Interferon Alfa-2b Alone or in Combination with Ribavirin for the Treatment of Relapse of Chronic Hepatitis C

Davis, Gary L.; Esteban, Rafael; Rustgi, Vinod K.; Hoefs, John C.; Gordon, Stuart C.; Trépo, Christian; Shiffman, Mitchell L.; Zeuzem, Stefan; Craxı̀, Antonio; Ling, Mei-Hsiu; Albrecht, Janice K.

doi:10.1056/nejm199811193392102

Cited by 1,188 publications

(846 citation statements)

References 42 publications

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“…However, the patient adamantly maintained that he was using the drug as directed. The anomalous resistance of this subject's erythrocytes to the usual deleterious effect of RBV has been observed in previous reports that found that the occasional patient receiving RBV does not experience a fall in hemoglobin [1][2][3]. The physiology underlying this resistance remains speculative.…”

Section: Discussionmentioning

confidence: 70%

“…The complexity, radioactive exposure, and time commitment of this technique markedly reduces its clinical utility. As a result, available evidence that the anemia of RBVtreated subjects results from rapid turnover of RBCs consists solely of the demonstration of increased reticulocyte counts in some subjects [1][2][3]6,7].…”

Section: Discussionmentioning

confidence: 99%

“…While this activity is not deleterious to most human cells, erythrocytes (RBCs) are adversely affected [2][3][4], and the vast majority of subjects receiving RBV become anemic [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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Use of alveolar carbon monoxide to measure the effect of ribavirin on red blood cell survival†

Virtue

Furne

et al. 2004

American J Hematol

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A major side effect of ribavirin (RBV) treatment is anemia. While this anemia is thought to result from increased RBC turnover, RBC survival has not been determined in subjects receiving RBV due to the complexity of the techniques commonly used to quantitate RBC life span. We recently described a simple, rapid, non-invasive technique that utilizes measurements of alveolar carbon monoxide (CO) concentration to determine RBC survival. In the present report, this method was employed to assess RBC survival in patients receiving RBV for hepatitis C. Each of the 31 measurements of RBC survival in 12 subjects with RBV-associated anemia was below the lower limit of normal (77 days), and the average survival (46 ± 14 days) in these subjects was only about 38% of that of healthy controls (122 ± 23 days). Five hepatitis C patients not undergoing RBV treatment had normal RBC survivals (112 ± 17 days). While the mean reticulocyte percentage was significantly elevated in subjects treated with RBV, 59% of these measurements fell within the limits of normal. We conclude that RBV-associated anemia consistently is associated with reduced RBC survival as determined from breath CO measurements and that this reduced survival frequently is not associated with an elevated reticulocyte count. Am.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

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Use of alveolar carbon monoxide to measure the effect of ribavirin on red blood cell survival†

Virtue

Furne

et al. 2004

American J Hematol

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“…Ribavirin is a mutagen and inhibitor of viral RNA polymerase. 13,14 It shows antiviral activity against a variety of RNA viruses and is used to treat infections of hepatitis C virus in combination with interferon-a 15,16 and of lassa fever virus. 17 The method of using antiviral drugs might offer a novel approach for regulated SeV-mediated gene expression in primate ES cells.…”

Section: Introductionmentioning

confidence: 99%

Efficient and stable Sendai virus-mediated gene transfer into primate embryonic stem cells with pluripotency preserved

et al. 2004

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Efficient gene transfer and regulated transgene expression in primate embryonic stem (ES) cells are highly desirable for future applications of the cells. In the present study, we have examined using the nonintegrating Sendai virus (SeV) vector to introduce the green fluorescent protein (GFP) gene into non-human primate cynomolgus ES cells. The GFP gene was vigorously and stably expressed in the cynomolgus ES cells for a year. The cells were able to form fluorescent teratomas when transplanted into immunodeficient mice. They were also able to differentiate into fluorescent embryoid bodies, neurons, and mature blood cells. In addition, the GFP expression levels were reduced dose-dependently by the addition of an anti-RNA virus drug, ribavirin, to the culture. Thus, SeV vector will be a useful tool for efficient gene transfer into primate ES cells and the method of using antiviral drugs should allow further investigation for regulated SeV-mediated gene expression.

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“…9,10 The combination of ribavirin with IFN also has been shown to be effective for relapsers and nonresponders to standard IFN therapy. Efficacy has been reported to range from 29% to 49% in relapsers 12,13 and from 9.8% to 40% in nonresponders to IFN [14][15][16] ; however, in most of these studies, IFN treatment was carried out at doses of 3 million units (MU) 3 times per week. This dose is lower than that currently used in most European countries for IFN monotherapy (5 MU 3 times per week).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Tolerability of Combination Therapy with Interferon-Alfa Plus Ribavirin in Patients with Chronic Hepatitis C Virus Infection: A Single-Center Study in Relapsers and Nonresponders to Previous Treatment with High-Dose Interferon-Alfa Monotherapy

Benini

Distefano

Baisini

et al. 2003

Current Therapeutic Research

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Background: In chronic hepatitis C virus (HCV) infection, interferon (IFN) monotherapy usually is carried out at doses of 3 to 6 million units (MU) 3 times per week, but treatment efficacy is low.Objective: The aim of our study was to assess the efficacy and tolerability of IFN-alfa 2b in combination with ribavirin in relapsers and nonresponders to high-dose IFN treatment (5 to 6 MU 3 times per week). We measured the biochemical and virologic responses to treatment and the risk for relapse during the 24 weeks following the end of treatment.Methods: Patients with chronic HCV infection (relapsers and nonresponders to a previous treatment with high-dose IFN) received IFN-alfa 2b , 3 MU 3 times per week, and ribavirin, 1000 or 1200 mg/d for 24 or 48 weeks. The patients were then followed up for an additional 24 weeks. Sustained response was defined as normal serum alanine aminotransferase (ALT) level and undetectable HCV RNA 24 weeks after treatment was stopped.Results: Forty-three patients (32 men, 11 women; mean [SD] age, 45 [2] years; 10 relapsers, 33 nonresponders) were included in the study. Four patients were withdrawn from the study at week 4 of treatment because of treatment-related adverse events, and 1 dropped out. At the end of the treatment period, normalization of serum ALT levels and undetectable HCV RNA levels were seen in 58.1% and 30.2% of patients, respectively. No significant difference in virologic response at the end of treatment was found between nonresponders (10/33 [30.3%]) to previous IFN therapy and relapsers (3/10 [30.0%]). At the end of follow-up, 3 (7.0%) treated patients had sustained response (2 nonresponders to the first IFN course and 1 relapser). All of the patients with sustained response were treated for 24 weeks.Accepted for publication December 20, 2002. doi:10.1016/S0011-393X(03)00024-9 Reproduction in whole or part is not permitted.0011-393X/03/$19.00 140Copyright ą 2003 Excerpta Medica, Inc. F. Benini et al. Conclusion:Based on the results of our study, combination therapy with IFN-alfa and ribavirin may be of value in a limited number of patients with chronic HCV infection who do not respond to, or relapse after, a first course of treatment with high-dose IFN monotherapy. (Curr Ther Res Clin Exp. 2003;64:140-150) Copyright Ć 2003 Excerpta Medica, Inc.Key words: chronic hepatitis C virus, high-dose interferon, ribavirin, combination therapy. INTRODUCTIONChronic infection with hepatitis C virus (HCV) is estimated to affect Ͼ5 million people in Europe, almost 4 million in the United States, and 170 million individuals worldwide. 1,2 In ∼15% to 20% of these individuals, infection progresses to chronic hepatitis and cirrhosis. 3,4 Interferon (IFN)-alfa monotherapy has been, for a decade, the only effective treatment for chronic HCV infection, 5-7 but treatment efficacy is low. Sustained response, defined as viral clearance persisting for Ͼ24 weeks after treatment is stopped, occurs in only 30% of treated patients, whereas 15% to 25% of patients relapse during the 24...

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Interferon Alfa-2b Alone or in Combination with Ribavirin for the Treatment of Relapse of Chronic Hepatitis C

Abstract: In patients with chronic hepatitis C who relapse after treatment with interferon, therapy with interferon and oral ribavirin results in higher rates of sustained virologic, biochemical, and histologic response than treatment with interferon alone.

Cited by 1,188 publications

References 42 publications

Use of alveolar carbon monoxide to measure the effect of ribavirin on red blood cell survival†

Use of alveolar carbon monoxide to measure the effect of ribavirin on red blood cell survival†

Efficient and stable Sendai virus-mediated gene transfer into primate embryonic stem cells with pluripotency preserved

Efficacy and Tolerability of Combination Therapy with Interferon-Alfa Plus Ribavirin in Patients with Chronic Hepatitis C Virus Infection: A Single-Center Study in Relapsers and Nonresponders to Previous Treatment with High-Dose Interferon-Alfa Monotherapy

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