Hepatocellular carcinoma – time to take the ticket

Table 1 Modified UCSF down-staging criteria

Inclusion criteria

a) 1 lesion > 5 cm and ≤ 8 cm

b) 2 or 3 lesions, at least one > 3 cm but ≤ 5 cm + the total tumor diameter ≤ 8 cm

c) 4 or 5 lesions, all ≤ 3 cm + the total tumor diameter ≤ 8 cm

d) No vascular invasion on imaging

Criteria for successful down-staging

Tumor size and number need to satisfy the UNOS T2 criteria

Complete tumor necrosis without contrast enhancement to suggest residual tumor, equivalent to obliteration of the tumor irrespective of the tumor size

Additional guidelines

1) A minimum observation period of 3 mo after down-staging is required before deceased donor liver transplantation, and if imaging studies meet the above-mentioned criteria for successful down-staging

2) Patients can undergo live donor liver transplantation at 3 mo after down-staging, and if imaging studies satisfy the UCSF criteria

3) Those with acute hepatic decompensation after the down-staging procedure are not eligible for liver transplantation unless they satisfy the abovementioned criteria

Table 2 Extended criteria currently in use

Extended criteria
UCSF[28]	Single tumor ≤ 6.5 cm in diameter or no more than 3 lesions ≤ 4.5 cm in diameter, and total tumor diameter ≤ 8 cm
Asan criteria[29]	≤ 6 tumors, all ≤ 5 cm in diameter, and no gross vascular invasion
Valencia criteria[30]	1-3 tumors ≤ 5 cm and cumulative tumor burden ≤ 10 cm
Up-to-7 criteria[14]	Sum of the sizes of the largest tumor (in cm) and the number of tumors ≤ 7
CUN criteria[31]	Single tumor ≤ 6 cm or up to 3 nodules ≤ 5 cm
Mount-Sinai[32]	Any number of lesions, each is 5-7 cm in diameter
Edmonton[33]	Number of single tumors ≤ 7, tumor ≤ 5 cm in diameter
Dallas[34]	Single tumor diameter ≤ 6 cm or 2-4 tumors each ≤ 5 cm in diameter
Tokyo[35]	≤ 5 tumors not exceeding 5 cm in diameter
Shanghai[36]	Single tumor ≤ 9 cm in diameter or no more than 3 nodules with the largest nodule ≤ 5 cm in diameter, overall tumor diameter ≤ 9 cm without extrahepatic metastasis, lymph node or macrovascular invasion

Table 3 Criteria including tumor biomarkers

Biomarker criteria
TTV/AFP[18]	Total tumor volume ≤ 115 cm3 and AFP ≤ 400 ng/mL
AFP-TTD[37]	Total tumor diameter ≤ 8 cm and AFP ≤ 400 ng/mL
Warsaw[38]	Outside the Milan criteria but within the UCSF/ Up-to-7 criteria with AFP < 100 ng/mL
NCCK[39]	Negative PET/CT findings and the total tumor size < 10 cm
Kyoto[19]	≤ 10 tumors, all of which ≤ 5 cm in diameter, and serum DCP ≤ 400 mAU/mL
Kyushu university[40]	Tumor diameter ≤ 5 cm and serum DCP ≤ 300 mAU/mL
Extended Toronto[41]	No size-number limitation, no vascular invasion, no extrahepatic disease, no cancer-related symptoms, biopsy of the largest tumor not poorly differentiated

AFP: Alpha-fetoprotein; CT: Computed tomography; DCP: Des-gamma carboxy prothrombin; PET: Positron emission tomography; TTV: Total tumor volume.