Re-treatment with interferon alfa of patients with chronic hepatitis C

Chow, Wan-Cheng; Boyer, Nathalie; Pouteau, M.; Castelnau, Corinne; Martinot‐Peignoux, Michèle; Martins-Amado, Veronique; Degos, Françoise; Maghinici, Crina; Sinègre, M.; Benhamou, Jean‐Pierre; Degott, Claude; Erlinger, S; Marcellin, Patrick

doi:10.1002/hep.510270432

Cited by 28 publications

(18 citation statements)

References 23 publications

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“…These included age, higher ALT levels, lower ␥-glutamyltransferase levels, negative HCV RNA at the end of the first cycle, low levels of HCV RNA before retreatment, and increased IFN dose in the second course. 2,4,[6][7][8][9]14 Finally, Chow et al 3 failed to identify any predictive item significantly associated with an SR. The drawing of firm conclusions based on the results of these studies is hampered by the small sample size and by the imbalance between the high number of variables included in multivariate models and the small number of events observed, potentially leading to false-negative or false-positive results.…”

Section: Discussionmentioning

confidence: 99%

“…The study database consists of 549 consecutive relapsers included in randomized trials or prospective cohort studies, who had received in the first course a total IFN dose of at least 234 megaunits (MU) (e.g., 3 MU three times weekly for 6 months), who were retreated within 24 months after the end of the first course and who had the following criteria for inclusion before the initial treatment: age over 18 years; alanine transaminase (ALT) level higher than 1.5 times the upper normal limit for at least 6 months before entry; anti-HCV positivity before entry; histological features of chronic hepatitis (without or with cirrhosis); serum hepatitis B surface antigen negative; antinuclear, antiactin muscle and antimitochondrial antibodies negative; and human immunodeficiency virus antibody negative. Two hundred forty-nine patients (45.4%) came from published randomized clinical trials or cohort studies, 3,4,6,7,9,10 whereas the remaining 300 patients (54.6%) represent original unpublished data from each center' s files.…”

Section: Methodsmentioning

confidence: 99%

“…On the basis of experience gathered from the treatment of naive patients 25 and from preliminary evidence on retreated patients 3,5 we selected, as candidate predictors of biochemical and virological SR, age, sex, known disease duration (defined as months elapsed since first finding of abnormal liver tests), ALT levels, platelets, ␥-glutamyl transferase, baseline liver histology, HCV genotypes, HCV-RNA status at the end of the first cycle, HCV-RNA levels before retreatment, and the amount of IFN received during the first and the second cycle. Variables significant on univariate analysis (P Ͻ .05) were included in a multivariate logistic regression model.…”

Section: Methodsmentioning

confidence: 99%

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Chronic hepatitis C: Interferon retreatment of relapsers. A meta-analysis of individual patient data

et al. 1999

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Relapse after interferon (IFN) therapy for chronic hepatitis C virus (HCV) infection occurs in 50% of patients after the initial response. The benefit of retreatment with IFN alone has not been assessed in large controlled studies. To assess the effectiveness and the tolerability of IFN retreatment and to identify the optimal second course regimen, we performed a meta-analysis of individual patient's data on a set of 549 patients (mean age 43.8 years; 12.2 SD, men: 65%) who had an end-of-treatment biochemical response to a first IFN course and then relapsed. Retreatment was started within 24 months after the end of the first course. In chronic hepatitis C, the goal of treatment, defined as complete sustained response (SR) (normal alanine transaminase levels and undetectable serum hepatitis C virus-RNA (HCV-RNA) levels 6 to 12 months after therapy) is achieved in less than 20% of patients with standard interferon (IFN)-alfa schedule. 1 Although a complete end-of-treatment response (ETR) is obtained in about 50% of patients, half of them will relapse with a reappearance of viremia and liver necroinflammation soon after stopping therapy. Therefore, relapse remains a major issue in the long-term management of the disease. Several studies of retreatment with IFN alone in patients who had an ETR but subsequently relapsed after stopping IFN have been published. The results of these studies are inconclusive or conflicting because of the relatively small samples and the difficulty of generalizing patients owing to the differences in patient characteristics, study design, regimens, and types of IFN administered. Although the conclusions of the National Institutes of Health Consensus Development Conference for the retreatment of relapse of chronic hepatitis C have recently been published, 22 important questions still remain unanswered. Is monotherapy retreatment useful in relapsers? Are there any differences in the effectiveness of IFN retreatment between cirrhotic and noncirrhotic patients, between different HCV genotypes and, finally, between different second course regimens?To increase the statistical power and to resolve uncertainty we propose a meta-analysis of the individual patient' s data (MIPD), drawing from 1 Japanese center and 15 European centers. The aims of this MIPD were (1) to assess the efficacy and tolerability of IFN retreatment in obtaining a complete SR in relapsers; (2) to evaluate which retreatment schedule should be used and, finally, (3) to identify possible predictors of complete SR. Our aims seem particularly important at a time when combination therapy (IFN plus ribavirin) is being confirmed as an effective treatment for relapsers. MATERIALS AND METHODSThe study was planned within the European Concerted Action on Viral Hepatitis (EUROHEP). Twenty-four centers throughout the world, all with reported experience in this field, were invited to participate: 15 centers in Europe and 1 center in Japan agreed to make data available. Individual patient data from previously published and unpublished stud...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Chronic hepatitis C: Interferon retreatment of relapsers. A meta-analysis of individual patient data

et al. 1999

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“…Because all patients enrolled in the present study were previous IFN-α non-responders, a retreatment arm with IFN-α monotherapy as a control group was refused for ethical reasons [34, 35, 36, 37]. Informed written consent was obtained from all patients.…”

Section: Methodsmentioning

confidence: 99%

Retreatment with Interferon-Alpha and Ribavirin in Primary Interferon-Alpha Non-Responders with Chronic Hepatitis C

Teuber

Berg²,

Hoffmann³

et al. 2000

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Background/Aims: Combination therapy with interferon-α (IFN-α) plus ribavirin is more efficacious than IFN-α monotherapy in previously untreated patients with chronic hepatitis C and patients with IFN-α relapse. Only limited data are available in IFN-α non-responders. In a multicenter trial we therefore evaluated the efficacy of combination therapy in IFN-α-resistant chronic hepatitis C. Methods: Eighty-two patients (mean age 46.8 years, 54 males, 28 females) with chronic hepatitis C were treated with IFN-α-2a (3 × 6 MIU/week) and ribavirin (14 mg/kg daily) for 12 weeks. Thereafter, treatment was continued only in virological responders (undetectable serum HCV RNA at week 12) with an IFN-α dose of 3 × 3 MIU/week and without ribavirin for a further 9 months. The primary study endpoint was an undetectable HCV RNA by RT-PCR at the end of the 24-week follow-up period. Results: After 12 weeks of combination therapy, an initial virological response was observed in 29 of 82 (35.4%) patients. Due to a high breakthrough rate after IFN-α dose reduction and ribavirin discontinuation, an end-of-treatment response was only achieved in 12 of 82 (14.6%) patients. After the follow-up period, a sustained virological response was observed in 8 of 82 (9.8%) patients. Infection with HCV genotype 3 was the only pretreatment parameter, which could predict a sustained response (HCV-1, 5%; HCV-3, 57.1%; p < 0.001). Conclusions: Despite a high initial response rate of 35.4%, sustained viral clearance was achieved only in 9.8% of the retreated primary IFN-α non-responders. Higher IFN-α induction and maintenance dose, as well as prolonged ribavirin treatment may possibly increase the virological response rates in non-responders, particularly in those infected by HCV-1.

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“…However, the optimal retreatment regimen is not established. [8][9][10][11][12][13][14][15][16] We compared the efficacy of three IFN-␣2b regimens in patients with CHC who showed a complete response followed by a relapse after an initial 6-month treatment.…”

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Better Efficacy of A 12–Month Interferon Alfa–2B Retreatment in Patients With Chronic Hepatitis C Relapsing After A 6–Month Treatment: A Multicenter, Controlled, Randomized Trial

Payen

Izopet²,

Galindo-Migeot

et al. 1998

Hepatology

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We studied the efficacy of three interferon alfa-2b (IFN␣2b) regimens for the retreatment of patients with chronic hepatitis C (CHC) with prior complete response followed by relapse. Consecutive patients with CHC who had a complete biochemical response but relapse after a first course of 6 months of IFN with 3 million units (MU) given subcutaneously three times per week were enrolled in the study. Six to 24 months after the end of the first treatment, the patients were randomly assigned to receive IFN with either the same regimen (group 1), a regimen of 12 months with 3 MU (group 2), or a regimen of 6 months with 10 MU (group 3). Sustained biochemical response was defined as normal serum alanine transaminase (ALT) values during the follow-up and sustained virological response as a clearance of hepatitis C virus (HCV) RNA from the serum at the end of follow-up (6 months' posttreatment). Histological improvement was defined as a decrease of 1 point in Metavir score between the first liver biopsy and a biopsy performed at 6 months' postretreatment. Two hundred forty-seven patients were randomized: 75 to group 1, 91 to group 2, and 81 to group 3. In an intent-to-treat analysis, 12%, 36.3%, and 18.5% of patients had a sustained biochemical response after retreatment in groups 1, 2, and 3, respectively (P F .001); 13.8%, 32.4%, and 17.2% of patients had a sustained virological response after retreatment in groups 1, 2, and 3, respectively (P F .05). A low viral load and patients in group 2 were independently associated with a sustained biochemical response. A low Knodell score index before treatment, patients with a high level of ALT before retreatment, genotype 3, low viral load, and patients in group 2 were independently associated with sustained virological response. Younger age, a high level of ALT, a low level of ␥-glutamyl transferase before retreatment, low viral load, and patients in group 2 were independently associated with sustained biochemical and virological response. Among the 80 patients with repeated liver biopsies, 47.6% had improved histological activity scores; this improvement was associated with a sustained biochemical and virological response. In patients with CHC initially treated with 3 MU of IFN given subcutaneously three times per week over a 6-month period, and who subsequently developed a relapse after a biochemical response, retreatment with a regimen of 3 MU of IFN given three times per week for 12 months produced better biochemical and virological sustained response rates than regimens involving a higher dose or a shorter duration of retreatment. The biochemical and virological sustained response was associated with histological improvement. (HEPATOLOGY 1998;28: 1680-1686.)

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Re-treatment with interferon alfa of patients with chronic hepatitis C

Cited by 28 publications

References 23 publications

Chronic hepatitis C: Interferon retreatment of relapsers. A meta-analysis of individual patient data

Chronic hepatitis C: Interferon retreatment of relapsers. A meta-analysis of individual patient data

Retreatment with Interferon-Alpha and Ribavirin in Primary Interferon-Alpha Non-Responders with Chronic Hepatitis C

Better Efficacy of A 12–Month Interferon Alfa–2B Retreatment in Patients With Chronic Hepatitis C Relapsing After A 6–Month Treatment: A Multicenter, Controlled, Randomized Trial

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