Acute hepatitis C: a 24-week course of pegylated interferon α-2b versus a 12-week course of pegylated interferon α-2b alone or with ribavirin.

UNLABELLED: Therapy of acute hepatitis C (AHC) has not yet been standardized and several issues are still unresolved. This open, randomized, multicenter trial aimed to assess the efficacy and safety of a 24-week course of pegylated IFN (Peg-IFN) alpha-2b versus a 12-week course of Peg-IFN alpha-2b alone or with ribavirin (RBV) in AHC patients. One hundred and thirty HCV acutely infected patients who did not spontaneously resolve by week 12 after onset were consecutively enrolled and randomized to receive Peg-IFN alpha-2b monotherapy (1.5 µg/kg/week) for 24 or 12 weeks (arm 1, n = 44 and arm 2, n = 43, respectively) or in combination with RBV (10.6 mg/kg/day) for 12 weeks (arm 3, n = 43). The primary endpoint was undetectable HCV RNA at 6-month posttreatment follow-up (sustained virological response; SVR). All patients were followed for 48 weeks after therapy cessation. HCV RNA levels were determined by real-time polymerase chain reaction (limit of detection: 15 IU/mL) at the central laboratory at baseline, week 4, end of treatment, and 6 and 12 months posttreatment. Using an intent-to-treat analysis, overall SVR rate was 71.5%. In particular, an SVR was achieved in 31 of 44 (70.5%), 31 of 43 (72.1%), and 31 of 43 (72.1%) patients in arms 1, 2, and 3, respectively (P = 0.898). Sixteen patients (12.3%) prematurely discontinued therapy or were lost to follow-up; thus, sustained response rates with per-protocol analysis were 81.6%, 81.6%, and 81.6% for patients in arms 1, 2, and 3 respectively. With multivariate analysis, virologic response at week 4 of treatment was an independent predictor of SVR. Peg-IFN alpha-2b was well tolerated. CONCLUSION: Peg-IFN alpha-2b induces a high SVR in chronically evolving AHC patients. Response rates were not influenced by combination therapy or treatment duration.

Real life experience in treatment of HIV-1/HCV-coinfected patients with pegylated interferon alpha and ribavirin: predictors of SVR.

Single nucleotide polymorphisms (SNPs) rs12979860 and rs8099917 near the interleukin 28B gene are predictors of virological response (SVR) to IFN-based therapy for monoinfected chronic hepatitis C patients. We retrospectively evaluated the impact of IL28B SNPs and other factors on SVR in a cohort of 102 HIV-1/HCV-coinfected patients treated with pegylated interferon-? (peg-INF?) and ribavirin. Data on baseline features and virological response at different time-points were collected. Overall, 89/102 patients (87%) were males, 44 (43%) of whom infected with HCV genotype 1; SVR was achieved by 50 patients (49%). A univariate logistic regression analysis demonstrated that rs129679860 SNP genotype CC (p<0.034), rs8099917 SNP genotype TT (p<0.01), HCV genotype 2 or 3 (p<0.0001), low HCV viral load (p<0.028) and RVR (rapid virological response) (p<0.0001) were associated with a higher likelihood of SVR. Multivariate analysis confirmed only RVR and HCV genotype as independent predictors of SVR. In a real life setting, the importance of RVR and IL28B SNPs was confirmed as predictive of SVR to identify patients with a higher likelihood of SVR to Peg-INF?+RBV, and also to designate a deferred therapy for patients with a low likelihood of SVR for whom it is preferable to wait for more successful options.

Early and sustained virological response in non-responders with chronic hepatitis C: a randomized open-label study of pegylated interferon-alpha-2a versus pegylated interferon-alpha-2b.

OBJECTIVES: The purpose of this randomized open-label study was to assess the efficacy of treatment with pegylated interferon-alpha-2a versus pegylated interferon-alpha-2b, both plus ribavirin, in inducing early and sustained virological response (EVR and SVR) in chronic hepatitis C non-responders. PATIENTS AND METHODS: A total of 108 patients with chronic hepatitis C who were non-responders to previous combined therapy (standard interferon-alpha plus ribavirin for > or = 3 months) were enrolled and equally randomized into two groups in this intention-to-treat analysis. The patients exhibited similar baseline features. One group received subcutaneous pegylated interferon-alpha-2a 180 microg once weekly, while the other was treated with subcutaneous pegylated interferon-alpha-2b 1.5 microg/kg once weekly. Ribavirin 15 mg/kg/day was included in both protocols. Treatment duration for EVR was 12 weeks. Patients who demonstrated non-detectable hepatitis C virus (HCV) RNA or a > or = 2 log(10) reduction in viral load at week 12 continued therapy up to 48 weeks, with assessments every 3 months during a follow-up of 24 weeks. RESULTS: All patients in both groups completed the EVR study, then seven patients receiving pegylated interferon-alpha-2a and seven patients receiving pegylated interferon-alpha2b discontinued treatment as a result of severe adverse effects. After 12 weeks of treatment, viral load reduction was >2 log(10) with both pegylated interferon-alpha-2a (-2.53) and pegylated interferon-alpha-2b (-2.48) with no significant difference. At the end of week 48, HCV RNA was undetectable in 14 of 54 patients (25.9%) receiving pegylated interferon-alpha-2a and in 15 of 54 patients (27.7%) receiving pegylated interferon-alpha-2b. When terminating follow-up, an SVR was observed in 11 of 54 patients (20.4%) who received pegylated interferon-alpha-2a and 10 of 54 patients (18.4%) receiving pegylated interferon-alpha-2b. The incidence and severity of adverse events was similar in both groups. CONCLUSIONS: Our results seem to show that in chronic hepatitis C patients who are non-responsive to previous therapy, EVR to the two pegylated interferons did not significantly differ with a similar therapeutic efficacy defined as SVR.

Treatment of genotype 1b HCV-related chronic hepatitis: efficacy and toxicity of three different interferon alfa-2b/ribavirin combined regimens in naive patients.

This prospective open-label randomized trial of chronic hepatitis C genotype-1b patients compared compared the efficacy and safety of peg-interferon alfa-2b administered once-weekly versus interferon alfa-2b thrice-weekly or daily, both in combination with ribavirin. Seventy-eight previously untreated patients, with biopsy-documented genotype 1 chronic HCV and persistently elevated ALT levels and detectable HCV RNA, were randomized (26 subjects each) to receive: interferon alfa-2b at 6MIUs.c./three-times-weekly (group A) or interferon alfa-2b, 3MIUs.c./daily (group B) or peg-interferon alfa-2b 1.5mcg/Kg s.c./once-weekly (group C). All regimens included standard weight-based doses of ribavirin (800, 1,000 or 1,200 mg/day) administered for 52-weeks. Patients in the three groups were comparable for age, sex, viral load, ALT value and histological-activity-index (HAI). Therapy was completed by 22, 20 and 23 patients in groups A, B and C, respectively. At the end of treatment, a complete (biochemical and virological) response was observed in 50.0% patients of group A, 57.7% of group B and 65.4% of group C. After an additional 24-weeks of follow-up, a sustained response was observed in 26.9%, 46.1% and 50.0% of patients in groups A, B or C, respectively. Therapy was discontinued by 4, 6 and 2 patients because of adverse events in the above three groups. In naive patients with chronic genotype-lb hepatitis C, a 48 week therapy with peg-interferon or interferon at daily doses combined with ribavirin were both more effective than treatment with thrice-weekly interferon in inducing end of treatment and sustained response. Peg-interferon treatment was better tolerated and provoked significantly fewer therapy discontinuations.

OPERA: use of pegylated interferon plus ribavirin for treating HCV-HIV coinfection in interferon-naive patients.

BACKGROUND: The Optimized Pegylated interferons Efficacy and anti-Retroviral Approach (OPERA) study aimed to assess the efficacy and safety profile of treatment with pegylated interferons (PEG-IFNs) in interferon-naive patients with chronic HCV and HIV infection in routine clinical practice. METHODS: This was a multicentre, prospective observational cohort study conducted at 98 Italian referral centres for the treatment of chronic HCV and HIV coinfection. Adult subjects (n=1,523) with a confirmed diagnosis of HCV and stable HIV coinfection were followed between April 2005 and March 2011; of these, 1,284 were interferon-naive and were the focus of this analysis. Patients received PEG-IFN-α2a or -α2b plus ribavirin combination therapy. The choice of treatment and dose was at the investigator's discretion, according to the summary of product characteristics and current guidelines. The primary efficacy end point was sustained virological response (SVR). Secondary end points included rates of rapid viral response, early viral response and response at end of treatment. RESULTS: SVR was achieved by 40.0% of patients; the highest SVR rate was observed in patients with HCV genotypes 2 and 3. More genotype 2 and 3 than genotype 1 and 4 patients achieved rapid and early viral responses, and end of treatment responses. Higher SVR rates were also associated with ≥80% anti-HCV treatment compliance and lower baseline HCV levels. CONCLUSIONS: The OPERA study results show that PEG-IFN plus ribavirin is an effective treatment for HCV-HIV coinfection in interferon-naive patients. Independent predictors of SVR include HCV genotype, undetectable baseline HIV RNA and baseline HCV RNA<500,000 IU/ml.

Peg-interferon alpha-2a versus Peg-interferon alpha-2b in nonresponders with HCV active chronic hepatitis: a pilot study.

BACKGROUND: The efficacy and tolerability of Peg-Interferon alpha-2a (Peg-IFNalpha-2a) versus Peg-Interferon alpha-2b (Peg-IFNalpha-2b) were compared in a patient cohort with hepatitis C virus (HCV)-related active chronic hepatitis, unresponsive to previous antiviral treatment with standard IFN (6 MU three times/week) plus ribavirin (10.6 mg/kg/day) for a period of at least 3 months. PATIENTS AND METHODS: A total of 143 patients were enrolled and randomized into two treatment groups (A-B). Group A (71 patients) received one vial of Peg-IFNalpha-2a weekly (180 microg) subcutaneously whereas Group B (72 patients) received 1.5 microg/kg of Peg-IFNalpha-2b weekly subcutaneously. Interferon was combined with ribavirin (15 mg/kg/day) in both groups and all patients who demonstrated nondetectable HCV-RNA or a >or=2(log) reduction in viral load at week 12, were treated for 48 weeks, with a 24-week follow up. RESULTS: Group A (10/71) and Group B (8/72) patients discontinued treatment due to severe side effects. At the end of therapy, HCV-RNA was undetectable in 17/71 (23.9%) Group A and in 19/72 (26.4%) of Group B patients. When terminating follow up, a sustained virological response was observed in 14/71 in Group A (19.7%) and 13/72 in Group B (18.0%). CONCLUSIONS: Within the limits of the relatively small sample size, Peg-IFNalpha-2a and Peg-IFNalpha-2b demonstrated nonstatistically significant differences in effectiveness in patients nonresponsive to previous antiviral treatment.