Quantification and genotyping of serum HCV-RNA in patients with chronic hepatitis C undergoing interferon treatment

Gerken, Guido; Knolle, Percy A.; Jakobs, Simone; Büschenfelde, K H Meyer zum

doi:10.1007/s007050050092

Cited by 11 publications

(10 citation statements)

References 12 publications

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“…This model may provide a clinically useful tool for the estimation of the period of time in which patients are likely to have a serum viral load correlated with likely response to antiviral therapy. [35][36][37] However, a greater understanding of the natural history of chronic HCV infection and the correlations between viral load, histological activity indices, age, duration of disease, and gender may lead to more refined models for the prediction of viral load fluctuations over time. In summary, this opportunity to control for the variables that can influence the natural history of hepatitis C infection has helped illuminate some clinically relevant characteristics of this persistent viral infection such as the magnitude of viral load modulation over time and the rate of change of viral load in HCV 1b infection and its relationship to age at infection.…”

Section: Discussionmentioning

confidence: 99%

Natural fluctuations of hepatitis C viral load in a homogeneous patient population: A prospective study

et al. 2000

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Hepatitis C virus (HCV) infection is the main cause of parenteral non-A, non-B hepatitis. 1-5 HCV consists of a heterogeneous mix of isolates defined by genotype, each of which is further classified into subtypes. A number of factors have been identified as important in predicting the outcome of disease progression. These include age at infection, viral type/subtype, viral load, quasispecies, and mode of infection. [6][7][8][9][10] Clinical heterogeneity in disease progression may reflect either viral heterogeneity or variations in host response. However, the fluctuations in viral load during the natural history of hepatitis C infection are poorly understood. The purpose of the present study was to determine if viral load remains at a steady state or is in dynamic flux during the course of an HCV infection. To avoid heterogeneity of risk factors and confounding variables in viral type/subtype, we studied a unique cohort of individuals all infected by anti-D/ blood product from a single source of HCV 1b. The sole source of the infectious agent was identified as HCV 1b-contaminated anti-D immunoglobulin. The contaminating HCV 1b was derived from a single donor. [11][12][13] The patients were of similar ethnogeographic background and had an absence of other risk factors for liver disease.Serum HCV RNA can be quantitated by a range of different technologies (reverse transcription-polymerase chain reaction [RT-PCR], RT-PCR coupled to different signal amplification systems such as colorimetric assays, and the branched chain technology). [14][15][16][17][18][19][20] The level of sensitivity achieved by the more recent versions of these technologies has improved qualitative assessment of HCV serum status. Clinically relevant sensitivities of 100 viral genomes per mL of serum are now readily achievable.The work reported here used the Roche Monitor system for amplification of the HCV. The high degree of reproducible quantification of viral load and a uniform linear range of amplification between the different versions of the Roche HCV Monitor assays for HCV of genotype 1b provide a means in which quantifications over several generations of assays are suitable for longitudinal studies. In addition, amplification of HCV genotype 1b by the Monitor system does not suffer from the reported difficulties associated with other genotypes. 21

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Section: Discussionmentioning

confidence: 99%

Natural fluctuations of hepatitis C viral load in a homogeneous patient population: A prospective study

et al. 2000

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“…HCV RNA in serum was qualitatively detected by RT-PCR (Amplicor) [3]. In addition, HCV RNA concentration in serum was determined by RT-PCR (HCV Monitor Assay, Hofmann-La Roche, Grenzach-Whylen, Germany) [4]. The assays were performed according to the manufacturer's instructions.…”

Section: Detection Of Hcv Rna In Serummentioning

confidence: 99%

Viral and host factors in the prediction of response to interferon‐α therapy in chronic hepatitis C after long‐term follow‐up

Knolle

Kremp

Hawranek

et al. 1998

Journal of Viral Hepatitis

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Acute infection with hepatitis C virus (HCV) develops into a chronic hepatitis in about 50-70% of patients. Treatment of these patients with interferon-alpha (IFN-alpha) results in a sustained long-term response in only 15-20% but causes numerous unwanted side-effects in a higher percentage of patients. The aim of our study was to define host or viral parameters that would allow identification of responders and non-responders to IFN-alpha prior to the onset of treatment. We studied a group of 87 patients suffering from chronic hepatitis C who were treated with IFN-alpha. After long-term follow-up, 18 patients (21%) showed a sustained response to IFN-alpha therapy (normalization of serum transaminases and loss of viral RNA from serum) for up to 7 years after therapy had ceased. By univariate and multivariate analyses, no host factors were found to be predictive of response to therapy. Neither the degree of inflammation or fibrosis in liver biopsy samples obtained before treatment nor immunogenetic factors (major histocompatibility complex II haplotype and tumour necrosis factor-alpha promoter polymorphism) were associated with response to therapy. In contrast, viral parameters showed a strong association with response to therapy. HCV genotype 3 was found significantly more frequently in responders (P = 0.034), and mean HCV RNA concentration was lower in responders (3.1 x 10(4)) than in non-responders (2.5 x 10(5)) (P = 0.01). By multivariate analysis, both HCV genotype and HCV RNA concentration were independent predictors of response to therapy. However, exact prediction of response to treatment for an individual patient was not possible on the basis of pretreatment viral RNA concentration or viral genotype. The best association with response to therapy was found to be clearance of HCV RNA from serum 3 months after the start of treatment (32 of 34 partial and sustained responders vs 0 of 53 non-responders; P = 0.001). In conclusion, determination of pretreatment viral factors, but not host factors, was significantly correlated with treatment response but did not give an accurate prediction for patients, whereas clearance of HCV RNA from serum after 3 months of therapy was predictive of response to therapy.

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“…Several reports have demonstrated the correlation of HCV viral kinetics during interferon therapy with genotypes and their influence on virological response [7,12,13]. Studies have suggested that combination therapy reduces the relapse of HCV infection, as compared with interferon alone, thereby increasing the possibility of sustained virological response [8].…”

Section: Discussionmentioning

confidence: 99%

Response of Combination Therapy on Viral Load and Disease Severity in Chronic Hepatitis C

et al. 2007

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Influence of genotypes on viral kinetics and disease severity in chronic hepatitis C (CH-C) patients has been implicated, but requires further investigation. The 41 HCV patients were genotyped by restriction fragment length polymorphism and included for 48 weeks of combination therapy on the basis of clinical (alanine amino transferase > or =60 IU/l) and histological features (histological activity index > or =3). A significant number (30/41) of patients (6/9 of genotype 1, 23/30 of genotype 3 and 1/2 of mixed genotype) attain sustained virological response despite high viral load at baseline. More aggressive treatment was required in genotype 1 than in genotype 3 due to slow response rate. Significant (P < 0.05) difference in the viral load of sustained virological responder and non-responder (NR) was observed after 12 weeks of therapy. Severe course of liver disease was observed in 81.81% (9/11) of NR patients at baseline. Data indicate that genotype 1 was a slow responder compared to genotype 3 on combination therapy. Response to combination therapy was almost independent of baseline viral load. However, a positive correlation of viral load with disease severity was observed. The viral kinetics at 12 weeks is an important tool for determination of virological response.

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Quantification and genotyping of serum HCV-RNA in patients with chronic hepatitis C undergoing interferon treatment

Cited by 11 publications

References 12 publications

Natural fluctuations of hepatitis C viral load in a homogeneous patient population: A prospective study

Natural fluctuations of hepatitis C viral load in a homogeneous patient population: A prospective study

Viral and host factors in the prediction of response to interferon‐α therapy in chronic hepatitis C after long‐term follow‐up

Response of Combination Therapy on Viral Load and Disease Severity in Chronic Hepatitis C

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