Differences in the impact of prognostic factors for hepatocellular carcinoma over time

The aim of the present study was to evaluate the prognostic significance of serum markers that reflect tumor progression, liver function, or liver fibrosis in patients with hepatocellular carcinoma (HCC), focusing on how their impact changes over time after diagnosis. Alpha‐fetoprotein (AFP), des‐gamma‐carboxy prothrombin (DCP), albumin‐bilirubin (ALBI) score, aspartate aminotransferase to platelet ratio index (APRI), and FIB‐4 index were measured at the time of initial non‐recurrent HCC diagnosis in 1669 patients between 1997 and 2016. Survival rates after diagnosis were compared after stratifying patients by these markers. Time‐dependent receiver‐operating characteristics (ROC) analysis was carried out to assess how these markers predict patient survival or death. Serum AFP and DCP levels, ALBI score, and APRI and FIB‐4 index were strongly correlated with HCC progression, liver function, and degree of liver fibrosis, respectively. Survival rates after diagnosis were significantly different when patients were stratified by these markers. In the time‐dependent ROC analysis, AFP and DCP had a high prognostic impact within 3 years of diagnosis but the impact decreased thereafter. In contrast, APRI and FIB‐4 index had higher prognostic impact 10 years after diagnosis. ALBI score had a high prognostic impact throughout the study period. Time‐dependent ROC analysis clearly showed changes in the prognostic importance of serum markers based on the duration after diagnosis. Whereas the prognostic impact of tumor progression markers was strong in the short term, liver fibrosis markers had higher prognostic impact long after diagnosis. Liver function had constant prognostic impact on patient survival after diagnosis.