Volume 41, Issue 6, Pages 935-942 (December 2004) Evaluation of a panel of non-invasive serum markers to differentiate mild from moderate-to-advanced liver fibrosis in chronic hepatitis C patients  Keyur Patel, Stuart C. Gordon, Ira Jacobson, Christophe Hézode, Esther Oh, Katie M. Smith, Jean-Michel Pawlotsky, John G. McHutchison  Journal of Hepatology  Volume 41, Issue 6, Pages 935-942 (December 2004) DOI: 10.1016/j.jhep.2004.08.008 Copyright © 2004 European Association for the Study of the Liver Terms and Conditions

Fig. 1 Box plots of the serodiagnostic marker panel for hyaluronic acid, TIMP-1 and alpha2-macroglobulin in the estimation cohort of 294 patients. The box represents the 25th and 75th percentiles and the median is shown by a horizontal line. The whiskers represent the upper and lower range of values for each marker. The differences between the F0–F1 and F2–F4 groups for each of the three markers was significant (P<0.0001 by unpaired t-test). Journal of Hepatology 2004 41, 935-942DOI: (10.1016/j.jhep.2004.08.008) Copyright © 2004 European Association for the Study of the Liver Terms and Conditions

Fig. 2 Receiver operating characteristic curves for modeling based on the presence of METAVIR stage F2–F4 for the three markers individually and as a combined algorithm in the estimation cohort of 294 patients. Area under ROC curve (AUC) and p values compared to regression index were: combined markers (0.831; CI: 0.785–0.876), hyaluronic acid (HA) (0.794; CI: 0.743–0.845, P=0.07), TIMP-1 (0.800; CI: 0.751–0.849; P=0.07) and alpha2-macroglobulin (A2M) (0.727; CI: 0.669–0.785; P=<0.0001). Journal of Hepatology 2004 41, 935-942DOI: (10.1016/j.jhep.2004.08.008) Copyright © 2004 European Association for the Study of the Liver Terms and Conditions

Fig. 3 Regression index scores for METAVIR stages F0–F4 in the estimation cohort (n=294) and healthy blood donor controls (n=15). The box represents the 25th and 75th percentiles and the median is shown by a horizontal line. The whiskers represent the upper and lower range of values for each marker. Except where indicated, all differences between groups were significant (P<0.001, Dunns Multiple Comparison test). Journal of Hepatology 2004 41, 935-942DOI: (10.1016/j.jhep.2004.08.008) Copyright © 2004 European Association for the Study of the Liver Terms and Conditions

Fig. 4 Performance characteristics for the estimation cohort (n=294) indicates a gradual decline in the predictive value of a positive test (PPV) with decreasing prevalence rates for METAVIR stage F2–F4 fibrosis. At a lower prevalence for significant fibrosis there is an increase in the predictive value of a negative test (NPV), although accuracy remains essentially unchanged. Journal of Hepatology 2004 41, 935-942DOI: (10.1016/j.jhep.2004.08.008) Copyright © 2004 European Association for the Study of the Liver Terms and Conditions

Fig. 5 Distribution of regression index scores across METAVIR fibrosis stages in the estimation cohort (n=294; prevalence of F2–F4=50.7%) which demonstrates higher negative predictive values with decreasing index scores and higher positive predictive values with increasing index scores. Journal of Hepatology 2004 41, 935-942DOI: (10.1016/j.jhep.2004.08.008) Copyright © 2004 European Association for the Study of the Liver Terms and Conditions