In the 521 liver cirrhosis patients with triple follow‐up, using a fixed cutoff of 20 ng/mL for AFP and 0.5 output units for the Doylestown algorithm resulted in a 7.4% increased biomarker performance at the closest time point to HCC diagnosis (0–6 month prior), a 21% increase 6–12 months before diagnosis, and a 13% increase 12–18 months before diagnosis. This evidence concerns the gene AFP and cirrhosis of liver.