Background  Non-invasive liver fibrosis scores such as Hepascore (HS) have been proposed as an alternative to liver biopsy in hepatitis C virus (HCV)-infected patients.

Aim  To validate HS as an alternative to liver biopsy and Fibrotest (FT) and propose five optimized combination algorithms to improve diagnostic accuracy.

Methods  The cohort included 467 patients with HCV. There were 274/467 (59%) men, and mean age was 47 ± 12 years.

Results  Hepascore area under ROC curves (AUC) for ≥F2, F3F4 and F4 diagnosis were 0.82, 0.84 and 0.90 respectively, in the same range as FT. HS and FT were concordant in 387/467 (82%) for fibrosis staging. Among these patients, 342/387 (88%) were concordant with liver biopsy. AUCs of aspartate aminotransferase (AST) to Platelets Ratio Index (APRI) and Forns for ≥F2 were 0.76 and 0.73 (0.65–0.79) respectively. The algorithm combining APRI and HS had the highest rate of avoided liver biopsies (45%) with a high diagnostic accuracy (91%).

Conclusions  Hepascore is an accurate non-invasive marker for ≥F2 and F4 diagnosis in HCV patients. In a pragmatic approach, a stepwise optimized algorithm combining APRI and FT or HS considerably increases diagnostic accuracy and avoided liver biopsies.