Prediction models for development of hepatocellular carcinoma in chronic hepatitis B patients

Table 1 Risk scores for prediction of hepatocellular carcinoma in untreated chronic hepatitis B patients

Ref.	Risk score	Patients in derivation, n	Country or area	Age (yr)	HBeAg-positive, n (%)	Cirrhosis in Derivation, n (%)	Follow-up (yr), median	Antiviral therapy during follow-up, n (%)	Variables of the risk score	AUROC for 5 yr	Cut-off
Yuen et al[21]	GAG-HCC	820	Hong Kong	40.6 (13.5-83.2)	356 (43.4)	124 (15.1)	6.6	0	Age, sex, HBV DNA, cirrhosis, Core promoter mutation	0.88	101
Wong et al[16]	CU-HCC	1005	Hong Kong	48 ± 7	-	383 (38.1)	9.9	152 (15.1)	Age, albumin, bilirubin, cirrhosis, HBV DNA	0.76	Low-risk < 5; Intermediate risk 5-19; High risk ≥ 19
Yang et al[22]	REACH-B	3584	Taiwan	45.7 ± 9.8	545 (15.2)	0	12.0	0	Age, sex, ALT, HBeAg, HBV DNA	0.796	-
Lee et al[24]	REACH-B II	2227	Taiwan	30-65	-	0	-	0	Sex, age, ALT, family history of HCC, HBeAg, HBV DNA, HBsAg, genotype	0.89	-
Wong et al[29]	LSM-HCC	1035	Hong Kong	46 ± 12	256 (24.7)	331 (32.0)	5.8	390 (37.8)	Age, albumin, HBV DNA, LSM	0.83	11
Poh et al[30]	RWS-HCC	538	Singapore	56.4 ± 12.1	167 (31.0)	80 (14.9)	4.9	-	Sex, age, cirrhosis, AFP	0.9151	4.5
Sinn et al[31]	D2AS risk score	971	South Korea	42.6 ± 10.6	547 (56.3)	0	4.5	0	HBV DNA, sex, age	0.884	Very low < 1; Low-risk 1.0-1.9; Intermediate risk 2.0-2.4; High risk ≥ 2.5
Fung et al[33]	HCC-ESC	723	Hong Kong	32 (18-83)	723 (100)	-	18.3	427 (59.1)	Age, sex, cirrhosis, HBV DNA, ALT, albumin	0.95	129
Fan et al[34]	AGED	628	Chinamainland	-	193 (30.7)	0	21.0	-	Age, sex, HBeAg, HBV DNA	0.76	Low-risk 0-4; Intermediate risk 5-9; High risk 10-12

¹Ten-year hepatocellular carcinoma prediction. HBeAg: Hepatitis B e antigen; AUROC: Area under the receiver operating characteristic curve; GAG-HCC: Guide with age, gender, hepatitis B virus DNA, core promoter mutations and cirrhosis; CU-HCC: Chinese University-hepatocellular carcinoma; REACH-B: Risk estimation for hepatocellular carcinoma in chronic hepatitis B; LSM: Liver stiffness measurement; RWS: Real-world score; ESC: Hepatitis B e antigen seroclearance; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; HBsAg: Hepatitis B surface antigen.

Table 2 Risk scores for prediction of hepatocellular carcinoma in treated chronic hepatitis B patients at baseline

Ref.	Risk score	Patients in derivation, n	Country or area	Age (yr)	HBeAg-positive, n (%)	Cirrhosis in derivation, n (%)	Follow-up (yr), median	Variables of the risk score	AUROC for 5- yr	Cut-off
Lee et al[35]	mREACH-B	192	South Korea	49 (42-56)	100 (52.1)	90 (46.9)	3.6	Age, sex, ALT, HBeAg, LSM	0.8051	-
Papatheodoridis et al[37]	PAGE-B	1325	Europe	52 ± 21	210 (15.8)	269 (20.3)	4.2	Age, sex, platelets	0.82	Low-risk ≤ 9; Intermediate risk 10-17; High risk ≥ 18
Sohn et al[43]	HCC-RESCUE	990	South Korea	47.4 ± 10.5	556 (56.2)	389 (39.3)	2.1	Age, sex, cirrhosis	0.768	Low-risk ≤ 64; Intermediate risk 65-84; High risk ≥ 85
Hsu et al[44]	CAMD	23851	South Korea	47.5 (37.8-56.5)	-	6308 (26.4)	2.2	Age, sex, diabetes, cirrhosis	0.821	Low-risk < 8; Intermediate risk 9-13; High risk > 13
Kim et al[46]	mPAGE-B	2001	South Korea	50 (42-57)	678 (33.9)	383 (19.1)	4.1	Age, sex, platelets, albumin	0.82	Low-risk ≤ 8; Intermediate risk 9-12; High risk ≥ 13
Yu et al[47]	AASL	944	South Korea	50 (41-57)	528 (55.9)	371 (39.3)	4.1	Age, sex, albumin, cirrhosis	0.802	Low-risk ≤ 5; Intermediate risk 6-19; High risk ≥ 20
Liang et al[48]	LSM-HCC and ELF	453	Hong Kong	51.7 ± 10.3	155 (36.1)	-	4.7	Age, albumin, HBV DNA, LSM, ELF	-	LSM-HCC 20 or ELF 9.8
Yang et al[50]	REAL-B	5365	United States and Asia-Pacific area	48.4 ± 12.7	1886 (37.4)	1085 (20.2)	-	Age, sex, alcohol, diabetes, cirrhosis, platelet, AFP	0.80	Low-risk 0-3; Intermediate risk 4-7; High risk 8-13
Lee et al[51]	CAMPAS	1511	South Korea	49.7 (42.1-56.2)	795 (52.6)	602 (39.8)	-	Age, sex, cirrhosis, platelet, albumin, LSM	0.8842	Low-risk ≤ 75; Intermediate risk 75-161; High risk > 161

¹Three-year hepatocellular carcinoma prediction.

²7-yr hepatocellular carcinoma prediction. HBeAg: Hepatitis B e antigen; AUROC: Area under the receiver operating characteristic curve; mREACH-B: Modified Risk estimation for hepatocellular carcinoma in chronic hepatitis B; PAGE-B: Platelet, age, and gender-hepatitis B; mPAGE-B: Modified platelet, age, and gender-hepatitis B; CAMD: Cirrhosis, age, male sex, and diabetes mellitus; AASL: Age, albumin, sex, liver cirrhosis; LSM: Liver stiffness measurement; REAL-B: Real-world Effectiveness from the Asia Pacific Rim Liver Consortium for hepatitis B virus; ALT: Alanine aminotransferase; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; ELF: Enhanced liver fibrosis; AFP: α-fetoprotein.

Table 3 Risk scores for prediction of hepatocellular carcinoma in treated chronic hepatitis B patients during treatment

Ref.	Score	Patients in derivation, n	Country or area	Age (yr)	HBeAg-positive, n (%)	Cirrhosis in derivation, n (%)	Follow-up (yr), median	Variables of the risk score	AUROC for 5 yr	Cut-off
Chen et al[54]	APA-B	883	Taiwan	50 ± 17	311 (35.2)	317 (35.9)	4.1	Age, platelets, AFP at 12 mo	0.827	Low-risk 0-5; Intermediate risk 6-9; High risk 10-15
Lim et al[56]	HCC-ESCAVT	769	South Korea	47.0 (37.0-55.0)	0	319 (41.5)	-	Sex, age, cirrhosis, ALT, AST, platelet	0.771	Low-risk 0-1; Intermediate risk 2-4; High risk 5
Papatheodoridis et al[58]	CAGE-B	1427	Europe	52.1 ± 13.1	261 (18.4)	370 (25.9)	8.4	Age, LSM at year 5, baseline cirrhosis	0.814	Low-risk 0-5; Intermediate risk 6-10; High risk 11-16
Papatheodoridis et al[58]	SAGE-B	1427	Europe	52.1 ± 13.1	261 (18.4)	370 (25.9)	8.4	Age, LSM at year 5	0.809	Low-risk 0-5; Intermediate risk 6-10; High risk 11-16

HBeAg: Hepatitis B e antigen; AUROC: Area under the receiver operating characteristic curve; HCC: Hepatocellular carcinoma; ESC: Hepatitis B e antigen seroclearance; AVT: Antiviral therapy; CAGE-B: Cirrhosis and age; SAGE-B: Stiffness and age; AFP: α-Fetoprotein; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; LSM: Liver stiffness measurement.