Highly Sensitive HCV RNA Tests Required to Evaluate Treatment Response and Relapse Rates and to Create Individualized Treatment Strategies for Hepatitis C Patients

In order to improve individualized therapeutic strategies for patients with HCV infection, it is important to determine the most precise estimation possible of early virological response rates (EVR). The sensitive TMA test may be the best tool currently available to distinguish sustained from non-sustained responders (i.e., relapsers) at early stages of treatment.

In the current study, presented at the recent 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2007) in Boston (November 2-6, 2007), German researchers evaluated whether TMA might be a better indicator to predict long-term outcome of anti-HCV therapy in genotype 1 patients who have undetectable HCV RNA according to the branched DNA (bDNA) assay.

In this 48-week study, 433 participants were randomized to receive either 1.5 mcg/kg pegylated interferon alfa-2b (PegIntron) plus 800-1400 mg ribavirin for 48 weeks (n=225, group A) or an individualized treatment duration (n=208, group B).

In the latter group, treatment duration was calculated based on the time required to become HCV RNA negative for the first time as defined by the bDNA assay (limit of detection 615 IU/mL) multiplied by a factor 6.

HCV RNA levels were quantified weekly until week 8, then at weeks 12 and 24. The more sensitive TMA test (limit of detection 5.3 IU/mL) was also prospectively assessed for all patients who were HCV RNA negative by bDNA. The different response groups were classified according to HCV RNA levels at weeks 4 and 12.

Results

• The table shows the relevant data and refers to the relative relapse rates in group A and B at weeks 4 and 12 in relation to treatment schedule.

• There is clear evidence for a high relapse rate in patients with a positive TMA, being more pronounced within the first 12 weeks of therapy when treatment duration was shortened in the individualized treatment group.

• In contrast, patients who responded as early as week 4 as evidenced by a negative TMA test had relapse rates below 10% regardless of treatment group.

Based of these findings, the researchers concluded, "The application of the highly sensitive HCV RNA tests must be considered to be mandatory now because this new test helps to evaluate in a much more refined way treatment response as well as relapse rates and provides better clues for an individualized tailored treatment strategy."

"Our study clearly indicates that patients, even with a minimal amount of HCV RNA detected at week 12, can suffer from relapse rates greater than 50%," they continued. "These patients may indeed benefit when their treatment duration is adapted to their individual needs."

Charite, Campus Virchow Klinikum, Berlin, Germany; Medizinische Universitätsklinik, Frankfurt, Germany; Klinikum der Universität Würzburg, Würzburg, Germany; Hepatologische Schwerpunktpraxis, Berlin, Germany; Medizinische Universitätsklinik, Freiburg, Germany; Christian-Albrecht-Universität, Kiel, Germany; Universitätsklinik, Zürich, Switzerland; Medizinische Universitätsklinik, Bonn, Germany; Universitätsklinik Eppendorf, Hamburg, Germany; Essex GmbH, München, German.

11/09/07

Reference
T Berg, V Weich, G Teuber, and others. Importance of a Minimal Residual Viremia for the Relapse Prediction in HCV Type 1 Patients Receiving Standard or Individualized Treatment Duration. 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2007). Boston, MA. November 2-6, 2007. Abstract (oral) 179.