alpha-2b induction and ribavirin deserves attention in HCV genotype 1b patients with a high viral load, especially in nonresponders to previous IFN monotherapy and patients with a very high viral load.