Summary:
Pawlotsky,[18] from Hôpital Henri Mondor in Paris, France, provided data on molecular testing in the setting of hepatitis B, which comprises serum HBV DNA quantification assays and assays that identify sequences in the HBV genome. HBV DNA quantification previously relied on poorly sensitive assays using hybridization or signal amplification. Although polymerase chain reaction (PCR) assays have improved sensitivity, the most frequently used tests provide limited ranges of quantification. There is currently no uniform standard for reporting HBV DNA levels, making it difficult to draw comparisons between different studies using different assays. No precise HBV DNA thresholds have been established to guide medical decision making, and different therapies are associated with different endpoints. For short-term therapies aimed at achieving HBeAg and HBsAg seroconversion, HBV DNA monitoring is of little utility; it has more value for monitoring long-term suppressive therapy. Newer real-time PCR (RT-PCR) technology allows accurate quantification over a broader range of HBV DNA levels, making it possible to both measure high HBV viral load in untreated patients and monitor the efficacy of antiviral therapy. Pawlotsky argues that this technology should be the standard for monitoring anti-HBV therapy in clinical trials and practice. Current RT-PCR assays have several limitations. In terms of technical issues, they allow for accurate quantification over a range of approximately 7-8 logs, but this is not adequate for measuring the very high HBV DNA levels in some patients. In addition, it is not clear whether current commercial RT- PCR assays measure all HBV genotypes and nucleotide polymorphisms equally. In terms of HBV sequence analysis, 3 different types of assays are used: genotyping assays, assays detecting precore and core mutations, and assays detecting resistance mutations. Genotype determination is important because it may influence the course of disease and the outcome of antiviral therapy (although genotype determination has not proven clinically useful so far).
Norah Terrault, MD, MPH:
This presentation was a nice summary of the evolution of quantitative assays for HBV DNA. Pawlotsky made a strong argument that we should move away from using copies/mL toward a standardized language of IU/mL. The conversion factor for current assays reporting in copies/mL or MEq/mL varies with the assay but for most assays, 1 IU/mL is approximately equivalent to 5 copies or MEq/mL. The need to report HBV DNA results in IU/mL was one of the strong messages of the conference, and one with which I think everyone agrees. He also recommended that we move away from quantitative assays that are relatively limited in range in favor of RT-PCR assays, which have a much more dynamic quantification range, from 10 IU/mL to 109 IU/mL. As clinicians begin to look more carefully at treatment response during the early phases of therapy, having assays that capture that full dynamic range will be important. More sensitive assays will be also useful for analyzing the kinetics of the viral response and long-term outcomes. To date, clinical trials have used different assays with different cutoffs, which has made it very difficult to make comparisons across studies. Having a uniform way of reporting HBV DNA levels across studies will make it easier to interpret data from different clinical trials. As Pawlotsky noted, one limitation of the current quantitative assays, particularly the new RT-PCR assays, is that there are few data on assay performance across HBV genotypes. This is an area that requires further study.
Adrian M. Di Bisceglie, MD, FACP:
Pawlotsky recommended that the goal of therapy should be to reduce HBV DNA to below 50 IU/mL (equivalent to approximately 300 copies/mL), emphasizing that we need to discontinue the use of copies/mL and universally report in IUs.
发表于 2006-10-22 01:45
