Hepatocellular carcinoma: From clinical practice to evidence-based treatment protocols

Table 1 Limitations of the barcelona-clinic liver cancer staging system[78]

No	BCLC classification system
1	Does not consider nodule location, which is essential for defining respectability
2	Does not respect etiology of cirrhosis
3	Is based on variables measured at diagnosis, which might change over time
4	Does not consider the possibility of liver transplantation for patients with Child C cirrhosis with hccs within the Milan criteria
5	Does not reflect contraindications of TACE
6	Recommends liver resection to single nodules only in absence of portal hypertension in very early (BCLC 0) and early stage (BCLC A), however probably portal hypertension might not affect survival in resected patients
7	Recommends liver resection in very early (BCLC 0) and early stage (BCLC A), however in selected patients hepatic resection is associated with good survival even in more advanced BCLC stages
8	Does not consider treatment sequences or combination therapies
9	Includes a very heterogeneous population in the intermediate stage (BCLC B) in respect to tumor burden and liver function
10	Does not consider other therapies than sorafenib in selected patients with advanced stage C with performance status 1
11	Is not favorable as classification system in non-cirrhotic patients

BCLC: Barcelona-clinic liver cancer; TACE: Transarterial chemoembolization.

Table 2 Recommendations from international consensus conference on liver transplantation (only the recommendations with the highest level of evidence are presented, adopted from Clavien et al[95])

Assessment of candidates with HCC for liver transplantation

When considering treatment options for patients with HCC, the BCLC staging system is the preferred staging system to assess the prognosis of patients with HCC

The TNM system (7th ed) including pathological examination of the explanted liver, should be used for determining prognosis after transplantation with the addition of assessment of microvascular invasion

Either dynamic CT or dynamic MRI with the presence of arterial enhancement followed by washout on portal venous or delayed imaging is the best non-invasive test to make a diagnosis in cirrhotic patients suspected of having HCC and for preoperative staging

Extrahepatic staging should include CT of the chest, and CT or MRI of the abdomen and pelvis

For patients with lesions smaller or equal to 10 mm, non-invasive imaging does not allow an accurate diagnosis and should not be used to make a decision for or against transplantation

Criteria for listing candidates with HCC in cirrhotic livers for deceased donor LT

Preoperative assessment of the size of the largest tumor or total diameter of tumors should be the main consideration in selecting patients with HCC for liver transplantation

The Milan criteria are currently the benchmark for the selection of HCC patients for liver transplantation, and the basis for comparison with other suggested criteria

Biomarkers other than α-fetoprotein cannot yet be used for clinical decision making regarding liver transplantation for HCC

Indication for liver transplantation in HCC should not rely on microvascular invasion because it cannot be reliably detected prior to transplantation

Role of down-staging

Liver transplantation after successful down-staging should achieve a 5-yr survival comparable to that of HCC patients who meet the criteria for liver transplantation without requiring down-staging

Criteria for successful down-staging should include tumour size and number of viable tumours

Managing patients of the waiting list

Periodic waiting-list monitoring should be performed by imaging (dynamic CT, dynamic MRI, or contrast-enhanced US) and α-fetoprotein measurements

Patients found to have progressed beyond criteria acceptable for listing for liver transplantation should be placed on hold and considered for down-staging

Patients with progressive disease in whom locoregional intervention is not considered appropriate, or is ineffective, should be removed from the waiting list

Role of living donor LT

Living donor LT must be restricted to centers of excellence in liver surgery and liver transplantation to minimize donor risk and maximize recipient outcome

In patients following living donor LT for HCC outside the accepted regional criteria for deceased donor LT, re-transplantation for graft failure using a deceased donor organ is not recommended

Post-transplant management

Liver re-transplantation is not appropriate treatment for recurrent HCC

BCLC: Barcelona-clinic liver cancer; TACE: Transarterial chemoembolization; HCC: Hepatocellular carcinoma; LT: Liver transplantation; CT: Computed tomography; MRI: Magnetic resonance imaging.