All patients with cirrhosis

• Non-cirrhotic chronic hepatitis B patients meeting any of the following criteria: positive family history for HCC, intermediate-high aMAP and/or (m)PAGE-B score (if non-Caucasian)
• Non-cirrhotic chronic hepatitis C patients (with or without SVR) with a history of F3 fibrosis (based on histology or liver stiffness assessment)
• Non-cirrhotic NASH patients with a history of F3 fibrosis (based on histology or liver stiffness assessment)

In order to calculate the GAAD score an in-vitro diagnostic is used. The Elecsys GAAD assay by Roche Diagnostics is used to assess the GAAD score using on blood samples collected from patients during regular outpatient clinic visits. The Elecsys GAAD test combines the results of the Elecsys PIVKA-II and Elecsys AFP assays with gender and age (the GAAD score is calculated with PIVKA-II, AFP, gender and age).

The diagnostic value of the GAAD score for HCC will be expressed using sensitivity, specificity, positive and negative predictive values, both overall and for the subgroup of early stage (BCLC 0-A) HCC. The GAAD scores will be measured and documented separately for each visit. The diagnostic value of the GAAD score will be assessed for HCC diagnosed at the index visit (ie the visit at which the GAAD score was determined) and for HCC diagnosed on imaging performed at 6 months after the index visit.

Change in GAAD score over time in relation to confounding factors will be analysed using pairwise comparisons and linear regression. The following confounding factors will be analysed: age in years, gender, ALT, creatinine umol/L and bilirubin U/L. The proportion of patients with a GAAD score above the cut-off will be shown using descriptive statistics. The association between the occurrence of HCC in relation to the change in GAAD score, (from below to above the cut-off score) will be expressed using sensitivity, specificity, positive and negative predictive values as described above.