Effect of interferon administration on serum hepatitis C virus RNA in patients with chronic hepatitis C

Chayama, Kazuaki; Saitoh, Satoshi; Arase, Yasuji; Ikeda, Kenji; Matsumoto, Toyomi; Shibata, Yoko; Kobayashi, Mariko; Unakami, Masamitsu; Morinagaa, Tsuto; Kumada, Hiromitsu

doi:10.1002/hep.1840130606

Cited by 174 publications

(3 citation statements)

References 14 publications

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“…A number of investigators have reported that serum HCV RNA became undetectable or titers diminished in the patients responding to alpha interferon therapy (37,53,121,221,345,347). During relapse, serum HCV RNA once again emerged.…”

Section: Treatmentmentioning

confidence: 99%

Hepatitis C: progress and problems

Cuthbert

1994

Clin Microbiol Rev

153

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The hepatitis C virus (HCV), a single-stranded RNA virus, is the major cause of posttransfusion hepatitis. HCV isolates differ in nucleotide and amino acid sequences. Nucleotide changes are concentrated in hypervariable regions and may be related to immune selection. In most immunocompetent persons, HCV infection is diagnosed serologically, using antigens from conserved regions. Amplification of RNA may be necessary to detect infection in immunosuppressed patients. Transmission by known parenteral routes is frequent; other means of spread are less common and may represent inapparent, percutaneous dissemination. Infection can lead to classical acute hepatitis, but most infected persons have no history of acute disease. Once infected, most individuals apparently remain carriers of the virus, with varying degrees of hepatocyte damage and fibrosis ensuing. Chronic hepatitis may lead to cirrhosis and hepatocellular carcinoma. However, disease progression varies widely, from less than 2 years to cirrhosis in some patients to more than 30 years with only chronic hepatitis in others. Determinants important in deciding outcome are unknown. Alpha interferon, which results in sustained remission in selected patients, is the only available therapy. Long-term benefits from such therapy have not been demonstrated. Prevention of HCV infection by vaccination is likely to be challenging if ongoing viral mutation results in escape from neutralization and clearance.

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Section: Treatmentmentioning

confidence: 99%

Hepatitis C: progress and problems

Cuthbert

1994

Clin Microbiol Rev

153

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“…In an attempt to dethat induces viral clearance and marked biochemical velop a new therapeutic strategy that may reduce reand histological improvement. 9,10 Reappearance of the lapse and cure the disease, we evaluated the effect of virus and increase of alanine transaminase (ALT) accorticosteroid priming on lymphoblastoid interferon tivity, however, have been reported in more than half of alfa in an open randomized clinical trial. The level of treated patients.…”

mentioning

confidence: 99%

A pilot study of corticosteroid priming for lymphoblastoid interferon alfa in patients with chronic hepatitis C

Chayama¹,

Tsubota²,

Hashimoto³

et al. 1996

Hepatology

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Interferon treatment reduces the serum level of hepatitis C virus (HCV) and improves inflammatory activity, but relapse is frequently observed. In an attempt to develop a new therapeutic strategy that may reduce relapse and cure the disease, we evaluated the effect of corticosteroid priming on lymphoblastoid interferon alfa in an open randomized clinical trial. The level of HCV RNA increased significantly during corticosteroid priming (from 5.60 [median] to 21.0 x 10(5) Eq/mL; P = .0004) but decreased to the pretreatment level 4 weeks after cessation of corticosteroid (7.0 x 10(5) Eq/mL; P = .07). Sustained normalization of alanine transaminase (ALT) level and virus clearance, confirmed by negative results for HCV RNA using reverse-transcription nested polymerase chain reaction (PCR), were observed over a period of 6 months in 8 of 19 (42.1%) corticosteroid-primed patients, compared with 6 of 19 patients (31.6%) treated with interferon only. A "rebound" of ALT after the withdrawal of corticosteroid was observed in only 2 of 19 patients primed with corticosteroid, but both showed sustained responses. Multivariate analysis for factors predictive of the sustained response indicated that HCV titers measured immediately before interferon therapy and HCV genotype were statistically significant (P = .006 and P = .025, respectively). Our results indicated that corticosteroid priming has a marginal benefit over treatment with interferon alone and that large-scale clinical trials are necessary to determine whether interferon with corticosteroid priming is more effective than interferon alone.

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“…Amplification of hepatitis C virus (HCV) RNA by PCR has been an indispensable tool in studies of the natural history of HCV infections in addition to serving as a means for the early detection of viral infection (5,7,16,17). Because it provides direct evidence for the presence of viral nucleic acid, PCR has also played an important role in evaluating the efficacy of antiviral therapy (3,6,18). For these and other applications, the accuracy of the PCR results is crucial.…”

mentioning

confidence: 99%

Detection of hepatitis C virus RNA by a combined reverse transcription PCR assay: comparison with nested amplification and antibody testing

et al. 1995

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Many of the current reverse transcription (RT)-PCR assays for the detection of hepatitis C virus (HCV) RNA are multistep processes which use multiple enzymes and buffers. The assays are also often suboptimal, requiring nested amplification to achieve the desired levels of sensitivity. As a result, these assays are cumbersome and prone to false-positive results. The susceptibility to contamination is further aggravated by the lack of carryover controls. We have previously reported the development of a combined RT-PCR assay for HCV RNA detection which is sensitive and simple to perform. We have since successfully integrated dUTPuracil-N-glycosylase carryover prevention into the combined assay. Restriction of as much as 0.5 l of deoxyuridine-containing amplification products has been achieved. The performance of the improved combined assay was compared directly with conventional nested RT-PCR and antibody detection. The combined assay was found to have sensitivity similar to that of nested RT-PCR in detecting HCV RNA from HCV antibody-positive specimens. In an analysis of hepatitis B virus antibody-positive specimens, nested amplification had false-positive rates ranging from 8 to 31%, while no false-positive results were seen with the combined assay. In comparison with serological methods, the combined assay had specificity and sensitivity of 100 and 95%, respectively.

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Effect of interferon administration on serum hepatitis C virus RNA in patients with chronic hepatitis C

Cited by 174 publications

References 14 publications

Hepatitis C: progress and problems

Hepatitis C: progress and problems

A pilot study of corticosteroid priming for lymphoblastoid interferon alfa in patients with chronic hepatitis C

Detection of hepatitis C virus RNA by a combined reverse transcription PCR assay: comparison with nested amplification and antibody testing

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