Validation of novel Japanese indication criteria and biomarkers among living donor liver transplantation recipients with hepatocellular carcinoma - a single center retrospective study

Abstract

Aim: To validate a novel Japanese indication criteria for liver transplantation (LT) for hepatocellular carcinoma (HCC), i.e., the 5-5-500 criteria (nodule size ≤ 5 cm in diameter, nodule number ≤ 5, and alfa-fetoprotein (AFP) value ≤ 500 ng/mL) and the Japanese double eligibility criteria (DEC) (patients meeting the Milan or the 5-5-500 criteria) in the University of Tokyo cohort. The usefulness of biomarkers in predicting the recurrence of HCC was also verified. Methods: The overall survival and recurrence rates of patients meeting the Milan, 5-5-500, and the Japanese DEC were compared among 153 patients who underwent living donor LT (LDLT) between 1996 and 2019. A receiveroperating characteristics curve analysis was conducted to evaluate the usefulness of AFP, lens culinaris agglutininreactive fraction of AFP, des-gamma-carboxy prothrombin, neutrophil-lymphocyte ratio, and the plateletlymphocyte ratio to detect recurrence. Results: The 5-year recurrence rate for all patients, those meeting the Japanese DEC, 5-5-500 criteria, and the Milan criteria was 10.9%, 9.2%, 7.4%, and 7.6%, respectively. Compared with the conventional Milan criteria, the 5-5-500 criteria and the Japanese DEC could increase the number of eligible LDLT candidates by 6.1% and 11.4%. Among five biomarkers, the area under the curve value of AFP was the highest (0.852).

Current Therapeutic Strategies for Hepatocellular Carcinoma in Japan

“…2 ) recommend transplantation if the tumor burden is small or best supportive care if the tumor burden is large. For liver transplantation, the 5-5-500 criteria, which is defined as tumor status up to 5 nodules with a maximum diameter of 5 cm and AFP value of 500 ng/mL or less were approved by insurance coverage in April 2020 [ 96 , 97 ] in addition to the Milan criteria [ 98 ] and included in the 2021 edition of the JSH Clinical Practice Guidelines for HCC ( Fig. 2 ) [ 23 ].…”

Liver transplantation for hepatocellular carcinoma: Historical evolution of transplantation criteria

“…In fact, the majority of the extended criteria that have been discussed in the following section were defined by centers that perform LDLT at a high volume (Table 1 )[ 21 - 45 ]. As the new biomarkers have been incorporated to use during the evaluation of the patients with HCC, it was realized that tumor biology was more important in determining the prognosis of patients with HCC following LT. Kyoto criteria was one of the first to incorporate morphologic characteristics of the tumor with laboratory parameters such as Des-carboxyprothrombin.…”

“…In 2016 the same group defined the extended Toronto criteria, which included absence of cancer related symptoms to the criteria[ 35 ]. In 2019 and 2020, Shimamura et al [ 38 ] and Ichida et al [ 45 ] defined the 5-5-500 criteria, which included tumors with a diameter ≤ 5 cm, number of tumor nodules ≤ 5 and alpha fetoprotein (AFP) ≤ 500 ng/mL.…”