Update on the applications and limitations of alpha-fetoprotein for hepatocellular carcinoma

Table 1 Causes of alpha-fetoprotein elevation[13-15]

Hepatic	Non-hepatic
Neoplastic	Neoplastic
Hepatocellular carcinoma	Germ cell tumors (testicular and ovarian malignancies)
Intrahepatic cholangiocarcinoma	Gastric cancer
Non-neoplastic	Non-neoplastic
Liver cirrhosis	Normal pregnancy/infancy
Fulminant acute hepatitis	Colitis
Acute and chronic viral hepatitis	Fetal disorders (Gastroschisis, Neural tube defect)
Chronic liver diseases	Ataxia telangiectasia
Biliary obstruction (Intrahepatic and extrahepatic causes)	Hereditary tyrosinemia type 1
Drug induced hepatitis	Hereditary AFP persistence
Alcohol liver disease	Beckwith-Wiedemann syndrome
Non-alcoholic liver disease	Systemic lupus erythematosus
Neonatal hepatitis	Hirschsprung’s disease
Massive hepatic necrosis
Wilson disease
Hemochromatosis

AFP: Alpha-fetoprotein.

Table 2 Sensitivity and specificity of alpha-fetoprotein at different cut-off values[22-24]

AFP cut-off value	Sensitivity	Specificity
20	Approximately 60%	90%
50	47%	96%
100	31.2%	98.8%
400	17%	99.4%

AFP: Alpha-fetoprotein.

Table 3 Overview of the diagnostic parameters for hepatocellular carcinoma

Diagnostic parameter (cut off)	Remark	AUROC
AFP (> 20 ng/mL)	Sensitivity: 40%–65%	0.54–0.80
	Specificity: 76%–96%
AFP-L3 (> 15%)	Sensitivity: 45%–90%	0.74–0.84
	Specificity: 95%
AFP-L3 + AFP-P4 + P5 (> 15% for both biomarkers)	Sensitivity: 55.3%–61%	0.76
	Specificity: 82.3%–93.9%
AFP, AFP-L3 and DCP (3-25 ng/mL, 1%-10%, 0.48 ng/mL or 40 mAu/mL)	Sensitivity: 81%–93%	0.88–0.93
	Specificity: 69%-87%
AFP and GP73	Sensitivity: 75%-91%	0.91–0.95
	Specificity: 81%-97%

AFP: Alpha-fetoprotein; DCP: Des-gamma-carboxyprothrombin.