Des-gamma-carboxy prothrombin (DCP) levels reportedly correlate with histological features of hepatocellular carcinoma (HCC). We examined serum DCP as a predictor of HCC recurrence in 144 patients who underwent living donor liver transplantation. Receiver operating characteristics (ROC) analysis revealed superiority of DCP and AFP over preoperative tumor size or number for predicting recurrence. Multivariate analysis revealed tumor size >5 cm, ≥11 nodules, and DCP >400 mAU/mL as significant independent risk factors for recurrence. Incidence of microvascular invasion (62% vs. 27%, p = 0.0003) and poor differentiation (38% vs. 16%, p = 0.0087) were significantly higher for patients with DCP >400 mAU/mL than for patients with DCP ≤400 mAU/mL. In ROC analysis for patients with ≤10 nodules all ≤5 cm to predict recurrence, area under the curve was much higher for DCP than for AFP (0.84 vs. 0.69). Kyoto criteria were thus defined as ≤10 nodules all ≤5 cm, and DCP ≤400 mAU/mL. The 5-year recurrence rate for 28 patients beyond-Milan but within-Kyoto criteria was as excellent as that for 78 patients within-Milan criteria (3% vs. 7%). The preoperative DCP level offers additional information regarding histological features, and thus can greatly improve patient selection criteria when used with tumor bulk information.

Background: Optimal indications for living donor liver transplantation (LDLT) for patients with hepatocellular carcinoma (HCC) have yet not been established. The aim of the present study was to determine optimal criteria including categories outside the Milan criteria (MC) and still with a predictably good outcome. Patients and Methods: Between February 1999 and December 2007, 136 patients with HCC underwent LDLT. Based on preoperative imaging studies, 74 patients met the MC and 62 did not. Results: Overall patient survival rate at 5 years was 70%. Patients who exceeded MC but presented with ≤10 tumors and all ≤5 cm in diameter (n = 33) displayed similar 5-year recurrence rate to those within MC (7 vs. 10%). Based on the results of multivariate analysis of risk factors for recurrence, we defined new criteria as n ≤10 and all ≤5 cm and PIVKA-II ≤400 mAU/ml. The 5-year recurrence rate for the 83 patients who met the new criteria was significantly lower than for the 44 patients who exceeded them (5 vs. 61%, p < 0.0001). Similarly, patients who met the new criteria showed a significantly better 5-year survival rate (87 vs. 37%, p < 0.0001). Conclusion: The selection criteria may be safely extended up to n ≤10 and all ≤5 cm in diameter and PIVKA-II ≤400 mAU/ml with acceptable outcomes.

Living donor liver transplantation (LDLT) has evolved to represent an important surgical strategy for patients with hepatocellular carcinoma (HCC). However, due to disadvantages, including donor risks and higher rates of perioperative complications, LDLT has been considered as a second-line treatment in Japan. The present study retrospectively evaluated clinical outcomes for 93 patients with HCC who underwent LDLT at our institute, including 44 patients who exceeded Milan criteria (MC). A total of 73 patients (78%) displayed a history of previous treatment for HCC using various nontransplant methods. Median follow-up was 24 months (range, 1–76 months). At 4 years after LDLT, overall patient survival rate was 64%, with similar rates for within-MC and over-MC groups (68% vs. 59%, respectively; P = 0.6548). However, cumulative recurrence rate was significantly higher in the over-MC group than in the within-MC group (35% vs. 15%, P = 0.0190). Regarding history of conventional treatment for HCC before LDLT, patients who had received only 1–2 previous treatments showed significantly lower recurrence rates than patients with ≥3 treatments (9% vs. 37%, P = 0.0411). In conclusion, LDLT may constitute an optional treatment with a chance of cure for patients with otherwise uncontrolled disease. However, repeated nontransplant treatments for recurrent HCC prior to LDLT may increase the risk of recurrence and impair the survival advantages conferred by LDLT. Liver Transpl 12:912–919, 2006. © 2006 AASLD.

Background/purpose: The results of living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) at Kyoto University were analyzed.Methods: Between February 1999 and December 2006, 136 patients with HCC underwent LDLT. Of these, 74 patients met the Milan criteria, while 62 patients did not. Treatment for HCC had been previously performed prior to LDLT for 101 patients (74%).Results: According to the results of multivariate analysis of risk factors for recurrence among preoperative tumor variables, we have defined new Kyoto criteria as ≤10 tumors all ≤5 cm in diameter and protein induced by vitamin K absence or antagonist‐II (PIVKA‐II) ≤400 mAU/ml. The 5‐year recurrence rate was significantly lower for the 85 patients who met the Kyoto criteria than for the 45 patients who exceeded them (3 vs. 54%,p < 0.0001). Similarly, patients who met the Kyoto criteria showed a significantly better 5‐year survival rate (87%) than those who did not (36%,p < 0.0001). Survival rates did not differ between pretreated and primary groups, and recurrence rates were similarly low when limited to patients who met the Kyoto criteria.Conclusions: The proposed Kyoto criteria are expected to serve efficiently as expanded selection criteria for LDLT in patients with HCC. History of previous treatments did not affect outcomes after LDLT.

Hepatocellular carcinoma (HCC) is the third highest cause of cancer-related mortality, and liver transplantation is the ideal treatment for this disease. The Milan criteria provided the opportunity for HCC patients to undergo LT with favorable outcomes and have been the international gold standard and benchmark. With the accumulation of data, however, the Milan criteria are not regarded as too restrictive. After the implementation of the Milan criteria, many extended criteria have been proposed, which increases the limitations regarding the morphological tumor burden, and incorporates the tumor’s biological behavior using surrogate markers. The paradigm for the patient selection for LT appears to be shifting from morphologic criteria to a combination of biologic, histologic, and morphologic criteria, and to the establishment of a model for predicting post-transplant recurrence and outcomes. This review article aims to characterize the various patient selection criteria for LT, with reference to several surrogate markers for the biological behavior of HCC (e.g., AFP, PIVKA-II, NLR, 18F-FDG PET/CT, liquid biopsy), and the response to locoregional therapy. Furthermore, the allocation rules in each country and the present evidence on the role of down-staging large tumors are addressed.