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

Hawkins, Amanda; Davidson, Fiona; Simmonds, Peter

doi:10.1128/jcm.35.1.187-192.1997

Cited by 164 publications

(73 citation statements)

References 31 publications

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“…A good correlation was observed when viral load was assessed using serum or plasma samples, obtained from the same blood withdrawal and run at the same time (Spearman correlation r ϭ .82). These results are in keeping with previous findings, 16,18 while they do not confirm other data obtained with a competitive, home-made quantitative test, 17 underlying the fact that different technical approaches can influence final results.…”

Section: Serum Hcv-rna Levelssupporting

confidence: 75%

“…This is likely a result of a better efficiency of detection of genotype 1 by the current version of the assay. 6,18 In conclusion, long-term monitoring of viral replication showed that HCV RNA is relatively stable over time in asymptomatic HCV carriers, while a low number of viremic flares can occur over a year in patients with biochemical activity of liver disease.…”

Section: Discussionmentioning

confidence: 86%

“…The observed differences are likely the result of the underestimation of HCV-RNA load in viral types 2 and 3 by the version of the assay used. 6,18 NOTE. ⌬ represents the difference between the maximum and minimum value of HCV RNA measured over time in each individual patient.…”

Section: Serum Hcv-rna Levelsmentioning

confidence: 99%

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Hepatitis C Virus Rna Profiles in Chronically Infected Individuals: Do They Relate to Disease Activity?

et al. 1999

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Fluctuations of hepatitis C virus (HCV)-RNA serum levels were monitored in a multicenter study in 76 chronic HCV carriers who had been followed longitudinally without receiving antiviral therapy to assess their relation with the course of liver disease activity. Forty-four patients had normal transaminases over more than 2 years, while 32 additional patients had fluctuating levels. Viral load was measured in serial serum samples prospectively collected for 10 to 12 months in 54 patients and in sera stored yearly up to 8 years in an additional 22 patients. In patients tested monthly, a lesser extent of fluctuations was detected in cases with constantly normal transaminases as compared with those with fluctuating transaminases. In the former group, the mean difference between maximum and minimum values observed in each individual patient was 0.7 Log, while in the latter group, it was 1.3 Log (P ‫؍‬ .0004). Most of these patients experienced, on average, three peaks of viremia over 1 year. The range of variation observed upon yearly testing was between 0.2 and 2.2 Log and did not reach statistical significance between the two groups. In conclusion, a careful viral replication profile can be achieved only by monthly testing, because longer time intervals could miss viremia fluctuations. HCV-RNA levels are more stable in asymptomatic HCV carriers than in patients with biochemical activity of liver disease. (HEPATOLOGY 1999;29: 585-589.)Chronic infection with hepatitis C virus (HCV) is characterized by persistent viremia. HCV RNA is usually detected in serum by sensitive polymerase chain reaction (PCR)-based techniques and has become a useful tool for diagnosis and monitoring. Besides methods for qualitative detection of viremia, a number of procedures to quantify serum HCV RNA have been developed, including end-point dilution PCR, 1 competitive PCR, 2,3 isothermal nucleic acid amplification, 4 and signal-amplification branched DNA. 5 Routine use of these techniques in a wide clinical setting is hampered by problems of specificity and sensitivity, lack of reproducibility, poor standardization, and high cost. 6 Recently, methods for quantitative assessment of HCV-RNA levels have become commercially available and are being extensively evaluated in clinical studies, particularly in patients treated with interferons and antivirals. 7 Little is known about viral kinetics in untreated patients, because most evaluations of the level of viremia are based on single determinations. If wide spontaneous fluctuations occur, they could mimic treatment-induced effects or lead to under-or overestimate baseline values. In a few published studies, different time intervals have been evaluated and discordant conclusions have been reported. Either trivial or consistent differences of viral load over time have been described after observation periods ranging from days to months. [8][9][10][11][12] To assess the spontaneous behavior of serum HCV-RNA levels over a reasonable length of time upon close observation, we monitored chronic HCV car...

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Section: Serum Hcv-rna Levelssupporting

confidence: 75%

Section: Discussionmentioning

confidence: 86%

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Hepatitis C Virus Rna Profiles in Chronically Infected Individuals: Do They Relate to Disease Activity?

et al. 1999

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“…3,4,10 General application may be difficult due to the previous lack of standardization of HCV-RNA detection methods. [11][12][13][14] The HCV-RNA detection assay applied in several pivotal trials (Superquant; NGI, Los Angeles, CA) is not generally available outside the United States. Furthermore, current algorithms for treatment of chronic hepatitis C may have been influenced by marketing interests of pharmaceutical companies who designed and analyzed these multicenter trials.…”

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confidence: 99%

Prediction of treatment outcome in patients with chronic hepatitis C: Significance of baseline parameters and viral dynamics during therapy

et al. 2003

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In patients with chronic hepatitis C virus (HCV) infection scheduled for a 48-week treatment period, premature discontinuation of treatment was previously recommended if HCV-RNA levels remained detectable at week 24 of therapy. Considering the number of side effects and treatment costs, measurement of initial viral decline during therapy may identify virologic nonresponse earlier than 24 weeks. We retrospectively analyzed 260 European patients treated with standard or pegylated interferon alfa (IFN-␣) and ribavirin for 24 to 48 weeks. Early prediction of virologic response by HCV-RNA decline at weeks 4 and 12 (Versant Quantitative [branched DNA (bDNA) 3.0]; Bayer Diagnostics, Emeryville, CA; and Qualitative [transcription-mediated amplification (TMA)] HCV RNA assay; Bayer Diagnostics) as well as clinical, biochemical, virologic, and histologic baseline parameters were analyzed by logistic regression and receiver operating characteristic (ROC) curves. A viral load at treatment week 4 above 450,000 IU/mL and at week 12 above 30,000 IU/mL was 100% predictive for virologic nonresponse in all patients. From multivariate logistic regression analysis of all patients, independent predictors for sustained virologic response were: genotypes 2 and 3 (P < .0001), a low baseline gamma-glutamyltransferase (GGT) level (P < .0001), a high baseline alanine aminotransferase level (P ‫؍‬ .002), and a low baseline viral load (P ‫؍‬ .04). None of the latter 3 factors were predictive for sustained virologic response when analysis was restricted to the subgroup of genotypes 2-and 3-infected patients. In conclusion, virologic nonresponse can be predicted early at week 12 of treatment independent from the applied therapeutic regimen based on a cutoff level for HCV RNA of 30,000 IU/mL. This algorithm recognizes 53.7% of nonresponders previously identified at week 24 of treatment. (HEPATOLOGY 2003;37:600-609.)

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“…In particular, the detections of HCV RNA by commercially available (semi)quantitative assays have some limitations as to their sensitivity or variation coefficient, 7,8 and may amplify different viral genotypes with a different efficiency. 9 Moreover, all diagnostic assays are aimed at detecting the genomicstrand HCV RNA; therefore, they may also detect the virions' RNA trapped in the liver biopsy specimens at the time of sampling. On the other hand, the specificity of the detection of the minus-strand HCV RNA (the putative HCV replication intermediate RNA) has been repeatedly questioned.…”

mentioning

confidence: 99%

Detection of Genomic– and Minus–Strand of Hepatitis C Virus Rna in the Liver of Chronic Hepatitis C Patients by Strand–Specific Semiquantitative Reversetranscriptase Polymerase Chain Reaction

Negro

Krawczynski

Quadri³

et al. 1999

Hepatology

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Studies aimed at correlating the intrahepatic hepatitis C virus (HCV)-RNA level and anatomo-clinical features have been difficult because of sensitivity and specificity shortcomings of available techniques. We titered the genomic-and minus-strand HCV RNAs by a strand-specific, semiquantitative, genotype-independent reverse-transcriptase polymerase chain reaction (RT-PCR) in the liver tissue of 61 patients with chronic hepatitis C. Findings were correlated with the levels of HCV RNA in the serum, the HCV genotype, the expression of intrahepatic HCV antigens, the histological activity (using separate scores for the lobular and the portal/periportal necroinflammatory activity and for the fibrosis), and the response to interferon alfa (IFN-␣) treatment. Genomic-and minus-strand HCV RNA were detected in 59 and 57 liver specimens, respectively. The pathogenesis of the hepatitis C virus (HCV)-associated liver disease is believed to be mainly mediated by the immune system. 1 However, some studies have shown a direct correlation between the viremia level and the hepatitis activity, 2-6 thus suggesting a direct cytopathogenic effect of HCV on hepatocytes. Ideally, the correlation between HCV replicative levels and pathological findings (as well as with other clinical features) should rely on the quantitation of HCV RNA (or antigens) in the liver. Unfortunately, correlative studies between the semiquantitation of HCV replicative levels in the liver and the disease activity have been difficult because of the technical shortcomings of the published techniques. In particular, the detections of HCV RNA by commercially available (semi)quantitative assays have some limitations as to their sensitivity or variation coefficient, 7,8 and may amplify different viral genotypes with a different efficiency. 9 Moreover, all diagnostic assays are aimed at detecting the genomicstrand HCV RNA; therefore, they may also detect the virions' RNA trapped in the liver biopsy specimens at the time of sampling. On the other hand, the specificity of the detection of the minus-strand HCV RNA (the putative HCV replication intermediate RNA) has been repeatedly questioned. 10 Suitably modified reverse-transcriptase polymerase chain reaction (RT-PCR)-based assays of sufficient specificity are now available 10 and can be applied to the analysis of clinical specimens.We have previously detected the intrahepatic minus-strand HCV RNA by a semiquantitative, strand-specific RT-PCR in liver transplant recipients. 11 In that study, we showed a lack of correlation between the HCV-RNA level in the serum, the genomic-and the minus-strand HCV-RNA titers in the liver on the one hand, and the histological grading and staging of the liver disease on the other. 11 In the present work, we applied the same assay to a series of liver biopsy specimens taken from chronic hepatitis C patients. Our aim was to assess whether clinically significant correlations could be established between the intrahepatic titers of either strand of HCV RNA and some histopathological and clinica...

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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

Cited by 164 publications

References 31 publications

Hepatitis C Virus Rna Profiles in Chronically Infected Individuals: Do They Relate to Disease Activity?

Hepatitis C Virus Rna Profiles in Chronically Infected Individuals: Do They Relate to Disease Activity?

Prediction of treatment outcome in patients with chronic hepatitis C: Significance of baseline parameters and viral dynamics during therapy

Detection of Genomic– and Minus–Strand of Hepatitis C Virus Rna in the Liver of Chronic Hepatitis C Patients by Strand–Specific Semiquantitative Reversetranscriptase Polymerase Chain Reaction

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