Comparison of 1 or 3 MU of interferon alfa-2b and placebo in patients with chronic non-A, non-B hepatitis

Causse, Xavier; Godinot, Hubert; Chevallier, M.; Chossegros, P.; Zoulim, Fabien; Ouzan, Denis; Heyraud, Jean-Paul; Fontanges, Thierry; Albrecht, Janice K.; Meschievitz, Carlton; Trépo, Christian

doi:10.1016/0016-5085(91)90030-o

Cited by 243 publications

(98 citation statements)

References 15 publications

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“…Diagnosis was units (MU) thrice weekly for 6 months. [1][2][3][4][5] Use of higher doses established on the basis of liver biopsy findings, serum HCV antibodand longer duration of therapy have been attempted to in-ies, and abnormal serum transaminase levels. Enrollment was crease the response rates, but the data are inconclusive.…”

Section: Methodsmentioning

confidence: 99%

A prospective, randomized trial comparing lymphoblastoid to recombinant interferon alfa 2a as therapy for chronic hepatitis C

et al. 1996

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the development of IFN-neutralizing antibodies. [12][13][14] TheoretTo compare the long-term effectiveness and tolerabilically, these risks might be enhanced by long-term adminity of lymphoblastoid interferon (IFN-aN1) and recombiistration of a single type of IFN and mitigated by the adminnant interferon alfa 2a (IFN-a2a) in patients with istration of different types of IFN. Lymphoblastoid IFN chronic hepatitis caused by hepatitis C virus (HCV), 234 (IFN-aN1), a mixture of 22 interferons, 15 was shown to induce consecutive patients with HCV-related chronic hepatitis a response in 40% of nonresponders to recombinant IFN 16,17 were randomized prospectively to receive titrated doses and resulted in a complete response in all patients with hepa-(starting dose Å 6 million units [MU]) of IFN-a2a (n Å titis C who relapsed during treatment with recombinant 118) or IFN-aN1 (n Å 116) for 12 months. HCV RNA was IFN. 14 To assess whether treatment of hepatitis C can be detected by reverse-transcription polymerase chain reimproved by using lymphoblastoid IFN, we have conducted action (RT-PCR), quantified by branched-DNA (bDNA) a prospective randomized comparative trial in which patients assay, and genotyped by reverse hybridization assay.with chronic hepatitis caused by HCV were randomized to Thirty-one patients in the IFN-a2a group and 28 in the either recombinant IFN-a2a or lymphoblastoid IFN-aN1. IFN-aN1 group (total, 59 [25%] had normal transami-To avoid potential bias caused by insufficient dose or duranases and undetectable HCV RNA by RT-PCR after 12 tion of therapy, we elected to treat patients for 12 months months of therapy, but only 19 in the first group and 20and modify the dose according to the alanine transaminase in the second group (total, 39 [17%]) had biochemical (ALT) response. The initial dose was 6 MU. To gain insight and virological responses 12 months after treatment was on the cost-effectiveness of treatment regimens, we analyzed discontinued. The two treatment groups differed in the tolerability and cost of the two treatments, as well as terms of prevalence of major drug-related adverse reacclinical and virological predictors of treatment outcome that tions (23% vs. 37%, P Å .025). The mean total dose per could be used for refining therapy duration or dosage. size made it possible to perform an interim analysis when 50% of the patients had been enrolled. It was planned that the trial would Less than 25% of the patients with chronic hepatitis C be discontinued at that time if the difference in response rates beachieve sustained biochemical responses with undetectable se-tween the two treatments was outside the confidence interval (CI) related to a type I error equal to 0.025 (3.8%-36.2%). and longer duration of therapy have been attempted to in-ies, and abnormal serum transaminase levels. Enrollment was crease the response rates, but the data are inconclusive. [4][5][6][7][8][9] stopped in November 1992 when 258 patients had been recruited, Nonresponse or loss of response during IFN therapy could and...

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Section: Methodsmentioning

confidence: 99%

A prospective, randomized trial comparing lymphoblastoid to recombinant interferon alfa 2a as therapy for chronic hepatitis C

et al. 1996

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“…Currently, interferon (IFN) is the only drug that induces viral clearance and marked biochemical and histological improvement (1)(2)(3)(4)(5)(6). During IFN administration, the serum level of hepatitis C virus (HCV)-RNAwas negative by reverse transcription nested polymerase chain reaction (RT-PCR), in about 50-80%patients.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Changes of the Nonstructural 5A GENE by Prolonged Interferon Therapy for Patients with Hepatitis C Virus genotype 1b and a High Level of Serum HCV-RNA.

et al. 1999

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Object: The aim of this study was to examine the efficacy and the changes of amino acid sequences of the interferon sensitivity-determining region (ISDR) by prolonged interferon (IFN) treatment in patients who have serum hepatitis C virus (HCV)-genotype lb and a high level of serum HCV-RNA. Methods: Inclusion criteria were biopsy-proven chronic hepatitis, positive HCV-RNA,and an abnormal serum aminotransferase level. Twenty-five patients received 6 MU of natural IFN-oc daily for 8 weeks, followed by three times weekly for 40 weeks (1,056 MU). One patient was withdrawn from the study due to IFN side effects. Therefore, the remaining 24 patients (group 1) were studied the efficacy of IFN administration and changes of ISDR. As a control, 22 patients (group 2) treated with natural IFN-a for 24 weeks for the same period were studied retrospectively.Patients were defined as complete responders (CR) if serum HCV-RNA levels were negative for 6 months after IFN therapy. Results: According to this criterion, CR was 25% (6/24) in group 1 and 9.1% (2/22) in group 2. The normalization rates of alanine aminotransferease (ALT) for six months after termination of IFN was 41 % (10/24) in group 1 and 18.2% (4/22) in group 2. Regarding the changes of ISDR in patients with no CR, the change rates ofISDR were 16.7% (3/18) in group 1 and 10% (2/20) in group 2. Conclusion: We concluded that prolonged IFN therapy was effective for patients with HCV-genotype lb and a high level of serum HCV-RNA. (Internal Medicine 38: 461-466, 1999)

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“…According to our estimation of the carcinogenesis rates in untreated patients with chronic hepatitis C, 7 5-year, 10-year, and 15-year rates were 4.8%, 13.6%, and 26.0%, respectively. Because life expectancy of patients with HCV-related cirrhosis is largely influenced by development of HCC in the clinical course, and because an effective and truly curative therapy for HCC still remains limited at best, primary prevention of HCC in patients with chronic liver disease is of great importance.Interferon (IFN) is effective in eliminating HCV and in reducing serum alanine transaminase (ALT) in some patients with chronic hepatitis C. [8][9][10][11] The response to IFN therapy is related to factors including HCV subtype, serum concentration of HCV, IFN treatment schedule, and liver histology. 11-14 A Japanese trial of IFN for patients with HCV-related cirrhosis showed that IFN therapy decreased the HCC appearance rate through the disappearance of HCV RNA.…”

mentioning

confidence: 99%

“…Interferon (IFN) is effective in eliminating HCV and in reducing serum alanine transaminase (ALT) in some patients with chronic hepatitis C. [8][9][10][11] The response to IFN therapy is related to factors including HCV subtype, serum concentration of HCV, IFN treatment schedule, and liver histology. [11][12][13][14] A Japanese trial of IFN for patients with HCV-related cirrhosis showed that IFN therapy decreased the HCC appearance rate through the disappearance of HCV RNA.…”

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confidence: 99%

Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: A long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis

et al. 1999

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The activity of interferon (IFN) is not elucidated from the viewpoint of cancer prevention in chronic hepatitis C patients en masse. The hepatocellular carcinogenesis rate was analyzed statistically in 1,643 patients with chronic hepatitis C: 1,191 patients with IFN therapy and 452 without IFN therapy. Hepatocellular carcinogenesis rates in the treated and untreated groups were 2.1% and 4.8% at the end of the 5th year, and 7.6% and 12.4% at the 10th year, respectively (P ‫؍‬ .0036). Multivariate analysis showed that IFN slightly decreased the risk of carcinogenesis by 33%, compared with that of untreated patients (P ‫؍‬ .14), adjusting for the confounding effects of age, fibrotic stage, gender, and ␥-glutamyl transpeptidase (GGTP) value. Until recently, hepatitis C virus (HCV) has been reported to be a causative agent of hepatocellular carcinoma (HCC) aside from hepatitis B virus. [1][2][3][4] In two cohort studies from Tokyo 5 and Osaka 6 of Japanese patients with cirrhosis, the cumulative appearance rates of HCC at 3, 5, 10, and 15 years were respectively, 12.5%, 19.4%, 44.3%, and 58.2%. HCC occurred more frequently (75.2% at 15 years) in those patients with only HCV antibodies at enrollment than in those with only hepatitis B surface antigen (27.2%). According to our estimation of the carcinogenesis rates in untreated patients with chronic hepatitis C, 7 5-year, 10-year, and 15-year rates were 4.8%, 13.6%, and 26.0%, respectively. Because life expectancy of patients with HCV-related cirrhosis is largely influenced by development of HCC in the clinical course, and because an effective and truly curative therapy for HCC still remains limited at best, primary prevention of HCC in patients with chronic liver disease is of great importance.Interferon (IFN) is effective in eliminating HCV and in reducing serum alanine transaminase (ALT) in some patients with chronic hepatitis C. [8][9][10][11] The response to IFN therapy is related to factors including HCV subtype, serum concentration of HCV, IFN treatment schedule, and liver histology. 11-14 A Japanese trial of IFN for patients with HCV-related cirrhosis showed that IFN therapy decreased the HCC appearance rate through the disappearance of HCV RNA. 15 However, there has been no report about the anticarcinogenic activity of IFN in patients with chronic hepatitis type C, comparing a large number of untreated patients. To elucidate whether IFN suppresses the carcinogenesis rate in patients with chronic hepatitis C, we studied a total of 1,191 patients with IFN therapy compared with 452 patients without treatment, adjusting background features using multivariate analysis. One of the principal aims of our study was therefore to show a role of IFN in cancer prevention in chronic hepatitis type C en masse: To what extent could IFN decrease the carcinogenesis rate from chronic hepatitis C in society? The other aim was to assess a possible mechanism, if any, of cancer prevention by IFN. PATIENTS AND METHODSStudy Population. A total of 1,643 patients with chronic hepatitis ...

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Comparison of 1 or 3 MU of interferon alfa-2b and placebo in patients with chronic non-A, non-B hepatitis

Cited by 243 publications

References 15 publications

A prospective, randomized trial comparing lymphoblastoid to recombinant interferon alfa 2a as therapy for chronic hepatitis C

A prospective, randomized trial comparing lymphoblastoid to recombinant interferon alfa 2a as therapy for chronic hepatitis C

Efficacy and Changes of the Nonstructural 5A GENE by Prolonged Interferon Therapy for Patients with Hepatitis C Virus genotype 1b and a High Level of Serum HCV-RNA.

Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: A long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis

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