Usefulness of the Kyoto criteria as selection criteria for living donor liver transplantation for hepatocellular carcinoma

With the advent of the Milan criteria (MC) for patient selection, deceased donor liver transplantation (DDLT) has been performed a large number of times, with excellent results, in Western transplantation centers for patients with hepatocellular carcinoma (HCC). In Eastern countries, the high incidence of HCC and the critical shortage of deceased organ donation have led to the rapid development of living donor liver transplantation (LDLT) for HCC patients. In both Western and Eastern transplantation centers, some expanded criteria based on tumor morphology have been proposed because the MC may be too restrictive. However, expansion of the criteria naturally carries a risk of increased posttransplant recurrence. Therefore, expanded criteria can be justified only if the criteria show acceptably low recurrence rates. In a retrospective analysis of 136 HCC patients who underwent LDLT at our institute between February 1999 and December 2006, we recently proposed new selection criteria (the Kyoto criteria) for LDLT in patients with HCC using a combination of the tumor number, the tumor size (based on pretransplant imaging using contrast-enhanced multidetector computed tomography), and a tumor marker: a tumor number 10, all tumors 5 cm in size, and a protein induced by vitamin K absence or antagonist-II (PIVKA-II) level 400 mAU/mL. The Kyoto criteria are a combination of 3 independent significant risk factors of recurrence, including a specific tumor marker of HCC. Patients with a PIVKA-II level > 400 mAU/mL showed a significantly higher incidence of positive microvascular invasion and a markedly higher incidence of poorly differentiated grade in comparison with patients with a PIVKA-II level 400 mAU/mL. Consequently, the Kyoto criteria could effectively exclude patients with biologically aggressive tumors before liver transplantation (LT) and promote an extremely low recurrence rate. However, the superiority of the Kyoto criteria to other expanded criteria is unclear. We therefore compared the overall survival and recurrence rates of the 136 HCC patients stratified by 6 representative selection criteria, including ours, to examine the usefulness of the Kyoto criteria. Table 1 shows the overall survival rates and recurrence rates after LT and the inclusion rates stratified by the respective criteria: the MC (a single tumor 5 cm in size or 3 or fewer tumors, each 3 cm in size), the Tokyo criteria (tumor number 5 and all tumors 5 cm in size), the Kyushu criteria (all tumors < 5 cm in size or PIVKA-II < 300 mAU/mL), the Up to 7 criteria (sum of the size of the largest tumor in centimeters and the number of tumors 7), and the University of California San Francisco criteria (a solitary tumor 6.5 cm in size or 3 or fewer nodules with the largest lesion 4.5 cm in size and a total tumor diameter 8 cm). The 1-, 3-, and 5-year overall survival rates and recurrence rates of patients who met the Kyoto criteria were superior to those of patients treated under other criteria. Similarly, those rates for patients beyond the Kyoto criteria were the worst in comparison with those of patients treated under other criteria, except for those of patients treated under the Kyushu criteria. In fact, the inclusion rate under the Kyoto criteria was 65.7%, whereas that under the Kyushu criteria was 95.6% (nearly 100%). In other words, the Kyoto criteria could most significantly stratify patient survival as well as recurrence rates with an appropriate inclusion rate. Because of the risks to the live donor as well as the higher perioperative morbidity and mortality of the recipient in LT in comparison with those in other treatment modalities for HCC, at least an 80% overall survival rate at 5 years after LDLT would be desirable. The findings of an 85.2% 5-year survival rate and a 2.9% 5-year recurrence rate in patients who met the Kyoto criteria demonstrate that the Kyoto criteria are excellent and acceptable new expanded criteria for LDLT for HCC. To investigate the validity of the expanded criteria in comparison with the MC, the prognosis of HCC patients beyond the MC should also be examined.