Non-invasive tests for the prediction of primary hepatocellular carcinoma

Table 1 Studies reporting the role of aspartate aminotransferase to platelet ratio index in predicting hepatocellular carcinoma

Ref.	Etiology	Patients(n)	Follow-up (mo)	Region	HCC(n)	AUROC	Cut-off
Yu et al[31], 2006	HCV IFN-based treated	776	62.5	Asia	41	0.870	0.75 all patients 0.5 SVR, 1.5 no-SVR
Yu et al[31], 2006	HCV untreated	562	61.8	Asia	54	0.715	1.5
Reddy et al[33], 2015	HCV SVR IFN-treated	22	96	America	0	-	-
Reddy et al[33], 2015	HCV untreated	203	96	America	51	-	-
Hann et al[34], 2015	HBV	855	52.4	America; Asia	82	-	-
Chen et al[35], 2016	HCV SVR	540	41.4	Asia	15	-	> 0.5
Chen et al[35], 2016	HCV (no-SVR)	183	36.8	Asia	14	-	> 1.5
Kim et al[36], 2016	HBV	542	60	Asia	68	0.731	> 0.766
Lee et al[37], 2016	HCV	598	61.2	Asia	8		1
Ng et al[38], 2016	HCV	105	40.56	Asia	15	-	2
Wu et al[39], 2016	HCV SVR	1351	6 after SVR	Asia	49	-	0.7
Toyoda et al[21], 2017	HCV SVR; Training cohort	522	104	Asia	21	-	0.73
Toyoda et al[21], 2017	HCV SVR; Validation cohort	309	87,6	Asia	17	-	0,73
Cheung et al[22], 2017	PBC	144	82.8	Asia	12	0.77	0.54
Nishikawa et al[23], 2017	HBV	338	59.8	Asia	33	0.601	0.78
Ji et al[24], 2017	HCV SVR	34	41.4	Asia	5		1.5
Paik et al[16], 2018	HBV	1006	61.2	Asia	36	0.76	0.5
Chang et al[25], 2018	HCV (no-SVR)	800	53.5	Asia	100	-	2.57
Kim et al[26], 2018	ALD	924	36	Asia	83	0.61	1
Song et al[27], 2018	HBV	1014	46.8	Asia	37	-	0.5
Sou et al[28], 2018	HCV SVR; IFN-treatment	1351	6 after SVR	Asia	47	-	0,7
Sou et al[28], 2018	HCV no SVR	536	6 post treatment	Asia	75	-	0,7
Na et al[20], 2019	HCV SVR	295	89.2	Asia	12	0.89	2
Yoshimasu et al[29], 2019	HCV DAAs	211	6 after DAAs	Asia	2	-	-
Sahin et al[30], 2019	HBV; HBV+HDV	361	-	Europe	115	-	-
Kim et al[32], 2020	HBV	444	94.2	Asia	25	0.572	-

HCC: Hepatocellular carcinoma; AUROC: Area under receiving operating characteristics curve; HCV: Hepatitis virus C; IFN: Interferon; SVR: Sustained virologic response; HBV: Hepatitis virus B; PBC: Primary biliary cholangitis; ALD: Alcoholic liver disease; DAA: Direct acting antiviral agents; HDV: Hepatitis D virus.

Table 2 Studies reporting the role of fibrosis-4 index in predicting hepatocellular carcinoma

Ref.	Etiology	Patients (n)	Follow-up (mo)	Region	HCC (n)	AUROC	Cut-offs
Park et al[44], 2011	HIV with HCV, HBV, ALD	22980	-	United States	112	-	1.45–3.25; > 3.25
Chon et al[49], 2012	HBV	1126	30.7	Asia	63	0.744	-
Tamaki et al[50], 2014	HCV	1046	76.8 – 70.8	Asia	119	0.61	> 3.25; > 3.25 + ΔFIB-4/ year ≥ 0.3; ΔFIB-4/ year ≥ 0.3
Ito et al[51], 2015	HCV	516	135.6	Asia	60	-	2.0-4.0; > 4
Toyoda et al[52], 2015	HCV SVR	522	86.4	Asia	18	-	> 2 (at SVR24)
Suh et al[47], 2015	HBV	986	64.8	Asia	-	-	1.7–2.4; > 2.4
Suh et al[46], 2015	ALD	6661	74.4	Asia	-	-	1.75 –2.1; > 2.1
Kim et al[36], 2016	HBV	542	60	Asia	68	0.803	2.225
Fusco et al[53], 2016	HBV, HCV, none	4492	96	Europe	22	-	3.25
Tseng et al[48], 2017	HBV naive HBV NU	2075 (+532)	192.2	Asia	137 (+10)	0.75	1.29
Nishikawa et al[23], 2017	HBV	338	60	Asia	33	0.768	3.666
Butt et al[54], 2017	HCV	21116	12/36/60	United States	-	0.81 - 0.82	1.45
Kim et al[26], 2018	ALD	924	36	Asia	83	0.69	3.5
Chang et al[25], 2018	HCV no SVR	800	53.5	Asia	100	-	2.83
Peleg et al[55], 2018	NAFLD	153	100	Israel	6	-	2.67
Song et al[27], 2018	HBV	1014	46.8	Asia	37	-	1.45
Paik et al[16], 2018	HBV	1006	61.2	Asia	36	0.71	1.45
Kanwal et al[45], 2019	HCV SVR post-DAA	18076	43,8	United States	544	-	3.25; 1.45
Ioannou et al[56], 2019	HCV SVR	48135	64.8	United States	1509	-	3.25
Alexander et al[57], 2019	NAFLD	63971 (Fib-4 available)	39.6	Europe	-	-	2.67
Na et al[20], 2019	HCV SVR	295	89.2	Asia	12	0.86 0.85	3.25 (pre-SVR); 2.5 (SVR)
Li et al[58], 2019	HCV	711	-	Asia	249	0.961	2.18
Watanabe et al[59], 2019	HCV SVR post -DAA	1174	17.9	Asia	35	-	4
Degasperi et al[60], 2019	HCV SVR post -DAA	565	25	Europe	48	-	9
Kim et al[32], 2020	HBV	444	84	Asia	25	0.753 (60 mo); 0.698 (84 mo)	3.25

HCC: Hepatocellular carcinoma; AUROC: Area under receiving operating characteristics curve; HIV: Human immunodeficiency virus; HCV: Hepatitis virus C; HBV: Hepatitis virus B; ALD: Alcoholic liver disease; ∆: Delta; SVR: Sustained virologic response; NU: Nucleoside analogues; NAFLD: Non-alcoholic fatty liver disease; DAA: Direct acting antiviral agents.

Table 3 Studies reporting the role of transient elastography in predicting hepatocellular carcinoma

Ref.	Etiology	Patients (n)	Follow-up (mo)	Region	HCC (n)	AUROC	Cut-off (kPa)
Masuzaki et al[110], 2008	HCV	265	-	Asia	85	0.805	25
Nahon et al[116], 2009	HCV	265	-	Europe	66	-	-
Masuzaki et al[115], 2009	HCV	866	36.0	Asia	77	-	25
Kuo et al[117], 2010	HBV, HCV, non-B/non-C	435	-	Asia	106	0.736	24
Akima et al[118], 2011	Mixed (HCV: 85%)	157	40.7	Asia	41	0.787	12.5
Jung et al[90], 2011	HBV	1130	30.7	Asia	57	-	8
Fung et al[91], 2011	HBV	528	35.0	Asia	7	-	10
Robic et al[94], 2011	Mixed	100	24.0	Europe	4	0.837	21.1
Klibansky et al[95], 2012	Mixed	667	28.7	USA	16	0.870	10.5
Chon et al[49], 2012	HBV	1126	30.7	Asia	63	0.789	-
Kim et al[92], 2012	HBV	128	27.8	Asia	13	0.722	19
Calvaruso et al[97], 2012	HCV/HIV	275	32	Europe	-	-	14-40
Salmon et al[98], 2012	HCV/HIV	244	30	Europe	21	-	12.5
Perez-Latorre et al[99], 2013	HCV	60	42	Europe	7	0.77	25-40
Feier et al[89], 2013	HCV	144	-	Europe	72	0.680	38.5
Wang et al[119], 2013	HCV	198	47.8	Asia	10	-	12
Narita et al[120], 2013	HCV	151	24.1	Asia	9	-	14
Kim et al[93], 2013	HBV	162	24.0	Asia	12	0.736	12
Poynard et al[96], 2014	HCV	3927	144	Europe	84	0.860	50
Wong et al[100], 2014	HBV	1555	69	Asia	55	0.83	11
Kim et al[102], 2015	HBV	2876	48.9	Asia	52	0.532	13
Wang et al[103], 2016	HCV	278	91.2	Asia	18	0.781	12
Adler et al[105], 2016	Mixed	432	31.3	Europe	41	-	20
Bihari et al[106], 2016	HBV	964	-	Asia	14	0.767
Seo et al[107], 2016	HBV	381	48.1	Asia	34	0.745	-
Jeon et al[104], 2017	HBV	540	54.1	Asia	81	0.598	13
Li et al[101], 2017	HBV	1200	48	Asia	156	-	-
D’Ambrosio et al[108], 2018	HCV	404	36	Europe	24	-	-
Wang et al[109], 2019	HBV	371	67.2	Asia	27	0.636	21.5
Degasperi et al[60], 2019	HCV SVR	546	25	Europe	28	-	30
Rinaldi et al[111], 2019	HCV SVR	258	24	Europe	35	0.691	27.8
Izumi et al[112], 2019	HCV	419	30	Asia	32	0.806	8
Izumi et al[112], 2019	HBV	377	27	Asia	23	0.795	6.2
Izumi et al[112], 2019	NAFLD	258	30	Asia	33	0.698	5.4
Pons et al[113], 2019	HCV SVR	572	33	Europe	25	-	-
Nakagomi et al[114], 2019	HCV	1146	78	Asia	190	-	-

AUROC: Area under receiving operating characteristics curve; kPa: Kilopascal; HCV: Hepatitis virus C; HBV: Hepatitis virus B; HIV: Human immunodeficiency virus; SVR: Sustained virologic response; NAFLD: Non-alcoholic fatty liver disease.