Biomarkers vs imaging in the early detection of hepatocellular carcinoma and prognosis

Table 1 International guidelines for hepatocellular carcinoma surveillance programs

Guideline	Indications	AFP	Imaging	Period (mo)
WHO	HBV DNA > 2000 UI/mL, HCV cirrhosis	+	US	6
Canadian	Cirrhosis, HBV chronic carriers		US	6
AASLD	Cirrhosis	+/-	US	6
NCCN	Cirrhosis, HBV chronic hepatitis	+/-	US	6
Australian			US
EASL			US	6
Japan	Cirrhosis	+	US/dynamic CT/MRI	3-6
Asia-Pacific		> 200 ng/mL	US	6

AASLD: American Association for the Study of Liver Diseases; CT: Computed tomography; EASL: European Association for the Study of the Liver; HBV: Hepatitis B virus; HCV: Hepatitis C virus; MRI: Magnetic resonance imaging; NCCN: National Comprehensive Cancer Network; US: Ultrasonography; WHO: World Health Organization.

Table 2 International guidelines for hepatocellular carcinoma diagnosis

Guideline	Liver nodule US	Biomarkers	Indications for biomarkers
Canadian	CT/MRI/CEUS	AFP, AFP-L3, DCP	Late stage/aggressive
AASLD	CT/MRI
ACG	CT/MRI
NCCN	CT/MRI
Australian	CT/MRI/CEUS: Selected case
EASL	CT/MRI/CEUS
ESMO	CT/MRI
Japan	CT/MRI	AFP, AFP-L3, DCP	Definitive diagnosis, efficacy of treatment
Asia-Pacific	CT/MRI/CEUS

AFP: Alpha-fetoprotein; AFP-L3: Alpha-fetoprotein L3; AASLD: American Association for the Study of Liver Diseases; CEUS: Contrast-enhanced computed tomography; CT: Computed tomography; DCP: Des-gamma-carboxyprothrombin; EASL: European Association for the Study of the Liver; ESMO: European Society for Medical Oncology; MRI: Magnetic resonance imaging; NCCN: National Comprehensive Cancer Network; US: Ultrasonography.

Table 3 MicroRNAs in hepatocellular carcinoma

miRNA	Hepatitis virus	Ref.
For early diagnosis
exosomal hnRNPH1 miR	HBV	Xu et al[55]
miR-26	HBV	Balkan et al[56]
miR-88	HBV	Long et al[57]
mi-R-106b		Shi et al[58]
miR-125b		Liu et al[59]
miR-4463		Hu et al[60]
miR-10a, miR-122, miR-375, miR-423	HBV	An et al[61]
miR-10b, miR-106b, miR-181a	HBV	Jiang et al[62]
miR-17-5p, miR-29a, miR-106a, miR-122, miR-125b, miR-145, miR-192, miR-194	HBV	Xue et al[63]
miR-21, mi-R106b, mi-R224	HBV	Liu et al[64]
miR-21		Liao et al[65]
miR-21, miR-122, miR-199		Ding et al[66]
miR-25, miR-375, let-7f		Xu et al[67]
miR-122, miR-148a, AFP	HBV	Wang et al[68]
miRNA-23a	HCV	Mohamed et al[69]
miR-19a, miR-146a, miR-192, and miR-195	HCV	Motawi et al[70]
miR-122, miR-224	HCV	Amr et al[71]
miR-125b, miR-214-5p, miR-375, miR-1269	HCV	Elemeery et al[72]
miR-595, miR-939	HCV	Fornari et al[73]
For overall survival and prognosis
miR-106a	HBV	Xue et al[63]
miR-128-2	HBV	Zhuang et al[74]
miR-192-5p and miR-29a-3p	HBV	Zhu et al[75]
miR-23a	HCV	Mohamed et al[69]

HBV: Hepatitis B virus; HCV: Hepatitis C virus.

Table 4 LncRNAs in hepatocellular carcinoma

LncRNA	Hepatitis virus	Ref.
For early diagnosis
LINC00152, RP11-160H22.5 and XLOC014172	HBV	Yuan et al[80]
uc001ncr and AX800134	HBV	Wang et al[81]
RP11–160H22.5, XLOC_014172 and LOC149086	HBV	Tang et al[82]
UCA I	HBV	Zheng et al[83]
ENSG00000258332.1, LINC00635	HBV	Xu et al[84]
LINC00152, RP11-160H22.5, XLOC014172, LOC149086 or HULC, Linc00152 or uc001ncr, AX800134 or PVT1, uc002mbe.2		Chen et al[85]
Predictors for poor prognosis
BANCR		Qin et al[88]
XLOC_014172 and LOC149086	HBV	Tang et al[82]
UCA I	HBV	Zheng et al[83]

HBV: Hepatitis B virus; HCV: Hepatitis C virus; lncRNA: Long non-coding RNA.