Development and application of hepatocellular carcinoma risk prediction model based on clinical characteristics and liver related indexes

doi:10.4251/wjgo.v15.i8.1486

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World Journal of Gastrointestinal Oncology

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World J Gastrointest Oncol. Aug 15, 2023; 15(8): 1486-1496
Published online Aug 15, 2023. doi: 10.4251/wjgo.v15.i8.1486

Table 1 Characteristics of the study population (n = 2206)

Characteristic	Training cohort		Validation cohort
Characteristic	HCC (n = 496)	Non-HCC (n = 1243)	HCC (n = 156)	Non-HCC (n = 311)
Age (yr)	57.86 ± 11.89^a	53.84 ± 14.53	58.47 ± 11.87^b	54.33 ± 13.53
Gender
Male, n (%)	411 (82.9)^a	759 (61.1)	131 (84.0)^b	169 (54.3%)
Female, n (%)	85 (17.1)^a	484 (38.9)	25 (16.0)^b	142 (45.7%)
PIVKA-II, mAU/mL	1321.03 (117.91-9792.97)^a	24.04 (18.21-37.02)	1337.95 (92.76-11380.07)^b	22.69 (16.92-32.41)
AFP, ng/mL	178.65 (8.33-6474.00)^a	3.60 (1.80-11.75)	145.45 (6.25-2439.10)^b	3.70 (1.90-8.75)
TBIL, μmol/L	21.20 (15.60-31.85)^a	29.80 (15.70-127.50)	21.20 (14.43-32.73)^b	27.40 (15.45-94.05)
GGT, IU/L	130.00 (59.75-279.75)^a	78.20 (29.00-197.00)	145.40 (60.75-272.75)^b	63.00 (25.00-168.35)
AST, U/L	61.10 (38.00-110.00)^a	56.00 (28.00-178.00)	60.00 (37.00-102.83)^b	49.00 (25.00-147.80)
ALT, U/L	42.00 (26.00-70.00)^a	44.00 (21.00-210.85)	43.00 (25.57-68.00)^b	37.00 (19.50-149.00)
TBA, μmol/L	11.10 (4.50-27.45)^a	18.80 (4.10-123.95)	10.20 (4.27-22.10)^b	16.20 (4.00-97.45)
ALB, g/L	37.10 (32.30-41.40)^a	36.10 (30.00-42.20)	37.75 (34.00-41.42)^b	36.80 (30.85-41.90)
HBsAg
Positive, n (%)	388 (78.2)^a	555 (44.7)	123 (78.8)^b	131 (42.1)
Negative, n (%)	108 (21.8)^a	688 (55.3)	33 (21.2)^b	180 (57.9)
Child Pugh Class
Class A, n (%)	317 (63.9)^a	583 (46.9)	103 (66.0)^b	155 (49.8)
Class B, n (%)	151 (30.4)^a	430 (34.6)	45 (28.8)^b	103 (33.1)
Class C, n (%)	28 (5.6)^a	230 (18.5)	8 (5.1)^b	53 (17.0)

^aP < 0.05, compared with non-hepatocellular carcinoma group in training cohort.

^bP < 0.05, compared with non-hepatocellular carcinoma group in validation cohort.

Data are presented as mean standard deviation, median (interquartile range), or numbers (%). HBsAg: Hepatitis B surface antigen; TBA: Total bile acid; TBIL: Total bilirubin; GGT: Gamma-glutamyl transferase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; AFP: Alpha-fetoprotein; PIVKA-II: Protein induced by vitamin K absence or antagonist-II; HCC: Hepatocellular carcinoma; ALB: Albumin.

Table 2 Alpha-fetoprotein, protein induced by vitamin K absence or antagonist-II, or both in the diagnosis of hepatocellular carcinoma

	Training cohort					Validation cohort
	AUC (95%CI)	SEN (%)	SPE (%)	PPV (%)	NPV (%)	AUC (95%CI)	SEN (%)	SPE (%)	PPV (%)	NPV (%)
HCC
AFP	0.812 (0.788-0.815)	49.19	93.00	42.21	94.63	0.845 (0.786-0.880)	52.56	91.00	49.04	92.09
PIVKA-II	0.882 (0.865-0.903)	63.91	94.93	51.21	96.93	0.878 (0.839-0.916)	64.74	94.53	57.35	95.93
AFP + PIVKA-II	0.896 (0.877-0.915)	69.35	95.82	55.51	97.65	0.888 (0.851-0.924)	67.95	95.17	59.83	96.56
Early-stage HCC
AFP	0.860 (0.792-0.928)	51.06	97.49	82.77	89.40	0.714 (0.642-0.787)	14.55	98.49	72.70	80.66
PIVKA-II	0.863 (0.790-0.936)	40.43	96.98	75.97	87.33	0.868 (0.802-0.935)	52.73	96.48	80.55	88.07
AFP + PIVKA-II	0.923 (0.869-0.978)	63.83	96.98	83.31	91.90	0.869 (0.804-0.933)	50.91	95.98	77.78	87.61

SEN: Sensitivity; SPE: Specificity; PPV: Positive predictive value; NPV: Negative predictive value; CI: Confidence interval; PIVKA-II: Protein induced by vitamin K absence or antagonist-II; HCC: Hepatocellular carcinoma; AUC: Area under receiver operating characteristic curve; AFP: Alpha-fetoprotein.

Table 3 Diagnostic performance of hepatocellular carcinoma, early hepatocellular carcinoma, and different subgroups of hepatocellular carcinoma in the NSMC-hepatocellular carcinoma model

	Cut-off value	Training cohort					Validation cohort
	Cut-off value	AUC (95%CI)	SEN (%)	SPE (%)	PPV (%)	NPV (%)	AUC (95%CI)	SEN (%)	SPE (%)	PPV (%)	NPV (%)
HCC	0.22	0.960 (0.950-0.971)	94.40	95.35	87.25	98.10	0.966 (0.945-0.986)	90.00	94.20	89.87	95.47
Early HCC		0.946 (0.901-0.991)	85.93	93.62	61.11	98.28	0.947 (0.901-0.994)	89.10	98.49	94.23	97.02

SEN: Sensitivity; SPE: Specificity; PPV: Positive predictive value; NPV: Negative predictive value; CI: Confidence interval; HCC: Hepatocellular carcinoma; AUC: Area under receiver operating characteristic curve; AFP: Alpha-fetoprotein.

Table 4 Proposed risk scale and corresponding probability of predictive risk of hepatocellular carcinoma

Risk level	Probability of risk	PPV (%)	NPV (%)
Low risk	0.000-0.007	NA	≥ 99.00
Moderate risk	0.008-0.220	NA	< 99.00
High risk	0.221-0.940	< 99.00	NA
Most likely HCC	0.941-1.000	≥ 99.00	NA

NA: Not applicable; PPV: Positive predictive value; NPV: Negative predictive value; HCC: Hepatocellular carcinoma.

Citation: Liu ZJ, Xu Y, Wang WX, Guo B, Zhang GY, Luo GC, Wang Q. Development and application of hepatocellular carcinoma risk prediction model based on clinical characteristics and liver related indexes. World J Gastrointest Oncol 2023; 15(8): 1486-1496
URL: https://www.wjgnet.com/1948-5204/full/v15/i8/1486.htm
DOI: https://dx.doi.org/10.4251/wjgo.v15.i8.1486