Criteria
Milan criteria[69]
The Milan Criteria (MC) define limited-stage HCC as a solitary lesion of up to 5 cm or ≤3 lesions, each 3 cm or less, with no vascular invasion and no extrahepatic spread. Despite being relatively restrictive, the MC remains the benchmark for the selection of transplant candidates with HCC.
University of California San Francisco expanded criteria[70][71]
The University of California San Francisco expanded criteria were developed for selecting patients with HCC for liver transplantation. The criteria use cut-offs of a single lesion up to 6.5 cm in diameter or 2 or 3 lesions, each up to 4.5 cm, with total tumour diameter up to 8 cm.
Barcelona Clinic Liver Cancer (BCLC) staging[72]
American Association for the Study of Liver Diseases and European Association for the Study of the Liver practice guidelines on HCC endorse the BCLC staging system, which considers tumour burden, liver functional status, and overall physical well-being when assigning a cancer stage. The BCLC staging system also correlates each of its stages with treatment modalities and estimates the life expectancy based on prior studies.[3]
The BCLC staging system incorporates assessments of the following: performance status, single or multifocal tumour, vascular invasion, extrahepatic spread, and liver function.
This system is used to determine disease stage, treatment, and prognosis:[72]
0 - Very early stage:
performance status 0, solitary HCC ≤2 cm, no vascular invasion or extrahepatic spread, preserved liver function
A - Early stage:
performance status 0, solitary HCC lesion ≤5 cm or multifocal HCC ≤3 nodules (none of them >3 cm), preserved liver function, no macrovascular invasion or extrahepatic spread
B - Intermediate stage
performance status 0, multifocal HCC (which exceeds the BCLC-A criteria), preserved liver function, no vascular invasion or extrahepatic spread
C - Advanced stage
performance status ≤2, vascular invasion or extrahepatic spread, preserved liver function
D - End stage
performance status >2, any tumour burden, and/or impaired liver function.
Cancer of the Liver Italian Programme (CLIP) scoring system[73]
The CLIP score is calculated by assigning a score of 0, 1, or 2 for each of the following four features:
Child-Pugh stage (A, B, or C) [ Child Pugh classification for severity of liver disease (SI units) Opens in new window ]
Tumour morphology
Extent, presence of portal vein thrombosis
Serum alpha fetoprotein.
The cumulative CLIP score ranges from 0 to 6.
The higher the score, the worse the prognosis. Therefore, it is helpful for determining the treatment strategy for advanced HCC.
This scoring system is unsuitable for early-stage HCC. Furthermore, there is no significant difference in prognosis between CLIP scores 4, 5, and 6.
The CLIP score is not clinically applicable and is not used in the US.
The model for end-stage liver disease (MELD) score[74]
This numerical score, which uses laboratory values of serum creatinine, total bilirubin, and international normalised ratio, is based on objective criteria to assess a patient's risk of dying while waiting for a liver transplant. [ MELD Score for End-Stage Liver Disease (NOT appropriate for patients under the age of 12) (SI units) ]
The MELD score is a strong predictor of both peri-operative mortality and long-term survival in patients with cirrhosis undergoing hepatic resection for HCC.[75]
The MELD score ranges from 6 to 40 according to disease severity. The higher the number, the worse the prognosis.
The calculated MELD score is not useful for enlisting patients with HCC for transplant; many patients with HCC have minimal hepatic dysfunction but very high short-term mortality (not due to liver dysfunction or liver failure). The United Network for Organ Sharing, has therefore, created a policy for enlisting patients with HCC based on the Organ Procurement and Transplantation Network classification, in which tumour size and extent of tumour are used, rather than a MELD score.
United Network for Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN) diagnostic criteria for HCC for transplant listing[76]
The OPTN classification is an imaging policy of UNOS that determines the eligibility and priority for liver transplantation. For most liver transplant candidates, the MELD score is used to determine how quickly they need a transplant in the next 3 months. Certain conditions, however, such as HCC or metabolic disease, tend to be underestimated by MELD scoring; many patients with HCC have minimal hepatic dysfunction but very high short-term mortality (not due to liver dysfunction or liver failure). Patients are instead given an exception score, calculated using different criteria to MELD, and used as a substitute.
OPTN uses a distinct terminology to describe HCCs. OPTN class 5 indicates that a nodule meets radiological criteria for HCC, and class 5A or 5B lesions qualify for automatic MELD exception points:[77]
Class 5A (must meet all criteria): single nodule ≥1 cm and <2 cm measured on late arterial or portal venous phase images; increased contrast enhancement in late hepatic arterial phase; washout during later phases of contrast enhancement and peripheral rim enhancement on delayed phase (capsule or pseudocapsule) or a biopsy.
Class 5A-g (must meet all criteria): single nodule ≥1 cm and <2 cm measured on late arterial or portal venous phase images; increased contrast enhancement in late hepatic arterial phase; growth by 50% or more documented on serial CT or MRI images obtained 6 months apart.
Class 5B (must meet all criteria): single nodule ≥2 cm and ≤5 cm measured on late arterial or portal venous phase images; increased contrast enhancement in late hepatic arterial phase; either washout during later contrast phases, or peripheral rim enhancement (capsule or pseudocapsule); growth by 50% or more documented on serial CT or MRI images obtained 6 months apart (OPTN class 5B-g).
Class 5T: prior regional treatment for HCC; describes any residual lesion or perfusion defect at site of prior UNOS class 5 lesion.
Class 5X: lesions meet imaging criteria for HCC, but single nodule >5 cm, or multiple nodules >3 cm (not eligible for automatic exception points).
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