Expanded living-donor liver transplantation criteria for patients with hepatocellular carcinoma based on the Japanese nationwide survey: the 5-5-500 rule - a retrospective study

Transpl Int. 2019 Apr;32(4):356-368. doi: 10.1111/tri.13391. Epub 2019 Jan 18.


Expansion of the liver transplantation indication criteria for patients with hepatocellular carcinoma (HCC) has long been debated. Here we propose new, expanded living-donor liver transplantation (LDLT) criteria for HCC patients based on a retrospective data analysis of the Japanese nationwide survey. A total of 965 HCC patients undergoing LDLT were included, 301 (31%) of whom were beyond the Milan criteria. Here, we applied the Greenwood formula to investigate new criteria enabling the maximal enrollment of candidates while securing a 5-year recurrence rate (95% upper confidence limit) below 10% by examining various combinations of tumor numbers and serum alpha-fetoprotein values, and maintaining the maximal nodule diameter at 5 cm. Finally, new expanded criteria for LDLT candidates with HCC, the 5-5-500 rule (nodule size ≤5 cm in diameter, nodule number ≤5, and alfa-fetoprotein value ≤500 ng/ml), were established as a new regulation with a 95% confidence interval of a 5-year recurrence rate of 7.3% (5.2-9.3) and a 19% increase in the number of eligible patients. In addition, the 5-5-500 rule could identify patients at high risk of recurrence, among those within and beyond the Milan criteria. In conclusion, the new criteria - the 5-5-500 rule - might provide rational expansion for LDLT candidates with HCC.

Keywords: hepatocellular carcinoma; living donor liver transplantation.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / surgery*
  • Child
  • Female
  • Humans
  • Liver Neoplasms / blood
  • Liver Neoplasms / mortality
  • Liver Neoplasms / surgery*
  • Liver Transplantation / methods*
  • Living Donors*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Retrospective Studies
  • Young Adult
  • alpha-Fetoproteins / analysis


  • alpha-Fetoproteins