Usefulness of HCV-RNA counts by the method of HCV-bDNA probe in interferon retreatment for patients with HCV-RNA positive chronic hepatitis C

Arase, Yasuji; Kumada, Hiromitsu; Chayama, Kazuaki; Matsumoto, Naoya; Tsubota, Akihito; Koida, Isao; Kobayashi, Masahiro; Suzuki, Yoshiyuki; Ikeda, Kazumasa; Saitoh, Satoshi

doi:10.1016/0928-4346(95)00208-z

Cited by 7 publications

(3 citation statements)

References 12 publications

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“…Alternatively, NR patients had higher viral loads and/ or were treated with IFN at less the ideal dose at the second therapy, compared with the initial therapy. The two factors of viral load and IFN total dose reported previously as predictors of efficacy of IFN therapy might also influence the efficacy of IFN retreatment [Arase et al, , 1995, rather than only amino acid substitution patterns of NS5A. The number of patients with the second IFN therapy was very small, and further studies of a large group of patients infected with low viral load of genotype 2a (viral load with PCR matched more exactly) are required to clarify the true relationship between amino acid substitutions of NS5A and viral sensitivity to IFN monotherapy.…”

Section: Discussionmentioning

confidence: 98%

Association of amino acid substitution pattern in nonstructural protein 5A of hepatitis C virus genotype2a low viral load and response to interferon monotherapy

Akuta

Suzuki

Tsubota

et al. 2003

Journal of Medical Virology

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Patients with low titer (<0.5 mEq/ml) of hepatitis C virus (HCV) genotype 2a achieve high and sustained response (SR) rates to interferon (IFN) monotherapy, but we also encounter patients who are resistant to therapy. We explored the relationship between response to IFN and virological differences in such patients. We evaluated 159 consecutive naive patients with low titer of HCV genotype 2a who received IFN monotherapy. A case-control study matched for age, sex, and viral load was conducted to examine the substitution patterns in amino acid positions (amino acids) 2163-2254 of nonstructural (NS) 5A between nonresponders to ideal IFN dose (>/=500 million units) (nonresponders; NR) and responder to less than ideal dose. Overall, 82.4% achieved SR. The substitution numbers in amino acids 2193-2254 were higher in SR than NR patients (P< 0.05). High proportions of patients with substitution at amino acid 2205 (mainly threonine [T] instead of alanine [A]), dual amino acids 2169 and 2205 (mainly A-T instead of T-A), and those without substitution at amino acids 2227 were NR (P < 0.05). Four of 7 NR patients achieved SR after receiving a second course of IFN. Their amino acids patterns at positions probably associated with sensitivity to IFN did not change at the start of initial and second therapies except for one patient, and they had lower viral load and were treated with higher IFN dose in the second course compared with the initial course. Our results suggest that substitution patterns in NS5A in patients with low titer of HCV genotype 2a may affect their response to IFN, but the response to therapy may be affected by mechanisms other than substitutions in this region.

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Section: Discussionmentioning

confidence: 98%

Association of amino acid substitution pattern in nonstructural protein 5A of hepatitis C virus genotype2a low viral load and response to interferon monotherapy

Akuta

Suzuki

Tsubota

et al. 2003

Journal of Medical Virology

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“…Quantitation of hepatitis C virus (HCV) RNA sequences in plasma and more recently in liver has become a valuable diagnostic tool for the pretreatment evaluation of patients undergoing treatment with interferon and in the subsequent monitoring of their response (8). For example, several studies have described a decreased likelihood of achieving a long-term response to interferon treatment in individuals with a high pretreatment virus load in plasma (1,12,(19)(20)(21)(22)28). This difference was shown to be independent of other pretreatment variables that also influenced response, such as severity of liver disease and virus genotype (19)(20)(21)28).…”

mentioning

confidence: 99%

Comparison of plasma virus loads among individuals infected with hepatitis C virus (HCV) genotypes 1, 2, and 3 by quantiplex HCV RNA assay versions 1 and 2, Roche Monitor assay, and an in-house limiting dilution method

1997

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The accuracy of different methods for the quantitation of hepatitis C virus in plasma was measured with samples from individuals infected with different genotypes and by using RNA transcripts of predetermined concentrations. Highly reproducible results were observed upon repeat testing of samples by both the original version of the Chiron branched-DNA (bDNA) assay (Quantiplex RNA assay; bDNA-1) and the currently available version (Quantiplex HCV RNA 2.0 assay; bDNA-2). A greater variability was observed in the Roche Monitor assay (correlation coefficient of 0.537, compared with 0.942 and 0.964 for the bDNA-1 and bDNA-2 assays, respectively). Significant differences in the efficiency of detection of genotypes 1, 2, and 3 were observed for the bDNA-1 and Roche Monitor assays, whereas the bDNA-2 assay and nested PCR at limiting dilution were able to quantify genotypes with equal sensitivity. By quantifying RNA transcripts of different genotypes, the sensitivities of the Roche Monitor assay for sequences of the type 2 and type 3 transcripts were estimated to be 11 and 8% of those achieved for genotype 1. When correction factors based upon these results and those from quantitation of circulating viral RNA sequences in samples from blood donors were used, the genotypespecific differences in virus load in samples from blood donors were no longer observed, consistent with previous studies with corrected values from the bDNA-1 assay. These results suggest that many of the previous studies evaluating the effect of genotype and virus load on the response to interferon using methods such as the Roche Monitor assay and other competitive PCR methods require reinterpretation. Differences in efficiency of quantitation should be taken into account in future investigations of the relationship between genotype and virus load.

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“…3,5 Some reports show that this assay is useful as a marker for interferon therapy. 8 We reported 9 that HCV genotypes should be considered when this assay is used because it tends to show lower than actual HCV-RNA counts in HCV genotypes 2a and type 2b, since the probe used for the assay (ver 1) is a combination of sequences from the 5Ј-noncoding region and the core region of HCV genotype 1a (type 1a). This problem with ver 1 was corrected in a newly developed ver 2 by adding probes from the highly variable portion of the 5Ј-noncoding region and core region.…”

Section: Introductionmentioning

confidence: 99%

Usefulness of hepatitis C virus RNA counts by second generation HCV bDNA-probe in chronic hepatitis C based on the HCV genotype

Kobayashi

Kumada

Arase

et al. 1998

Journal of Gastroenterology

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Detection of hepatitis C virus (HCV) RNA by a second generation (ver 2) HCV bDNA-probe method (bDNA-probe) was compared with detection by the first generation (ver 1) assay. The two assays were performed simultaneously with the same serum samples of HCV genotypes 1b, 2a, 2b, 3a, and 3b. The positive rates with ver 1 were 82% for HCV genotype 1b (type 1b), 57.6% for HCV genotype 2a (type 2a), 75.0% for HCV genotype 2b (type 2b), 55.6% for HCV genotype 3a (type 3a), and 93.8% for HCV genotype 3b (type 3b). The positive rates with ver 2 were 95.0% for type 1b, 93.9% for type 2a, 83.3% for type 2b, 100% for type 3a, and 93.8% for type 3b. With Fisher's exact test, the detection rate for type 2a was significantly higher (P = 0.001) with ver 2 than with ver 1. We obtained regression lines using the HCV counts measured by bDNA-probe on the y axis and the HCV counts obtained by an HCV reverse transcriptase (RT)-competitive polymerase chain reaction method (competitive PCR) on the x axis. The gradients for types 1b, 2a, and 3b were greater with ver 2 compared to ver 1. The gradients for types 2a and 3b were the highest: for type 2a, y = 0.135x + 0.6 with ver 1 and y = 0.248x + 0.1 with ver 2; for type 3b, y = 0.366x + 0.1 with ver 1 and y = 0.727x + 0.3 for ver 2. In addition, HCV-RNA counts for all the genotypes tested in this study were significantly higher with ver 2 than with ver 1. Hence, we conclude that ver 2 of the bDNA-probe measures HCV-RNA counts closer to those obtained with competitive PCR than the ver 1 assay.

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Usefulness of HCV-RNA counts by the method of HCV-bDNA probe in interferon retreatment for patients with HCV-RNA positive chronic hepatitis C

Cited by 7 publications

References 12 publications

Association of amino acid substitution pattern in nonstructural protein 5A of hepatitis C virus genotype2a low viral load and response to interferon monotherapy

Association of amino acid substitution pattern in nonstructural protein 5A of hepatitis C virus genotype2a low viral load and response to interferon monotherapy

Comparison of plasma virus loads among individuals infected with hepatitis C virus (HCV) genotypes 1, 2, and 3 by quantiplex HCV RNA assay versions 1 and 2, Roche Monitor assay, and an in-house limiting dilution method

Usefulness of hepatitis C virus RNA counts by second generation HCV bDNA-probe in chronic hepatitis C based on the HCV genotype

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