From diagnosis to treatment of hepatocellular carcinoma: An epidemic problem for both developed and developing world

Table 1 Barcelona Clinic Liver Cancer staging classification

Tumor status
Stage	PST	Tumor stage	Okuda Stage	Liver function studies
Stage A: early HCC
A1	0	Single	I	No portal hypertension
A2	0	Single	I	Portal hypertension and normal bilirubin
A3	0	Single	I	Portal hypertension and abnormal bilirubin
A4	0	3 tumors < 3 cm	I-II	Child-Pugh A-B
Stage B: idermediate HCC	0	Large multinodular	I-II	Child-Pugh A-B
Stage C: advanced HCC	1-21	Vascular invasion or extrahepatic spread	I-II	Child-Pugh A-B
Stage D: end-stage HCC	3-42	Any	III	Child-Pugh C

¹Stage C, at least one criteria: PST1-2 or vascular invasion/extrahepatic spread;

²Stage D, at least one criteria: PST3-4 or Okuda Stage III/Child-Pugh C. PST: Performance status; Stage A and B, all criteria should be fulfilled.

Table 2 Child-Turcotte-Pugh score

Measurements	Score
	1	2	3
Encephalopathy	None	Mild	Moderate
Ascites	None	Slight	Moderate
Serum Bilirubin (mg/dL)	1-2	2-3	> 3
Serum Albumin (mg/dL)	> 3.5	2.8-3.5	< 2.8
PT (seconds prolonged)	< 4	4-6	> 6

Stage A: 5-6 points; Stage B: 7-9 points; Stage C: 10-15 points.

Table 3 Model for end-stage liver disease, United Network for Organ Sharing modification

MELD Score = 9.57 × ln (Serum Creatinine in mg/dL)

+ 3.78 × ln (Serum Bilirubin in mg/dL)

+ 11.2 × ln (INR) + 6.43

MELD: Model for end-stage liver disease.

Table 4 American Joint Committee on Cancer TNM Staging for Liver Tumors (7^th edition, 2010)

Primary tumor (T)
Tx	Primary tumor cannot be assessed
T0	No evidence of primary tumor
T1	Solitary tumor without vascular invasion
T2	Solitary tumor with vascular invasion or multiple tumors, none more than 5 cm
T3a	Multiple tumors more than 5 cm
T3b	Single tumor or multiple tumors of any size involving a major branch of the portal vein or the hepatic vein
T4	Tumors with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum
Regional lymph nodes (N)
Nx	Regional lymph nodes cannot be assessed
N0	No regional node metastasis
N1	Regional lymph node metastasis
Distal Metastases (M)
M0	No distant metastasis
M1	Distant metastasis
Anatomic stage/prognostic groups
Stage I	T1	N0	M0
Stage II	T2	N0	M0
Stage IIIA	T3a	N0	M0
Stage IIIB	T3b	N0	M0
Stage IIIC	T4	N0	M0
Stage IςA	Any T	N1	M0
Stage IςB	Any T	Any N	M1
Histologic grade (G)
G1	Well differentiated
G2	Moderately differentiated
G3	Poorly differentiated
G4	Undifferentiated
Fibrosis core (F)
The fibrosis score as defined by Ishak recommended because of its prognostic value in overall survival. This scoring system uses a 0-6 scale
F0	Fibrosis score 0-4 (none to moderate fibrosis)
F1	Fibrosis score 5-6 (severe fibrosis or cirrhosis)

Table 5 Current treatment options for hepatocellular carcinoma

Surgical

Resection

Resection + ablation

Orthotopic liver transplantation

Ablative

Thermal ablation (radiofrequency ablation, microwave ablation)

Percutaneous alcohol (ethanol) injection

Transarterial

Embolization

Chemoembolization

Radiotherapy

Transarterial and ablative (combined)

Systemic chemotherapy + radioembolization

Table 6 Treatment schedule proposed for hepatocellular carcinoma cirrhotic patients according to the Barcelona Clinic Liver Cancer classification system

Stage	Treatment intention	First/second choice
Stage A: early HCC
A1	Radical	Surgical resection
A2		Surgical resection ð OLT/percutaneous treatment
A3		OLT/percutaneous treatment (Ablation)
A4		OLT/percutaneous treatment (Ablation)
Stage B: intermediate HCC	Palliative1	Trasanterial embolization (associated or not to percutaneous treatment)
		Chemoembolization (TACE)
Stage C: advanced HCC	Palliative1	New agents (Sorafenib)
Stage D: end-stage HCC	Symptomatic	Supporting treatment

¹In the setting of phase II investigations or randomized control trials. HCC: Hepatocellular carcinoma; BCLC: Barcelona Clinic Liver Cancer.