Assessment of HCV
RNA at Week 4 and Week 12 Optimizes Prediction of Treatment Outcomes in HCV Patients
Treated with Pegylated Interferon Alfa-2b (PegIntron) plus Ribavirin HCV
RNA level (viral load) prior to treatment
is an important predictor of treatment outcomes in patients with chronic
hepatitis C. Previously, Stefan Zeuzem and colleagues (AASLD 2006) proposed
400,000 IU/ml (assessed with the COBAS TaQMan HCV assay) as the optimal cut-off
to best discriminate low and high viral load, based on the probability of achieving
sustained virological response
(SVR) in patients treated with pegylated
interferon alfa-2b (PegIntron) plus ribavirin. In
the current study, presented at the 58th Annual Meeting
of the American Association for the Study of Liver Diseases (AASLD) in Boston,
MA (November 2-6, 2007), researchers aimed to analyze the positive predictive
value (PPV) of this cut-off value at baseline, the PPV of rapid virological response
(RVR) at week 4, and the negative predictive value (NPV) of failure to
achieve early virological response (EVR) at week 12 (non-EVR12), in patients treated
with PegIntron
plus ribavirin. A
total of 408 consecutive patients (221 treatment-naive; 187 non-naive) received
treatment with 1.5 mcg/kg/week pegylated interferon alfa-2b plus 800-1200 mg/day
ribavirin according to weight. Patients with HCV genotypes 1, 4, or 5 and prior
non-responders were treated for 48 weeks; treatment-naive patients with genotypes
2 or 3 were treated 24 weeks. Serum
HCV RNA was measured at baseline, week 4, week 12, end of treatment, and 6 months
after the end of treatment using the quantitative Versant HCV 3.0 Assay (bDNA)
(Siemens Medical Solution Diagnostics). Samples below the limit of quantification
were tested with the Versant HCV RNA Qualitative Assay (TMA) (Siemens Medical
Solution Diagnostic). SVR was defined as undetectable serum HCV RNA by TMA at
end of 6 months post-treatment follow-up. •
At treatment
initiation PPV was defined with a cut-off set up at < 400,103 IU/mL.
•
At week
4, the PPV was defined as TMA undetectable or >2 log drop from baseline
viral load.
•
At
week 12, the NPV was defined as TMA detectable or < 2 log drop from baseline
viral load.
•
The
overall SVR rate was 46% (53% in treatment-naive patients and 38% in non-naive
patients).
| PPV | PPV | PPV | NPV | NPV | Baseline | Week
4 | Week
4 | Week
12 | Week
12 | Viral
load | <40,000
IU/ml | TMA
negative | >
2 log drop | TMA
positive | <
2 log drop | All
patients | 62% | 97% | 70% | 87% | 98%
| Naive | 63% | 96% | 78% | 83% | 100% | Non-responder
| 27% | 100% | 50% | 90% | 96% | Relapser | 76% | 100% | 70% | 76% | 100% |
Conclusion
Based on
these findings, the investigators concluded, "Undetectable HCV RNA at week
4 (RVR) when assessed with a sensitive assay (TMA) is more accurate (96%-100%)
than baseline cut-off (<400,103 IU/mL) to predict SVR both in naive
and in experienced patients." The
also noted, "The absence of EVR at week 12 (less than 2 log reduction of
HCV RNA) is a strong predictor (96%-100%) of non response to therapy independently
of the patient's pretreatment status." Université
paris VII, Hopital Beaujon, Clichy, France; 2Service d'Hépatologie, Hopital
Beaujon, Clichy, France. 11/20/07 Reference
M Martinot-Peignoux,
S Maylin, M P Ripault, and others. Assessment of both Virological Response at
Week 4 and at Week 12 Optimizes Prediction of Treatment Outcome in Patients with
Chronic Hepatitis C Treated with Peginterferon Alfa-2bg plus Ribavirin. 58th Annual
Meeting of the American Association for the Study of Liver Diseases. Boston, MA.
November 2-6, 2007. Abstract 304. 
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