Quantification and genotyping of serum HCV-RNA in patients with chronic hepatitis C undergoing interferon treatment (original) (raw)
Related papers
International Hepatology Communications
We analyzed serum HCV-RNA levels using a newly developed quantitative nucleic acid hybridization (branched DNA probe) assay in 32 Japanese patients with chronic hepatitis C treated with p-interferon (/.I-IFN). The branched DNA probe assay was less sensitive than the polymerase chain reaction (PCR) method but it provided easy and accurate quantitative analysis of HCV-RNA levels in several samples. Eleven of 32 (34%) patients had a complete response (CR) to IFN treatment, defined as normalization of ALT levels. Six patients (19%) had a partial response (PR) and 15 (47%) had no response (NR). In only one of 11 (9%) patients with CR, the pre-treatment HCV-RNA level was marginally more than the detectable limit of 350 kequivalents/ml (keq/ml). However, serum HCV-RNA levels were detectable in four of six patients (67%) with PR and 13 of 15 (87%) patients with NR. There was a significant difference in HCV-RNA levels between CR and NR groups (9% vs. 87%, P < 0.01) using this method. We could not find a significant difference in the proportion of different genotypes of HCV-RNA between CR and NR groups. We conclude that determination of serum HCV-RNA levels prior to IFN treatment using a branched DNA probe assay is very useful in predicting the effect of IFN treatment.
Serial assay of hepatitis C virus RNA in serum for predicting response to interferon-a therapy
Digest Dis Sci, 1995
To determine whether the loss of serum hepatitis C virus RNA (HCV-RNA) early in interferon therapy would indicate a sustained response to this agent, we detected serum HCV-RNA successively during and after therapy. Serum samples for detection of HCV-RNA were obtained serially from 36 patients with chronic hepatitis C treated with interferon-et. In 28 of these patients, results of the assay were compared with genotypes and quantitative levels of HCV-RNA in serum before therapy. HCV-RNA was detected by a reverse transcription polymerase chain reaction using the 5'-noncoding region as a primer. Genotypes were determined by using type-specific primers, and serum levels of HCV-RNA were determined by a competitive reverse transcription polymerase chain reaction (RT-PCR). HCV-RNA disappeared from serum in eight of 10 responders (80%), but in only one of the 26 nonresponders (3.8%) at the second week of therapy (P < 0.0005). The time until the disappearance of HCV-RNA was correlated with the serum level of HCV-RNA present before therapy (P < 0.05). The early disappearance of HCV-RNA from serum during interferon therapy was useful in predicting a sustained response in patients with chronic hepatitis C.
Serial assay of hepatitis C virus RNA in serum for predicting response to interferon-α therapy
Digestive Diseases and Sciences, 1995
To determine whether the loss of serum hepatitis C virus RNA (HCV-RNA) early in interferon therapy would indicate a sustained response to this agent, we detected serum HCV-RNA successively during and after therapy. Serum samples for detection of HCV-RNA were obtained serially from 36 patients with chronic hepatitis C treated with interferon-et. In 28 of these patients, results of the assay were compared with genotypes and quantitative levels of HCV-RNA in serum before therapy. HCV-RNA was detected by a reverse transcription polymerase chain reaction using the 5'-noncoding region as a primer. Genotypes were determined by using type-specific primers, and serum levels of HCV-RNA were determined by a competitive reverse transcription polymerase chain reaction (RT-PCR). HCV-RNA disappeared from serum in eight of 10 responders (80%), but in only one of the 26 nonresponders (3.8%) at the second week of therapy (P < 0.0005). The time until the disappearance of HCV-RNA was correlated with the serum level of HCV-RNA present before therapy (P < 0.05). The early disappearance of HCV-RNA from serum during interferon therapy was useful in predicting a sustained response in patients with chronic hepatitis C.
The American journal of gastroenterology, 2003
The present study was performed to evaluate the impact of the international unit standard for measuring HCV RNA in the management of patients with chronic hepatitis C virus (HCV) infection. The three assays used were Amplicor Monitor PCR, the National Genetics Institute PCR assay, and branched chain DNA. HCV RNA was measured at four time points (baseline, 3 months after the start of therapy, at the end of treatment, and 6 months after discontinuation of therapy) in 106 consecutive patients who received interferon and ribavirin for chronic HCV. The mean age of the patients was 44 yr. Of the patients, 62% were male, 24% were African American, 38% had bridging fibrosis or cirrhosis, and 75% were HCV genotype 1. Of the 424 samples analyzed, 82-89% of values were within 1 log unit and 85-92% were within 2 log units by the various assays. This variability was not dependent upon HCV genotype. HCV RNA was undetectable in 1.4-6.8% of samples when virus was detected by another assay. The mean...
2009
Assessment of the viral load in hepatitis C virus (HCV) genotype 1-infected patients is critical before, during, and after antiviral therapy. In patients achieving a rapid virological response at week 4 of treatment, the viral load at the baseline is considered a predictive criterion of a sustained virological response 24 weeks after the discontinuation of treatment. A >2-log 10 drop in the viral load at week 12 of treatment (early virological response) triggers the continuation of therapy. We organized a multicenter study (MS) for diagnostic laboratories involved in the quantification of HCV RNA. Commercial assays, including two based on real-time reverse transcription-PCR (TaqMan system), and in-house methods, were used by the 61 participants. The overall reproducibility of the commercial quantitative nucleic acid amplification techniques (qNAT) was acceptable. As the intermethod variability among commercial qNAT for HCV RNA was still present, the manufacturers of these test kits should join efforts to harmonize the means of quantification of HCV RNA. This study also shows that caution should be exercised when the baseline viral load is evaluated and when the 2-log 10 reduction after 12 weeks of therapy is interpreted. Finally, this MS confirms the higher sensitivity of the commercial qNAT based on the TaqMan system, making them the elective assays for the monitoring of therapy.
Antiviral Therapy, 2011
Background The development of more sensitive HCV RNA assays might necessitate re-evaluation of the rules for stopping treatment (for example, HCV RNA negativity at week 24 during treatment with pegylated interferon-α and ribavirin for chronic hepatitis C). The aim of this study was to assess discordance between the week 24 HCV RNA test results of two PCR-based assays (Amplicor and Taq-Man) and the transcription-mediated amplification (TMA) HCV RNA qualitative assay. Methods A total of 89 week 24 samples that were negative using PCR-based assays during treatment were retested with the TMA qualitative assay to investigate discordance between tests results. All week 24 samples were HCV RNA negative by Amplicor or by TaqMan. Results Of the 89 patients, 46 (52%) achieved sustained virological response (SVR). Viral breakthrough or relapse occurred in 43 patients (48%). All 89 HCV RNA negative week 24 samples were retested with the qualitative TMA assay. Eleven out of 89 samples had detect...
Journal of Medical Virology, 1995
The use of two new assays was evaluated for predicting the response to interferon (IFN) therapy in patients with chronic hepatitis C. The genotype of hepatitis C virus (HCV) was established by an enzyme-linked immunosorbent assay based on genotype-specific recombinant peptides of the NS4 region (genotyping ELISA). The concentration of HCV RNA was measured by a branched DNA assay (bDNA assay). Seventyeight patients received the same regimen of IFNa2a. Of the 74 patients assessed who completed the program, 38 (51.4%) were responders; i.e., their serum aminotransferase levels remained normal for 6 months or longer after stopping IFN, while 36 (48.6%) were nonresponders. The results of the HCV genotype determined by the genotyping ELISA and by the polymerase chain reaction (PCR) assay based on genotypespecific primers were similar. The serum concentrations of HCV RNA as measured by the bDNA assay and by the competitive PCR assay correlated closely and significantly (r = 0.82, P < 0.001 1. Multiple logistic regression analysis showed that the serum concentration of HCV RNA determined by the bDNA assay, the HCV genotype determined by the genotyping ELISA, and the histology activity index (HAI) of the liver were independently associated with IFN efficacy.
Journal of Medical Virology, 1995
The use of two new assays was evaluated for predicting the response to interferon (IFN) therapy in patients with chronic hepatitis C. The genotype of hepatitis C virus (HCV) was established by an enzyme-linked immunosorbent assay based on genotype-specific recombinant peptides of the NS4 region (genotyping ELISA). The concentration of HCV RNA was measured by a branched DNA assay (bDNA assay). Seventyeight patients received the same regimen of IFNa2a. Of the 74 patients assessed who completed the program, 38 (51.4%) were responders; i.e., their serum aminotransferase levels remained normal for 6 months or longer after stopping IFN, while 36 (48.6%) were nonresponders. The results of the HCV genotype determined by the genotyping ELISA and by the polymerase chain reaction (PCR) assay based on genotypespecific primers were similar. The serum concentrations of HCV RNA as measured by the bDNA assay and by the competitive PCR assay correlated closely and significantly (r = 0.82, P < 0.001 1. Multiple logistic regression analysis showed that the serum concentration of HCV RNA determined by the bDNA assay, the HCV genotype determined by the genotyping ELISA, and the histology activity index (HAI) of the liver were independently associated with IFN efficacy. By using these three variables in combination, a predictive rate of 82.4% was obtained. A lower level of HCV RNA, genotype 2 and a lower HA1 score for liver histology were predictive of a favorable response to IFN. Thus, the genotyping ELISA and the bDNA assay appear to be useful for clinical management of patients receiving IFN therapy. o 1995 WiIey-Liss, Inc.
Journal of Clinical Microbiology, 2009
Assessment of the viral load in hepatitis C virus (HCV) genotype 1-infected patients is critical before, during, and after antiviral therapy. In patients achieving a rapid virological response at week 4 of treatment, the viral load at the baseline is considered a predictive criterion of a sustained virological response 24 weeks after the discontinuation of treatment. A >2-log 10 drop in the viral load at week 12 of treatment (early virological response) triggers the continuation of therapy. We organized a multicenter study (MS) for diagnostic laboratories involved in the quantification of HCV RNA. Commercial assays, including two based on real-time reverse transcription-PCR (TaqMan system), and in-house methods, were used by the 61 participants. The overall reproducibility of the commercial quantitative nucleic acid amplification techniques (qNAT) was acceptable. As the intermethod variability among commercial qNAT for HCV RNA was still present, the manufacturers of these test kits should join efforts to harmonize the means of quantification of HCV RNA. This study also shows that caution should be exercised when the baseline viral load is evaluated and when the 2-log 10 reduction after 12 weeks of therapy is interpreted. Finally, this MS confirms the higher sensitivity of the commercial qNAT based on the TaqMan system, making them the elective assays for the monitoring of therapy.