The Japanese 5-5-500 Rule Predicts Prognosis of Hepatocellular Carcinoma After Hepatic Resection

The 5-5-500 rule has been proposed to increase the candidates of liver transplantation for patients with hepatocellular carcinoma with reasonable recurrence rates. However, the clinical significance of the 5-5-500 rule in patients who underwent hepatic resection for hepatocellular carcinoma has not been fully investigated.

The study comprised 206 patients who had undergone primary hepatic resection for hepatocellular carcinoma between 2008 and 2018. We retrospectively investigated prognostic significance of the 5-5-500 rule and disease-free, as well as overall, survival and further prognostic stratification using inflammatory-based biomarkers.

132 patients (64%) were classified within the 5-5-500 rule, while 74 patients (36%) were classified outside the 5-5-500 rule. Among the patients outside the 5-5-500 rule, 62 patients had tumors greater than 5 cm, and 23 patients showed serum AFP levels greater than 500 ng/ml. In the multivariate analysis, being female (p<0.01), HBs-Ag positive (p<0.01), having an ICG_R15 ≥15% (p=0.03), and being outside the 5-5-500 rule (p=0.01) were independent and significant predictors of disease-free survival, while being HBs-Ag positive (p=0.04), having poor tumor differentiation (p=0.03), and residing outside the 5-5-500 rule (p=0.01) were independent and negative predictors of overall survival. Elevated CRP-to-albumin ratio was associated with poor overall survival in the patients outside the 5-5-500 rule, but not in patients within the 5-5-500 rule (p=0.17).

The 5-5-500 rule can be a prognostic factor in patients with hepatocellular carcinoma after hepatic resection. CRP-to-albumin ratio might be useful to stratify the outcomes in patients outside the 5-5-500 rule.