Early screening for liver cancer must be performed

Table 1 Validated risk stratification models for hepatocellular carcinoma development

Model	Region	Derivation cohort	Variables included	Risk stratification cutoffs	Ref.
aMAP	Global	Treated chronic liver disease patients	Age, sex, bilirubin, albumin, platelet count	Low: 0-50. Intermediate: 50-60. High: 60-100	Fan et al[43], 2020
GAG-HCC	Hong Kong, China	CHB patients	Age, sex, HBV DNA level, core promoter mutations, cirrhosis	Low: < 100. High: ≥ 100	Yuen et al[72], 2009
CU-HCC	Taiwan, China, South Korea, Hong Kong	Non-cirrhotic CHB patients	Age, sex, platelet count, ALT level, HBeAg status	Low: < 5. Intermediate: 5-20. High: > 20	Kim et al[73], 2024
REACH-B	Taiwan, China	Untreated non-cirrhotic CHB patients	Age, albumin, bilirubin, HBV DNA, cirrhosis	Low: ≤ 5. Intermediate: 6-11. High: ≥ 12	Wong et al[74], 2010
LSM-HCC	Hong Kong, China	CHB patients	LSM, age, serum albumin, HBV DNA	Low: < 11. High: ≥ 11	Wong et al[75], 2014
mREACH-B	South Korea	CHB patients	Age, sex, HBeAg, LSM, ALT	Low: < 10. High: ≥ 10	Jung et al[76], 2015
HCC-RESCUE	South Korea	CHB patients on oral antivirals	Age, sex, cirrhosis	Low: < 5%. Intermediate: 5%-20%. High: ≥ 20%	Sohn et al[77], 2017
AGED	China	HBsAg-positive CHB patients	Age, sex, HBeAg status, HBV DNA level	Low: 0-4. Intermediate: 5-9. High: 10-12	Fan et al[78], 2019
CAMD	Hong Kong, Taiwan	CHB patients on ETV/TDF	Age, sex, cirrhosis, diabetes	Low: 0-7. Intermediate: 8-13. High: > 13	Hsu et al[79], 2018
PAGE-B	Europe	Caucasian CHB patients on antivirals (≥ 12 months)	Age, sex, platelet count	Low: ≤ 9. Intermediate: 10-17. High: ≥ 18	Papatheodoridis et al[80], 2016
mPAGE-B	South Korea	Asian CHB patients on antivirals (≥ 12 months)	Age, sex, platelet count, albumin	Low: 0-8. Intermediate: 9-12. High: ≥ 13	Kim et al[81], 2018
REAL-B	Asia-Pacific, United States	CHB patients on antivirals	Sex, age, alcohol use, diabetes, cirrhosis, platelet count, AFP	Low: 0-3. Intermediate: 4-7. High: 8-13	Yang et al[82], 2020
RWS-HCC	Singapore	CHB patients	Age, sex, cirrhosis, AFP	Low: < 4.5. Significant: ≥ 4.5	Poh et al[83], 2016
THRI	Canada	Cirrhosis patients	Age, sex, etiology, platelet count	Low: < 120. Intermediate: 120-240. High: > 240	Sharma et al[84], 2017
GES	Egypt	HCV cirrhosis or advanced fibrosis patients	Age, sex, albumin, AFP, pretreatment fibrosis stage	Low: ≤ 6. Intermediate: 6-7.5. High: > 7.5	Shiha et al[85], 2020
George et al	United States	NAFLD or ALD cirrhosis patients	Age, sex, BMI, diabetes, platelet count, albumin, AST/ALT ratio	Low: 0%-1%. Intermediate: > 1%-3%. High: > 3%	Ioannou et al[86], 2019
PAaM	United States	Cirrhosis (mixed etiology)	Prognostic liver secretome signature + AFP, age, male sex, ALBI, platelet count	Low: < 4.318. High: ≥ 5.072	Fujiwara et al[87], 2025

HCC: Hepatocellular carcinoma; CHB: Chronic hepatitis B; HBV: Hepatitis B virus; ALT: Alanine aminotransferase; HBeAg: Hepatitis B e antigen; LSM: Liver stiffness measurement; HBsAg: Hepatitis B surface antigen; ETV: Entecavir; TDF: Tenofovir disoproxil fumarate; AFP: Alpha-fetoprotein; HCV: Hepatitis C virus; NAFLD: Non-alcoholic fatty liver disease; ALD: Alcohol-associated liver disease; BMI: Body mass index; AST: Aspartate aminotransferase; ALBI: Albumin-bilirubin score.

Table 2 Summary of hepatocellular carcinoma prediction models based on serum biomarkers

Model name	Components/equation	Ref.
GALAD	-10.08 + 0.09 × age + 1.67 × gender + 0.04 × AFP-L3% + 2.34 × log10 AFP + 1.33 × log10 DCP	Johnson et al[88], 2014
GAAP	9.134 + 0.892 × gender + 0.073 × age + 1.057 × log10 AFP + 1.015 × log10 DCP	Liu et al[89], 2020
AALP	7.245 + 0.056 × age + 0.431 × log10 AFP + 3.112 × AFP-L3 + 1.162 × log10 PIVKA-II	Ren et al[90], 2023
ASAP	-7.577 + 0.047 × age - 0.576 × gender + 0.422 × lnAFP + 1.105 × lnDCP	Sun et al[91], 2025
GAAD	Gender, age, PIVKA-II, AFP	Piratvisuth et al[92], 2023
GAADPB	0.176 + 0.162 × gender + 0.002 × age + 0.178 × log10 AFP + 0.164 × log10 DCP - 0.007 × TP - 0.002 × TB	Chen et al[93], 2023
BALAD	Bilirubin, albumin, AFP-L3, AFP, DCP	Toyoda et al[94], 2006
BALAD-2	0.02 × (AFP-2.57) + 0.012 × (AFP-L3 - 14.19) + 0.19 × (lnDCP - 1.93) + 0.17 × (Bilirubin1/2 - 4.5) - 0.09 × (albumin - 35.11)	Fox et al[95], 2014
Doylestown	1/{1 + exp[-(-10.307 + 0.097 × age + 1.645 × gender + 2.315 × log10 AFP + 0.011 × ALP - 0.008 × ALT)]}	Wang et al[96], 2016
Doylestown Plus	Age, logAFP, PEG-precipitated IgG, fucosylated kininogen	Singal et al[97], 2022
HES V1.0	Age, current AFP level, AFP change rate, ALT, platelets	Tayob et al[98], 2021
HES V2.0	Age, current AFP level, AFP change rate, ALT, platelets, AFP-L3, DCP	El-Serag et al[99], 2025

AFP: Alpha-fetoprotein; AFP-L3: Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein; DCP: Des-gamma-carboxy prothrombin; PIVKA-II: Protein induced by vitamin K absence or antagonist-II; TP: Total protein; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; IgG: Immunoglobulin G.