Response at Week 8 Accurately Predicts Sustained Response to Pegylated Interferon plus Ribavirin for Hepatitis C

SUMMARY: Virological response to interferon-based therapy at week 8 is as likely to accurately predict which chronic hepatitis C patients will go on achieve sustained response as the usual 12-week stopping algorithm, according to a study published in the May 2010 Journal of Viral Hepatitis. Using this earlier cut-off for treatment discontinuation could spare patients the side effects and cost of additional futile therapy.

By Liz Highleyman

Early virological response (EVR) -- an HCV viral load decline of at least 2 logs 12 weeks after starting pegylated interferon plus ribavirin -- is typically used as a "stopping rule" to predict which hepatitis C patients are likely to achieve sustained virological response (SVR) as measured 24 weeks after completing treatment. Individuals who have not demonstrated significant viral load decline by week 12 are unlikely to do so later, and are often advised to discontinue therapy at this time.

E. Lukasiewicz and colleagues with the international DITTO-HCV Study Group performed an analysis to assess whether treatment response before week 12 would also accurately predict sustained response, thereby sparing patients additional weeks of futile therapy.

The investigators used a technique called longitudinal discriminant analysis to build and validate mathematical models that included patient characteristics and HCV RNA measurements at 4, 8, or 12 weeks of treatment. They calculated a partial area under the curve (PA) index for each time point, comparing their accuracy of prediction in the range of high negative predictive values.

Results

• Failure to achieve sustained virological response was best predicted before week 12 by a single HCV viral load measurement at week 8, together with patient sex, age, and body mass index (PA index 0.857).
• The week 8 model was not inferior for predicting SVR compared with models that included a week 12 HCV RNA measurement (PA index 0.831).
• The best model using only viral load measurements up to week 4, however, was inferior to the week 8 model (PA index 0.796).

These results, the study authors concluded, "indicate that lack of sustained viral response is best predicted after 8 weeks of treatment and that waiting until 12 weeks does not improve the prediction."

Investigator affiliations: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel; Faculty of Industrial Engineering and Management, Technion, Technion City, Haifa, Israel; Gertner Institute for Epidemiology, Sheba Medical Center, Tel Hashomer, Israel; Department of Virology, INSERM U635, Henri Mondor Hospital, University of Paris XII, Creteil, France; Department of Hepatology and Gastroenterology, University Hospital Rotterdam Dijkzigt, Rotterdam, Netherlands; Division of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy; Universitätsklinikum des Saarlandes, Homburg, Saarland, Germany.

7/13/10

Reference

E Lukasiewicz, M Gorfine, LS Freedman, and others (DITTO-HCV Study Group). Prediction of nonSVR to therapy with pegylated interferon-alpha-2a and ribavirin in chronic hepatitis C genotype 1 patients after 4, 8 and 12 weeks of treatment. Journal of Viral Hepatitis 7(5): 345-351 (Abstract). May 2010.

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