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
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.
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).
week 8 model was not inferior for predicting SVR compared
with models that included a week 12 HCV RNA measurement
(PA index 0.831).
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
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.
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).