ABSTRACT: OBJECTIVE:The objective was to develop a multiparametric CT algorithm to stage liver fibrosis in patients with chronic hepatitis C virus (HCV) infection. MATERIALS AND METHODS:Abdominal CT and laboratory measures in 469 patients with HCV (340 men and 129 women; mean age, 50.1 years) were compared against the histopathologic Metavir fibrosis reference standard (F0, n = 49 patients; F1, n = 69 patients; F2, n = 102 patients; F3, n = 76 patients; F4, n = 173 patients). From the initial candidate pool, nine CT and two laboratory measures were included in the final assessment (CT-based features: hepatosplenic volumetrics, texture features, liver surface nodularity [LSN] score, and linear CT measurements; laboratory-based measures: Fibrosis-4 [FIB-4] score and aspartate transaminase-to-platelets ratio index [APRI]). Univariate logistic regression and multivariate logistic regression were performed with ROC analysis, proportional odds modeling, and probabilities. RESULTS:ROC AUC values for the model combining all 11 parameters for discriminating significant fibrosis (? F2), advanced fibrosis (? F3), and cirrhosis (F4) were 0.928, 0.956, and 0.972, respectively. For all nine CT-based parameters, these values were 0.905, 0.936, and 0.972, respectively. Using more simplified panels of two, three, or four parameters yielded good diagnostic performance; for example, a two-parameter model combining only LSN score with FIB-4 score had ROC AUC values of 0.886, 0.915, and 0.932, for significant fibrosis, advanced fibrosis, and cirrhosis. The LSN score performed best in the univariate analysis. CONCLUSION:Multiparametric CT assessment of HCV-related liver fibrosis further improves performance over the performance of individual parameters. An abbreviated panel of LSN score and FIB-4 score approached the diagnostic performance of more exhaustive panels. Results of the abbreviated panel compare favorably with elastography, but this approach has the advantage of retrospective assessment using preexisting data without planning.