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Janice K Albrecht - One of the best experts on this subject based on the ideXlab platform.

  • Peginterferon alfa 2b plus ribavirin for treatment of chronic hepatitis c in previously untreated patients infected with hcv genotypes 2 or 3
    2004
    Co-Authors: Stefan Zeuzem, Joann Harvey, Tobias Goeser, Patrick Marcellin, Jose Ma Sancheztapias, Rolf Hultcrantz, Marc Bourliere, Christoph Sarrazin, Clifford A Brass, Janice K Albrecht
    Abstract:

    Abstract Background/Aims Treatment duration in patients with chronic hepatitis C in the era of standard interferon-α 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-α plus ribavirin. Methods Patients chronically infected with HCV-2 ( n =42) or HCV-3 ( n =182) were treated with Peginterferon Alfa-2b 1.5 μg/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 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.

  • early virologic response to treatment with Peginterferon alfa 2b plus ribavirin in patients with chronic hepatitis c
    2003
    Co-Authors: L Gary M D Davis, Joann Harvey, John G Mchutchison, Michael P Manns, John B Wong, Janice K Albrecht
    Abstract:

    Interferon-based regimens for the treatment of chronic hepatitis C have become increasingly effective and are able to eradicate virus in more than one half of cases. Early identification of patients who will not respond is desirable because treatment might be stopped, thereby avoiding the expense and inconvenience of unnecessary therapy. We examined the accuracy of different degrees of viral inhibition during the early weeks of treatment (early virologic response [EVR]) with pegylated interferon Alfa-2b and ribavirin (PEG/R) in identifying patients who would not respond to therapy. The best definition of EVR was a reduction in hepatitis C virus (HCV) RNA by at least 2 logs after the first 12 weeks of treatment compared with baseline. Between 69% and 76% of patients achieved this threshold, depending on the treatment regimen, and sustained virologic response (SVR) occurred in 67% to 80% of these patients. Patients who did not reach EVR did not respond to further therapy. If treatment had been stopped in patients without EVR, drug costs would have been reduced by more than 20%. In conclusion, early confirmation of viral reduction following initiation of antiviral therapy for chronic hepatitis C is worthwhile. It provides a goal to motivate adherence during the first months of therapy and a milepost at which to reassess the need for continued treatment. Most patients who are able to complete the first 12 weeks of therapy achieve EVR and have a high probability of SVR. Patients who fail to achieve EVR will not clear virus even if an additional 9 months of therapy is received. Therapy can be confidently discontinued in those cases.

  • biochemical surrogate markers of liver fibrosis and activity in a randomized trial of Peginterferon alfa 2b and ribavirin
    2003
    Co-Authors: Thierry Poynard, John G Mchutchison, Michael Manns, R Myers, Janice K Albrecht
    Abstract:

    Liver fibrosis and activity indexes were validated in patients infected by hepatitis C virus (HCV) nontreated and treated by interferon. The aim was to validate their usefulness as surrogate markers of histologic features using the data of a randomized trial of combination Peginterferon Alfa-2b and ribavirin. Three hundred fifty-two patients who had had 2 interpretable liver biopsies and stored serum sample before and after treatment were selected. Two hundred eight patients received Peginterferon Alfa-2b 1.5 mcg per kg and ribavirin and 144 patients interferon Alfa-2b 3 MU three times a week and ribavirin for 48 weeks. A fibrosis and an activity index combining 5 and 6 biochemical markers were assessed at baseline and at end of follow-up (24 weeks after treatment). The biochemical markers have significant predictive values both for the diagnosis of fibrosis and for activity. For the diagnosis of bridging fibrosis and/or moderate necroinflammatory activity, the area under the receiver operating characteristics curve of the activity index was 0.76 +/- 0.03 at baseline and 0.82 +/- 0.02 at end of follow-up. A cutoff of activity index at 0.30 (range, 0.00-1.00) had 90% sensitivity and 88% positive predictive value for the diagnosis of bridging fibrosis or moderate necroinflammatory activity. Sensitivity analyses with biopsy specimens of size greater than 15 mm suggest that a part of discordances between biochemical markers and histology were due to biopsy specimen sampling error. In conclusion, these biochemical markers of fibrosis and activity could be used as surrogate markers for liver biopsy in patients with chronic hepatitis C, both for the initial evaluation and for follow-up.

  • Peginterferon alfa 2b plus ribavirin compared with interferon alfa 2b plus ribavirin for initial treatment of chronic hepatitis c a randomised trial
    2001
    Co-Authors: Michael P Manns, Meihsiu Ling, Vinod K Rustgi, Stuart C. Gordon, Mitchell L Shiffman, Zachary Goodman, John G Mchutchison, Robert Reindollar, Kenneth Koury, Janice K Albrecht
    Abstract:

    Summary Background A sustained virological response (SVR) rate of 41% has been achieved with interferon Alfa-2b plus ribavirin therapy of chronic hepatitis C. In this randomised trial, Peginterferon Alfa-2b plus ribavirin was compared with interferon Alfa-2b plus ribavirin. Methods 1530 patients with chronic hepatitis C were assigned interferon Alfa-2b (3 MU subcutaneously three times per week) plus ribavirin 1000–1200 mg/day orally, Peginterferon Alfa-2b 15 μg/kg each week plus 800 mg/day ribavirin, or Peginterferon Alfa-2b 1·5 μg/kg per week for 4 weeks then 0·5 μg/kg per week plus ribavirin 1000–1200 mg/day for 48 weeks. The primary endpoint was the SVR rate (undetectable hepatitis C virus [HCV] RNA in serum at 24-week follow-up). Analyses were based on patients who received at least one dose of study medication. Findings The SVR rate was significantly higher (p=0·01 for both comparisons) in the higher-dose Peginterferon group (274/511 [54%]) than in the lower-dose Peginterferon (244/514 [47%]) or interferon (235/505 [47%]) groups. Among patients with HCV genotype 1 infection, the corresponding SVR rates were 42% (145/348), 34% (118/349), and 33% (114/343). The rate for patients with genotype 2 and 3 infections was about 80% for all treatment groups. Secondary analyses identified bodyweight as an important predictor of SVR, prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight (mg/kg). Side-effect profiles were similar between the treatment groups. Interpretation In patients with chronic hepatitis C, the most effective therapy is the combination of Peginterferon Alfa-2b 1·5 μg/kg per week plus ribavirin. The benefit is mostly achieved in patients with HCV genotype 1 infections.

  • a randomized double blind trial comparing pegylated interferon alfa 2b to interferon alfa 2b as initial treatment for chronic hepatitis c
    2001
    Co-Authors: Karen L Lindsay, Mark A. Laughlin, Christian Trepo, Stuart C. Gordon, John C. Hoefs, Mitchell L Shiffman, Tobias Heintges, Eugene R Schiff, Zachary Goodman, Janice K Albrecht
    Abstract:

    Abstract This international, randomized, active-controlled, parallel-group, double-blind dose-finding study compared Peginterferon Alfa-2b (PegIntron™) to interferon Alfa-2b for the initial treatment of compensated chronic hepatitis C. We randomly assigned 1,219 subjects to receive either the standard three-times-weekly (TIW) interferon Alfa-2b dose (3 MIU) or the once-weekly (QW) Peginterferon Alfa-2b (0.5, 1.0, or 1.5 μg/kg). Subjects were treated for 48 weeks and then followed for an additional 24 weeks. All 3 Peginterferon Alfa-2b doses significantly ( P ≤ .042) improved virologic response rates (loss of detectable serum HCV RNA) after treatment and after follow-up, as compared with interferon Alfa-2b. Unlike the end-of-treatment virologic response, the sustained virologic response rate was not dose-related above 1.0 μg/kg Peginterferon Alfa-2b because of a higher relapse rate among patients treated with 1.5 μg/kg Peginterferon Alfa-2b, particularly among patients infected with genotype 1. All 3 Peginterferon Alfa-2b doses decreased liver inflammation to a greater extent than did interferon Alfa-2b, particularly in subjects with sustained responses. No new adverse events were reported, and the majority of adverse events and changes in laboratory values were mild or moderate. In conclusion, Peginterferon Alfa-2b maintained (0.5 μg/kg) or surpassed (1.0, 1.5 μg/kg) the clinical efficacy of interferon Alfa-2b while preserving its safety profile. The higher rate of virologic response during treatment with 1.5 μg/kg Peginterferon Alfa-2b in patients infected with genotype 1 and high viral levels warrants further evaluation. (H EPATOLOGY 2001;34:395-403.)

Eugene R Schiff - One of the best experts on this subject based on the ideXlab platform.

  • maintenance therapy with Peginterferon alfa 2b does not prevent hepatocellular carcinoma in cirrhotic patients with chronic hepatitis c
    2011
    Co-Authors: Jordi Bruix, Eugene R Schiff, Thomas Berg, Thierry Poynard, Massimo Colombo, Kelly W Burak, Elizabeth J Heathcote, J L Poo, Carlos Brandao Mello, Rainer Guenther
    Abstract:

    Background & Aims Several studies have reported that low doses of interferon can delay the development of hepatocellular carcinoma (HCC) and progression of chronic hepatitis C. We investigated the incidence of clinical events among participants of the Evaluation of PegIntron in Control of Hepatitis C Cirrhosis (EPIC) 3 program. Methods Data were analyzed from an open-label randomized study of patients with chronic hepatitis C who had failed to respond to interferon alfa plus ribavirin. All patients had compensated cirrhosis with no evidence of HCC. Patients received Peginterferon Alfa-2b (0.5 μg/kg/week; n=311) or no treatment (controls, n=315) for a maximum period of 5 years or until 98 patients had a clinical event (hepatic decompensation, HCC, death, or liver transplantation). The primary measure of efficacy was time until the first clinical event. Results There was no significant difference in time to first clinical event among patients who received Peginterferon Alfa-2b compared with controls (hazard ratio [HR], 1.452; 95% confidence interval [CI]: 0.880–2.396). There was no decrease in the development of HCC with therapy. The time to disease progression (clinical events or new or enlarged varices) was significantly longer for patients who received Peginterferon Alfa-2b compared with controls (HR, 1.564; 95% CI: 1.130–2.166). In a prospectively defined subanalysis of patients with baseline portal hypertension, Peginterferon Alfa-2b significantly increased the time to first clinical event compared with controls ( P = .016). There were no new safety observations. Conclusions Maintenance therapy with Peginterferon Alfa-2b is not warranted in all patients and does not prevent HCC. However, there is a potential clinical benefit of long-term suppressive therapy in patients with preexisting portal hypertension.

  • Peginterferon alfa 2b or alfa 2a with ribavirin for treatment of hepatitis c infection
    2009
    Co-Authors: John G Mchutchison, Jonathan Mccone, Eric Lawitz, Reem Ghalib, L. Nyberg, Andrew J. Muir, Mitchell L Shiffman, Eugene R Schiff, Greg Galler, Joseph S Galati
    Abstract:

    Background 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. Methods 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 μg per kilogram of body weight per week or a low dose of 1.0 μg 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 μg 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 alfa2b regimen and the Peginterferon alfa-2a regimen. Results 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 standarddose 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 peg interferon 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 lowdose Peginterferon Alfa-2b, and 31.5% (95% CI, 27.9 to 35.2) for Peginterferon alfa2a. 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. Conclusions 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. (ClinicalTrials. gov number, NCT00081770.)

  • Peginterferon alfa 2b and ribavirin effective in patients with hepatitis c who failed interferon alfa ribavirin therapy
    2009
    Co-Authors: Thierry Poynard, Eugene R Schiff, Jordi Bruix, Massimo Colombo, R Terg, Steven L Flamm, Ricardo Morenootero, Flair Jose Carrilho, W Schmidt, Thomas Berg
    Abstract:

    Background & Aims Treatment with Peginterferon alfa and ribavirin produces a sustained virologic response (SVR) in approximately 60% of hepatitis C virus (HCV)-infected patients. Alternate options are needed for patients who relapse or do not respond to therapy. Methods This prospective, international, multicenter, open-label study evaluated efficacy and safety of Peginterferon Alfa-2b (1.5 μg/kg/wk) plus weight-based ribavirin (800–1400 mg/day) in 2333 chronic HCV-infected patients with significant fibrosis/cirrhosis whose previous interferon alfa/ribavirin therapy failed. Patients with undetectable HCV-RNA at treatment week (TW) 12 received 48 weeks of therapy; patients with detectable HCV-RNA at TW12 could enter maintenance studies at TW18; 188 patients with low/detectable HCV-RNA at TW12 continued therapy at the investigator's request. Results Overall, 22% of the patients attained SVR (56% with undetectable HCV-RNA and 12% with low/detectable HCV-RNA at TW12). SVR was better in relapsers (38%) than nonresponders (14%), regardless of previous treatment, and in patients previously treated with interferon-alfa/ribavirin (25%) than Peginterferon alfa-ribavirin (17%). Predictors of response in patients with undetectable HCV-RNA at TW12 were genotype (2/3 vs 1, respectively; odds ratio [OR] 2.4; P P 600,000 IU/mL; OR, 1.4; P = .0223). These factors plus previous treatment and response were overall predictors of SVR. Safety was similar among fibrosis groups. Conclusions Peginterferon Alfa-2b plus weight-based ribavirin is effective and safe in patients who failed interferon alfa/ribavirin therapy. Genotype, baseline viral load, and fibrosis stage were predictors of response.

  • a randomized double blind trial comparing pegylated interferon alfa 2b to interferon alfa 2b as initial treatment for chronic hepatitis c
    2001
    Co-Authors: Karen L Lindsay, Mark A. Laughlin, Christian Trepo, Stuart C. Gordon, John C. Hoefs, Mitchell L Shiffman, Tobias Heintges, Eugene R Schiff, Zachary Goodman, Janice K Albrecht
    Abstract:

    Abstract This international, randomized, active-controlled, parallel-group, double-blind dose-finding study compared Peginterferon Alfa-2b (PegIntron™) to interferon Alfa-2b for the initial treatment of compensated chronic hepatitis C. We randomly assigned 1,219 subjects to receive either the standard three-times-weekly (TIW) interferon Alfa-2b dose (3 MIU) or the once-weekly (QW) Peginterferon Alfa-2b (0.5, 1.0, or 1.5 μg/kg). Subjects were treated for 48 weeks and then followed for an additional 24 weeks. All 3 Peginterferon Alfa-2b doses significantly ( P ≤ .042) improved virologic response rates (loss of detectable serum HCV RNA) after treatment and after follow-up, as compared with interferon Alfa-2b. Unlike the end-of-treatment virologic response, the sustained virologic response rate was not dose-related above 1.0 μg/kg Peginterferon Alfa-2b because of a higher relapse rate among patients treated with 1.5 μg/kg Peginterferon Alfa-2b, particularly among patients infected with genotype 1. All 3 Peginterferon Alfa-2b doses decreased liver inflammation to a greater extent than did interferon Alfa-2b, particularly in subjects with sustained responses. No new adverse events were reported, and the majority of adverse events and changes in laboratory values were mild or moderate. In conclusion, Peginterferon Alfa-2b maintained (0.5 μg/kg) or surpassed (1.0, 1.5 μg/kg) the clinical efficacy of interferon Alfa-2b while preserving its safety profile. The higher rate of virologic response during treatment with 1.5 μg/kg Peginterferon Alfa-2b in patients infected with genotype 1 and high viral levels warrants further evaluation. (H EPATOLOGY 2001;34:395-403.)

  • a randomized double blind trial comparing pegylated interferon alfa 2b to interferon alfa 2b as initial treatment for chronic hepatitis c
    2001
    Co-Authors: Karen L Lindsay, Christian Trepo, Stuart C. Gordon, John C. Hoefs, Mitchell L Shiffman, Tobias Heintges, Eugene R Schiff, Zachary Goodman, Mark Laughlin, Ruji Yao
    Abstract:

    This international, randomized, active-controlled, parallel-group, double-blind dose-finding study compared Peginterferon Alfa-2b (PegIntron) to interferon Alfa-2b for the initial treatment of compensated chronic hepatitis C. We randomly assigned 1,219 subjects to receive either the standard three-times-weekly (TIW) interferon Alfa-2b dose (3 MIU) or the once-weekly (QW) Peginterferon Alfa-2b (0.5, 1.0, or 1.5 microg/kg). Subjects were treated for 48 weeks and then followed for an additional 24 weeks. All 3 Peginterferon Alfa-2b doses significantly (P < or =.042) improved virologic response rates (loss of detectable serum HCV RNA) after treatment and after follow-up, as compared with interferon Alfa-2b. Unlike the end-of-treatment virologic response, the sustained virologic response rate was not dose-related above 1.0 microg/kg Peginterferon Alfa-2b because of a higher relapse rate among patients treated with 1.5 microg/kg Peginterferon Alfa-2b, particularly among patients infected with genotype 1. All 3 Peginterferon Alfa-2b doses decreased liver inflammation to a greater extent than did interferon Alfa-2b, particularly in subjects with sustained responses. No new adverse events were reported, and the majority of adverse events and changes in laboratory values were mild or moderate. In conclusion, Peginterferon Alfa-2b maintained (0.5 microg/kg) or surpassed (1.0, 1.5 microg/kg) the clinical efficacy of interferon Alfa-2b while preserving its safety profile. The higher rate of virologic response during treatment with 1.5 microg/kg Peginterferon Alfa-2b in patients infected with genotype 1 and high viral levels warrants further evaluation.

Mitchell L Shiffman - One of the best experts on this subject based on the ideXlab platform.

  • Enrollment and patient disposition.
    2016
    Co-Authors: Graham R. Foster, Peter Ferenci, Silke Ahlers, Mitchell L Shiffman, Carmine Coppola, Moutaz Derbala, Alessandra Orlandini, Rajender K. Reddy, Ludovico Tallarico, Georgios Bakalos
    Abstract:

    aOther reasons (more than one reason may apply to a given patient): no final confirmation from the investigator (n = 56); contraindications to therapy (n = 15); HCV RNA-negative at screening/baseline (n = 12); end-stage renal disease (n = 7); major organ transplantation (n = 2); not treated with Peginterferon alfa (n = 1) or ribavirin (n = 2); acute hepatitis C (n = 1); co-infection with HIV (n = 115); co-infection with HBV (n = 74); treatment with regimen other than Peginterferon alfa-2a/ribavirin or Peginterferon Alfa-2b/ribavirin (n = 14); treatment-naive and intended treatment duration of 72 weeks (n = 6).

  • Peginterferon alfa 2b or alfa 2a with ribavirin for treatment of hepatitis c infection
    2009
    Co-Authors: John G Mchutchison, Jonathan Mccone, Eric Lawitz, Reem Ghalib, L. Nyberg, Andrew J. Muir, Mitchell L Shiffman, Eugene R Schiff, Greg Galler, Joseph S Galati
    Abstract:

    Background 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. Methods 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 μg per kilogram of body weight per week or a low dose of 1.0 μg 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 μg 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 alfa2b regimen and the Peginterferon alfa-2a regimen. Results 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 standarddose 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 peg interferon 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 lowdose Peginterferon Alfa-2b, and 31.5% (95% CI, 27.9 to 35.2) for Peginterferon alfa2a. 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. Conclusions 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. (ClinicalTrials. gov number, NCT00081770.)

  • Antibody-Mediated Pure Red Cell Aplasia Due to Epoetin Alfa During Antiviral Therapy of Chronic Hepatitis C
    2005
    Co-Authors: R. Todd Stravitz, Harold Chung, Richard K. Sterling, Velimir A. Luketic, Arun J. Sanyal, Angie S Price, Amy Purrington, Mitchell L Shiffman
    Abstract:

    Anemia frequently complicates the treatment of chronic hepatitis C with interferon and ribavirin (RVN), requiring dose reduction and jeopardizing sustained virologic response. Increasingly, epoetin alfa is used to prevent anemia in this setting. Below, we report the first case of pure red cell aplasia (PRCA) in a patient with chronic hepatitis C who received epoetin alfa (Procrit®) to manage anti-viral treatment-induced anemia. Red blood cell transfusion-dependence developed 16 wk after the patient was started on Peginterferon Alfa-2b and RVN for chronic hepatitis C despite the simultaneous administration of epoetin alfa and subsequent discontinuation of the antiviral medications. Bone marrow biopsy was consistent with PRCA. High-titer erythropoietin antibodies, assayed by two methods, appeared shortly after epoetin alfa was administered, and were associated with a decline in serum erythropoietin to undetectable levels. Erythropoietin antibodies directed toward epoetin alfa were shown to cross react with darbepoetin alfa (Aranesp®), and a neutralization assay confirmed that they inhibited cell growth in the presence of erythropoietin. Transfusion-dependence resolved approximately 16 wk after discontinuing epoetin alfa, and 6 wk after starting danazol. PRCA caused by the development of erythropoietin antibodies is a potentially life-threatening complication of administering epoetin alfa to prevent the anemia associated with antiviral therapy in patients with chronic hepatitis C.

  • Peginterferon alfa 2b plus ribavirin compared with interferon alfa 2b plus ribavirin for initial treatment of chronic hepatitis c a randomised trial
    2001
    Co-Authors: Michael P Manns, Meihsiu Ling, Vinod K Rustgi, Stuart C. Gordon, Mitchell L Shiffman, Zachary Goodman, John G Mchutchison, Robert Reindollar, Kenneth Koury, Janice K Albrecht
    Abstract:

    Summary Background A sustained virological response (SVR) rate of 41% has been achieved with interferon Alfa-2b plus ribavirin therapy of chronic hepatitis C. In this randomised trial, Peginterferon Alfa-2b plus ribavirin was compared with interferon Alfa-2b plus ribavirin. Methods 1530 patients with chronic hepatitis C were assigned interferon Alfa-2b (3 MU subcutaneously three times per week) plus ribavirin 1000–1200 mg/day orally, Peginterferon Alfa-2b 15 μg/kg each week plus 800 mg/day ribavirin, or Peginterferon Alfa-2b 1·5 μg/kg per week for 4 weeks then 0·5 μg/kg per week plus ribavirin 1000–1200 mg/day for 48 weeks. The primary endpoint was the SVR rate (undetectable hepatitis C virus [HCV] RNA in serum at 24-week follow-up). Analyses were based on patients who received at least one dose of study medication. Findings The SVR rate was significantly higher (p=0·01 for both comparisons) in the higher-dose Peginterferon group (274/511 [54%]) than in the lower-dose Peginterferon (244/514 [47%]) or interferon (235/505 [47%]) groups. Among patients with HCV genotype 1 infection, the corresponding SVR rates were 42% (145/348), 34% (118/349), and 33% (114/343). The rate for patients with genotype 2 and 3 infections was about 80% for all treatment groups. Secondary analyses identified bodyweight as an important predictor of SVR, prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight (mg/kg). Side-effect profiles were similar between the treatment groups. Interpretation In patients with chronic hepatitis C, the most effective therapy is the combination of Peginterferon Alfa-2b 1·5 μg/kg per week plus ribavirin. The benefit is mostly achieved in patients with HCV genotype 1 infections.

  • a randomized double blind trial comparing pegylated interferon alfa 2b to interferon alfa 2b as initial treatment for chronic hepatitis c
    2001
    Co-Authors: Karen L Lindsay, Mark A. Laughlin, Christian Trepo, Stuart C. Gordon, John C. Hoefs, Mitchell L Shiffman, Tobias Heintges, Eugene R Schiff, Zachary Goodman, Janice K Albrecht
    Abstract:

    Abstract This international, randomized, active-controlled, parallel-group, double-blind dose-finding study compared Peginterferon Alfa-2b (PegIntron™) to interferon Alfa-2b for the initial treatment of compensated chronic hepatitis C. We randomly assigned 1,219 subjects to receive either the standard three-times-weekly (TIW) interferon Alfa-2b dose (3 MIU) or the once-weekly (QW) Peginterferon Alfa-2b (0.5, 1.0, or 1.5 μg/kg). Subjects were treated for 48 weeks and then followed for an additional 24 weeks. All 3 Peginterferon Alfa-2b doses significantly ( P ≤ .042) improved virologic response rates (loss of detectable serum HCV RNA) after treatment and after follow-up, as compared with interferon Alfa-2b. Unlike the end-of-treatment virologic response, the sustained virologic response rate was not dose-related above 1.0 μg/kg Peginterferon Alfa-2b because of a higher relapse rate among patients treated with 1.5 μg/kg Peginterferon Alfa-2b, particularly among patients infected with genotype 1. All 3 Peginterferon Alfa-2b doses decreased liver inflammation to a greater extent than did interferon Alfa-2b, particularly in subjects with sustained responses. No new adverse events were reported, and the majority of adverse events and changes in laboratory values were mild or moderate. In conclusion, Peginterferon Alfa-2b maintained (0.5 μg/kg) or surpassed (1.0, 1.5 μg/kg) the clinical efficacy of interferon Alfa-2b while preserving its safety profile. The higher rate of virologic response during treatment with 1.5 μg/kg Peginterferon Alfa-2b in patients infected with genotype 1 and high viral levels warrants further evaluation. (H EPATOLOGY 2001;34:395-403.)

Stuart C. Gordon - One of the best experts on this subject based on the ideXlab platform.

  • efficacy of boceprevir an ns3 protease inhibitor in combination with Peginterferon alfa 2b and ribavirin in treatment naive patients with genotype 1 hepatitis c infection sprint 1 an open label randomised multicentre phase 2 trial
    2010
    Co-Authors: Eric Lawitz, Jonathan Mccone, Joseph S Galati, David Pound, John M. Vierling, Natarajan Ravendhran, Stuart C. Gordon, M. Davis, Lorenzo Rossaro
    Abstract:

    Findings Patients in all four boceprevir groups had higher rates of SVR than did the control group (58/107 [54%, 95% CI 44–64], p=0·013 for PRB28; 58/103 [56%, 44–66], p=0·005 for PR4/PRB24; 69/103 [67%, 57–76], p<0·0001 for PRB48; and 77/103 [75%, 65–83], p<0·0001 for PR4/PRB44; vs 39/104 [38%, 28–48] for PR48 control). Lowdose ribavirin was associated with a high rate of viral breakthrough (16/59 [27%]), and a rate of relapse (six of 27 [22%]) similar to control (12/51 [24%]). Boceprevir-based groups had higher rates of anaemia (227/416 [55%] vs 35/104 [34%]) and dysgeusia (111/416 [27%] vs nine of 104 [9%]) than did the control group.

  • Peginterferon alfa 2b plus ribavirin compared with interferon alfa 2b plus ribavirin for initial treatment of chronic hepatitis c a randomised trial
    2001
    Co-Authors: Michael P Manns, Meihsiu Ling, Vinod K Rustgi, Stuart C. Gordon, Mitchell L Shiffman, Zachary Goodman, John G Mchutchison, Robert Reindollar, Kenneth Koury, Janice K Albrecht
    Abstract:

    Summary Background A sustained virological response (SVR) rate of 41% has been achieved with interferon Alfa-2b plus ribavirin therapy of chronic hepatitis C. In this randomised trial, Peginterferon Alfa-2b plus ribavirin was compared with interferon Alfa-2b plus ribavirin. Methods 1530 patients with chronic hepatitis C were assigned interferon Alfa-2b (3 MU subcutaneously three times per week) plus ribavirin 1000–1200 mg/day orally, Peginterferon Alfa-2b 15 μg/kg each week plus 800 mg/day ribavirin, or Peginterferon Alfa-2b 1·5 μg/kg per week for 4 weeks then 0·5 μg/kg per week plus ribavirin 1000–1200 mg/day for 48 weeks. The primary endpoint was the SVR rate (undetectable hepatitis C virus [HCV] RNA in serum at 24-week follow-up). Analyses were based on patients who received at least one dose of study medication. Findings The SVR rate was significantly higher (p=0·01 for both comparisons) in the higher-dose Peginterferon group (274/511 [54%]) than in the lower-dose Peginterferon (244/514 [47%]) or interferon (235/505 [47%]) groups. Among patients with HCV genotype 1 infection, the corresponding SVR rates were 42% (145/348), 34% (118/349), and 33% (114/343). The rate for patients with genotype 2 and 3 infections was about 80% for all treatment groups. Secondary analyses identified bodyweight as an important predictor of SVR, prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight (mg/kg). Side-effect profiles were similar between the treatment groups. Interpretation In patients with chronic hepatitis C, the most effective therapy is the combination of Peginterferon Alfa-2b 1·5 μg/kg per week plus ribavirin. The benefit is mostly achieved in patients with HCV genotype 1 infections.

  • a randomized double blind trial comparing pegylated interferon alfa 2b to interferon alfa 2b as initial treatment for chronic hepatitis c
    2001
    Co-Authors: Karen L Lindsay, Mark A. Laughlin, Christian Trepo, Stuart C. Gordon, John C. Hoefs, Mitchell L Shiffman, Tobias Heintges, Eugene R Schiff, Zachary Goodman, Janice K Albrecht
    Abstract:

    Abstract This international, randomized, active-controlled, parallel-group, double-blind dose-finding study compared Peginterferon Alfa-2b (PegIntron™) to interferon Alfa-2b for the initial treatment of compensated chronic hepatitis C. We randomly assigned 1,219 subjects to receive either the standard three-times-weekly (TIW) interferon Alfa-2b dose (3 MIU) or the once-weekly (QW) Peginterferon Alfa-2b (0.5, 1.0, or 1.5 μg/kg). Subjects were treated for 48 weeks and then followed for an additional 24 weeks. All 3 Peginterferon Alfa-2b doses significantly ( P ≤ .042) improved virologic response rates (loss of detectable serum HCV RNA) after treatment and after follow-up, as compared with interferon Alfa-2b. Unlike the end-of-treatment virologic response, the sustained virologic response rate was not dose-related above 1.0 μg/kg Peginterferon Alfa-2b because of a higher relapse rate among patients treated with 1.5 μg/kg Peginterferon Alfa-2b, particularly among patients infected with genotype 1. All 3 Peginterferon Alfa-2b doses decreased liver inflammation to a greater extent than did interferon Alfa-2b, particularly in subjects with sustained responses. No new adverse events were reported, and the majority of adverse events and changes in laboratory values were mild or moderate. In conclusion, Peginterferon Alfa-2b maintained (0.5 μg/kg) or surpassed (1.0, 1.5 μg/kg) the clinical efficacy of interferon Alfa-2b while preserving its safety profile. The higher rate of virologic response during treatment with 1.5 μg/kg Peginterferon Alfa-2b in patients infected with genotype 1 and high viral levels warrants further evaluation. (H EPATOLOGY 2001;34:395-403.)

  • a randomized double blind trial comparing pegylated interferon alfa 2b to interferon alfa 2b as initial treatment for chronic hepatitis c
    2001
    Co-Authors: Karen L Lindsay, Christian Trepo, Stuart C. Gordon, John C. Hoefs, Mitchell L Shiffman, Tobias Heintges, Eugene R Schiff, Zachary Goodman, Mark Laughlin, Ruji Yao
    Abstract:

    This international, randomized, active-controlled, parallel-group, double-blind dose-finding study compared Peginterferon Alfa-2b (PegIntron) to interferon Alfa-2b for the initial treatment of compensated chronic hepatitis C. We randomly assigned 1,219 subjects to receive either the standard three-times-weekly (TIW) interferon Alfa-2b dose (3 MIU) or the once-weekly (QW) Peginterferon Alfa-2b (0.5, 1.0, or 1.5 microg/kg). Subjects were treated for 48 weeks and then followed for an additional 24 weeks. All 3 Peginterferon Alfa-2b doses significantly (P < or =.042) improved virologic response rates (loss of detectable serum HCV RNA) after treatment and after follow-up, as compared with interferon Alfa-2b. Unlike the end-of-treatment virologic response, the sustained virologic response rate was not dose-related above 1.0 microg/kg Peginterferon Alfa-2b because of a higher relapse rate among patients treated with 1.5 microg/kg Peginterferon Alfa-2b, particularly among patients infected with genotype 1. All 3 Peginterferon Alfa-2b doses decreased liver inflammation to a greater extent than did interferon Alfa-2b, particularly in subjects with sustained responses. No new adverse events were reported, and the majority of adverse events and changes in laboratory values were mild or moderate. In conclusion, Peginterferon Alfa-2b maintained (0.5 microg/kg) or surpassed (1.0, 1.5 microg/kg) the clinical efficacy of interferon Alfa-2b while preserving its safety profile. The higher rate of virologic response during treatment with 1.5 microg/kg Peginterferon Alfa-2b in patients infected with genotype 1 and high viral levels warrants further evaluation.

Larrousse Morellón Maria - One of the best experts on this subject based on the ideXlab platform.

  • Avances en el diagnóstico de la fibrosis hepática, manejo y tratamiento de la hepatitis crónica por el virus de la hepatitis C en pacientes infectados por el virus de la inmunodeficiencia humana
    2009
    Co-Authors: Larrousse Morellón Maria
    Abstract:

    DE LA TESIS:En los países desarrollados, la introducción del tratamiento antirretroviral de gran actividad (TARGA) ha revolucionado la perspectiva del paciente infectado por el virus de la Inmunodeficiencia Humana tipo 1(VIH), produciendo un aumento espectacular de la supervivencia y una reducción muy importante de las infecciones oportunistas y neoplasias asociadas al síndrome de inmunodeficiencia adquirida (SIDA). En este contexto, la infección crónica por el virus de la hepatitis C (VHC) ha tomado gran relevancia clínica situándose como una de las primeras causas de ingreso hospitalario y muerte en los pacientes infectados por el VIH.La coinfección de estos virus no es un proceso aislado. De los 40 millones estimados de pacientes infectados por el VIH-1 en el mundo, aproximadamente un tercio presenta una infección crónica por el VHC lo que supone unos 12 millones de pacientes coinfectados a nivel mundial. Aproximadamente el 30% de la población seropositiva está coinfectada por el VHC. Esta elevada tasa de prevalencia de coinfección se debe en gran medida a que ambos virus comparten similares vías de transmisión. Si nos centramos exclusivamente en los pacientes que han adquirido la infección por el VIH por vía parenteral, principalmente en pacientes adictos a drogas endovenosas o pacientes hemofílicos, este número se eleva aproximadamente a un 90% de los pacientes (6). Estudios epidemiológicos han demostrado que el 65% de los pacientes con adicción a drogas por vía parenteral presentan anticuerpos para el VHC a los 12 meses tras el inicio del consumo. Este dato permite calcular el tiempo que un paciente lleva infectado por el VHC. En los últimos años se ha detectado que los pacientes coinfectados por ambos virus tienen peor pronóstico que los monoinfectados por VHC. La progresión de la enfermedad hepática se encuentra acelerada, los pacientes presentan una mayor progresión a cirrosis, mayor incidencia de hepatocarcinoma, y menor supervivencia desde la primera descompensación respecto a los pacientes con monoinfectados por el VHC. Por tanto, la consideración del tratamiento de la VHC es una prioridad en el manejo y tratamiento de los pacientes coinfectados por el VIH y VHC.La presente tesis recoge un total de cinco artículos en los que se ha difundido la investigación asociada con la misma. El primero ("Noninvasive Diagnosis of Hepatic Fibrosis in HIV/HCV-Coinfected Patients". JAIDS 2007; 46:304-311) analiza los marcadores no invasivos de fibrosis hepática en pacientes infectados por el VIH y VHC. El segundo ("Peginterferon Alfa-2b plus ribavirin compared with interferon Alfa-2b plus ribavirin for treatment of HIV/HCV co-infected patients". AIDS. 2004; 18(13):27-36.) contiene un estudio clínico que compara dos estrategias de tratamiento de la hepatopatía por VHC con Peginterferon Alfa-2b con ribavirina comparada con interferon Alfa-2b con ribavirina en pacientes coinfectados por el VIH y el VHC. El tercer artículo ("Predictive Value of Early Virologic Response in HIV/Hepatitis C Virus-Coinfected Patients Treated With an Interferon-Based Regimen Plus Ribavirin". JAIDS 2007; 44:174-178.) estudia el valor predictivo de la RVP en pacientes coinfectados por VIH y VHC tratados con un régimen basado un interferon y ribavirina. Por su parte, el artículo número cuatro ("Randomized trial comparing pegylated interferon alpha-2b versus pegylated interferon alpha-2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients". Hepatology 2009; 49:22-31) realiza un estudio clínico randomizado que compara dos estrategias de tratamiento con interferón pegilado alfa 2a versus interferon pegilado alfa 2b junto con Ribavirina en ambos grupos en pacientes coinfectados por el VIH y VHC. Por último, el artículo cinco ("Pharmacokinetics of Fosamprenavir plus Ritonavir in HIV-1-infected Adult Subjects with Hepatic Impairment." Antimicrob. Agents Chemother. 2009; 53: 5185-96) realiza un estudio de farmacocinética de fase I con fosamprenavir y ritonavir en pacientes infectados por el VIH con disfunción hepática

  • Avances en el diagnóstico de la fibrosis hepática, manejo y tratamiento de la hepatitis crónica por el virus de la hepatitis C en pacientes infectados por el virus de la inmunodeficiencia humana
    2009
    Co-Authors: Larrousse Morellón Maria
    Abstract:

    [spa] En los países desarrollados, la introducción del tratamiento antirretroviral de gran actividad (TARGA) ha revolucionado la perspectiva del paciente infectado por el virus de la Inmunodeficiencia Humana tipo 1(VIH), produciendo un aumento espectacular de la supervivencia y una reducción muy importante de las infecciones oportunistas y neoplasias asociadas al síndrome de inmunodeficiencia adquirida (SIDA). En este contexto, la infección crónica por el virus de la hepatitis C (VHC) ha tomado gran relevancia clínica situándose como una de las primeras causas de ingreso hospitalario y muerte en los pacientes infectados por el VIH.La coinfección de estos virus no es un proceso aislado. De los 40 millones estimados de pacientes infectados por el VIH-1 en el mundo, aproximadamente un tercio presenta una infección crónica por el VHC lo que supone unos 12 millones de pacientes coinfectados a nivel mundial. Aproximadamente el 30% de la población seropositiva está coinfectada por el VHC. Esta elevada tasa de prevalencia de coinfección se debe en gran medida a que ambos virus comparten similares vías de transmisión. Si nos centramos exclusivamente en los pacientes que han adquirido la infección por el VIH por vía parenteral, principalmente en pacientes adictos a drogas endovenosas o pacientes hemofílicos, este número se eleva aproximadamente a un 90% de los pacientes (6). Estudios epidemiológicos han demostrado que el 65% de los pacientes con adicción a drogas por vía parenteral presentan anticuerpos para el VHC a los 12 meses tras el inicio del consumo. Este dato permite calcular el tiempo que un paciente lleva infectado por el VHC. En los últimos años se ha detectado que los pacientes coinfectados por ambos virus tienen peor pronóstico que los monoinfectados por VHC. La progresión de la enfermedad hepática se encuentra acelerada, los pacientes presentan una mayor progresión a cirrosis, mayor incidencia de hepatocarcinoma, y menor supervivencia desde la primera descompensación respecto a los pacientes con monoinfectados por el VHC. Por tanto, la consideración del tratamiento de la VHC es una prioridad en el manejo y tratamiento de los pacientes coinfectados por el VIH y VHC.La presente tesis recoge un total de cinco artículos en los que se ha difundido la investigación asociada con la misma. El primero ("Noninvasive Diagnosis of Hepatic Fibrosis in HIV/HCV-Coinfected Patients". JAIDS 2007; 46:304-311) analiza los marcadores no invasivos de fibrosis hepática en pacientes infectados por el VIH y VHC. El segundo ("Peginterferon Alfa-2b plus ribavirin compared with interferon Alfa-2b plus ribavirin for treatment of HIV/HCV co-infected patients". AIDS. 2004; 18(13):27-36.) contiene un estudio clínico que compara dos estrategias de tratamiento de la hepatopatía por VHC con Peginterferon Alfa-2b con ribavirina comparada con interferon Alfa-2b con ribavirina en pacientes coinfectados por el VIH y el VHC. El tercer artículo ("Predictive Value of Early Virologic Response in HIV/Hepatitis C Virus-Coinfected Patients Treated With an Interferon-Based Regimen Plus Ribavirin". JAIDS 2007; 44:174-178.) estudia el valor predictivo de la RVP en pacientes coinfectados por VIH y VHC tratados con un régimen basado un interferon y ribavirina. Por su parte, el artículo número cuatro ("Randomized trial comparing pegylated interferon alpha-2b versus pegylated interferon alpha-2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients". Hepatology 2009; 49:22-31) realiza un estudio clínico randomizado que compara dos estrategias de tratamiento con interferón pegilado alfa 2a versus interferon pegilado alfa 2b junto con Ribavirina en ambos grupos en pacientes coinfectados por el VIH y VHC. Por último, el artículo cinco ("Pharmacokinetics of Fosamprenavir plus Ritonavir in HIV-1-infected Adult Subjects with Hepatic Impairment." Antimicrob. Agents Chemother. 2009; 53: 5185-96) realiza un estudio de farmacocinética de fase I con fosamprenavir y ritonavir en pacientes infectados por el VIH con disfunción hepática