Multi-clustering study on the association between human leukocyte antigen-DP-DQ and hepatitis B virus-related hepatocellular carcinoma and cirrhosis in Viet Nam

Table 1 Clinical characteristics of study subjects

Variable		Healthy control (n = 315)	CHB (n = 471)	HBV-related LC (n = 250)	HBV-related HCC (n = 251)	HBV carrier (n = 972)
Age, mean ± SD		52.78 ± 11.63	50.43 ± 14.67	54.75 ± 13.36	55.99 ± 9.91	52.98 ± 13.48
Age	< 60	237	353	165	165
	≥ 60	78	118	85	86
Gender	Male	244	367	190	212	769
	Female	71 (22.5)	104 (22.1)	60 (24.0)	39 (15.5)	203 (20.9)
ALT		24.92 ± 11.93	87.79 ± 168.66	388.67 ± 442.21	73.19 ± 73.53
AST		24.91 ± 7.68	70.89 ± 112.36	362.19 ± 401.41	87.89 ± 177.25

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CHB: Chronic Hepatitis B virus; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; LC: Liver cirrhosis.

Table 2 Correlation of human leukocyte antigen-DP and human leukocyte antigen-DQ polymorphisms with the risk of chronic active hepatitis B, n (%)

SNPs	Healthy control	HBV carrier			Healthy control vs CHB		Healthy control vs HBV carrier
		CHB	HBV-related LC	HBV-related HCC	OR (95%CI)	P value	OR (95%CI)	P value
rs2856718
GG	106 (33.7)	173 (36.7)	100 (40.0)	87 (34.7)	1		1
AG	149 (47.3)	208 (44.2)	97 (38.8)	119 (47.4)	0.855 (0.621-1.179)	0.3392	0.838 (0.630-1.115)	0.2253
AA	60 (19.0)	90 (19.1)	53 (21.2)	45 (17.9)	0.919 (0.612-1.380)	0.6840	0.923 (0.642-1.326)	0.6631
AA + AG	209 (66.3)	298 (63.3)	150 (60.0)	164 (65.3)	0.874 (0.648-1.179)	0.3767	0.862 (0.660-1.127)	0.2774
G allele	361 (57.3)	554 (58.8)	297 (59.4)	293 (58.4)	1		1
A allele	269 (42.7)	384 (41.2)	203 (40.6)	209 (41.6)	0.930 (0.758-1.141)	0.4882	0.939 (0.782-1.126)	0.4937
rs3077
GG	133 (42.2)	246 (52.2)	128 (51.2)	152 (60.5)	1		1
AG	139 (44.1)	196 (41.6)	107 (42.8)	84 (33.5	0.762 (0.563-1.032)	0.0702	0.704 (0.537-0.924)	0.0113
AA	43 (13.7)	29 (6.2)	15 (6.0)	15 (6.0)	0.365 (0.218-0.611)	0.0001	0.347 (0.224-0.537)	< 0.0001
AA + AG	182 (57.8)	225 (47.8)	122 (48.8)	99 (39.5)	0.668 (0.501-0.891)	0.0060	0.620 (0.479-0.801)	0.0003
G allele	405 (64.3)	688 (73.0)	364 (72.5)	388 (77.3)	1		1
A allele	225 (35.7)	254 (27.0)	138 (27.5)	114 (22.7)	0.665 (0.535-0.826)	0.0002	0.632 (0.521-0.765)	< 0.0001
rs9277535
GG	159 (50.5)	275 (58.4)	142 (56.8)	154 (61.4)	1		1
AG	123 (39.0)	187 (39.7)	95 (38.0)	88 (35.0)	0.879 (0.651-1.186)	0.3993	0.838 (0.640-1.097)	0.1972
AA	33 (10.5)	9 (1.9)	13 (5.2)	9 (3.6)	0.158 (0.074-0.338)	< 0.0001	0.262 (0.155-0.440)	< 0.0001
AA + AG	156 (49.5)	196 (41.6)	108 (43.2)	97 (38.6)	0.726 (0.545-0.968)	0.0290	0.716 (0.555-0.924)	0.0102
G allele	441 (70.0)	737 (78.1)	379 (75.8)	396 (78.9)	1		1
A allele	189 (30.0)	205 (21.9)	121 (24.2)	106 (21.1)	0.649 (0.516-0.817)	0.0002	0.667 (0.545-0.815)	0.0001

CHB: Chronic Hepatitis B virus; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; LC: Liver cirrhosis.

Table 3 Correlation of human leukocyte antigen-DP and human leukocyte antigen-DQ polymorphisms with the risk of hepatitis B virus-related liver cirrhosis and hepatocellular carcinoma

SNPs	CHB vs HBV-related LC		CHB vs HBV-related HCC		HBV-related LC vs HBV-related HCC
	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
rs2856718
GG	1		1		1
AG	0.807 (0.572-1.139)	0.2219	1.138 (0.808-1.602)	0.4601	1.410 (0.952-2.089)	0.0865
AA	0.019 (0.670-1.549)	0.9307	1.006 (0.647-1.564)	0.9795	0.976 (0.598-1.594)	0.9224
AA + AG	0.871 (0.637-1.193)	0.3891	1.094 (0.794-1.508)	0.5813	1.257 (0.874-1.806)	0.2170
G allele	1		1		1
A allele	0.986 (0.791-1.230)	0.9011	1.029 (0.826-1.282)	0.7984	1.044 (0.811-1.342)	0.7396
rs3077
GG	1		1		1
AG	1.049 (0.763-1.442)	0.7673	0.694 (0.501-0.961)	0.0278	0.661 (0.457-0.957)	0.0284
AA	0.994 (0.514-1.921)	0.9859	0.837 (0.435-1.612)	0.5949	0.842 (0.397-1.789)	0.6548
AA + AG	1.042 (0.767-1.416)	0.7924	0.712 (0.522-0.972)	0.0324	0.683 (0.479-0.974)	0.0352
G allele	1		1		1
A allele	1.027 (0.805-1.310)	0.8305	0.791 (0.613-1.02)	0.0705	0.775 (0.582-1.032)	0.0810
rs9277535
GG	1		1		1
AG	0.984 (0.715-1.354)	0.9204	0.840 (0.610-1.159)	0.2883	0.854 (0.591-1.235)	0.4022
AA	2.797 (1.168-6.702)	0.0210	1.786 (0.694-4.593)	0.2290	0.638 (0.265-1.539)	0.3174
AA + AG	1.067 (0.783-1.455)	0.6814	0.884 (0.646-1.209)	0.4393	0.828 (0.580-1.183)	0.3001
G allele	1		1		1
A allele	1.148 (0.888-1.484)	0.2924	0.962 (0.739-1.254)	0.7759	0.838 (0.623-1.128)	0.2438

CHB: Chronic Hepatitis B virus; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; LC: Liver cirrhosis; SNP: Single nucleotide polymorphism.

Table 4 Pairwise linkage disequilibrum results

Hepatitis		rs3077	rs9277535	Cirrhosis		rs3077	rs9277535	HCC		rs3077	rs9277535	Healthy Control		rs3077	rs9277535
rs2856718	D	-0.038	-0.006	rs2856718	D	-0.032	-0.012	rs2856718	D	-0.028	-0.015	rs2856718	D	-0.041	-0.025
	D'	0.340	0.069		D'	0.288	0.117		D'	0.298	0.166		D'	0.272	0.198
	Corr.(R)	-0.173	-0.030		Corr.(R)	-0.146	-0.055		Corr.(R)	-0.136	-0.073		Corr.(R)	-0.175	-0.112
	R2	0.030	0.001		R2	0.021	0.003		R2	0.019	0.005		R2	0.031	0.013
	χ2	28.168	0.874		χ2	10.691	1.498		χ2	9.352	2.651		χ2	19.260	7.903
	P value	< 0.0001	0.350		P value	0.001	0.221		P value	0.002	0.103		P value	< 0.0001	0.005
	n	471	471		n	250	250		n	251	251		n	315	315
rs3077	D		0.072	rs3077	D		0.074	rs3077	D		0.066	rs3077	D		0.109
	D'		0.450		D'		0.419		D'		0.405		D'		0.565
	Corr.(R)		0.391		Corr.(R)		0.385		Corr.(R)		0.387		Corr.(R)		0.496
	R2		0.153		R2		0.148		R2		0.150		R2		0.246
	χ2		143.729		χ2		74.223		χ2		75.122		χ2		155.016
	P value		< 2.2 × 10-16		P value		< 2.2 × 10-16		P value		< 2.2 × 10-16		P value		< 2.2 × 10-16
	n		471		n		250		n		251		n		315

D: The coefficient of linkage disequilibrium. The coefficient of linkage disequilibrium D is not always a convenient measure of linkage disequilibrium because its range of possible values depends on the frequencies of the alleles it refers to. This makes it difficult to compare the level of linkage disequilibrium between different pairs of alleles. Lewontin suggested normalising D by dividing it by the theoretical maximum difference between the observed and expected haplotype frequencies as follows: D'= D/D_max where D_max = max{-P_AP_B, -(1-P_A)} when D < 0; where D_max = min{P_A(1-P_B), (1-P_A)P_B when D > 0. An alternative to D' is the correlation coefficient between pairs of loci, usually expressed as its square, R²: the correlation coefficient between pairs of loci. R² = D²/[P_A(1-P_A) P_B(1-P_B)]. The measures R² and D’ have limits to their ranges and do not range over all values of zero to one for all pairs of loci. The maximum of R² depends on the allele frequencies at the two loci being compared and can only range fully from zero to one where either the allele frequencies at both loci are equal, P_A = P_B when D > 0 or when the allele frequencies have the relationship P_A = 1-P_B when D < 0. While D’ can always take a maximum value of 1, its minimum value for two loci is equal to |R| for those loci. HCC: Hepatocellular carcinoma.

Table 5 Risk ratio of haplotype rs2856718-rs30277-rs9277535

Haplotype: Rs2856718, rs30277, rs9277535		A/G_A/G_A	A/G_A/G_A/	A/G_A/G_G	A/G_A_A	A/G_A_A/G	A/G_A_G	A/G_G_A	A/G_G_A/G	A/G_G_G	A_A/G_A	A_A/G_A/G	A_A/G_G	A_A_A	A_A_A/G	A_A_G	A_G_A	A_G_A/G	A_G_G	G_A/G_A	G_A/G_A/G	G_A/G_G	G_A_A	G_A_A/G	G_A_G	G_G_A	G_G_A/G	G_G_G
Hepatitis	N	2	51	30	NA	4	3	NA	35	83	1	17	11	1	2	1	NA	12	45	1	37	46	4	11	3	NA	18	53
	%	0.4	10.8	6.4	NA	0.8	0.6	NA	7.4	17.6	0.2	3.6	2.3	0.2	0.4	0.2	NA	2.5	9.6	0.2	7.9	9.8	0.8	2.3	0.6	NA	3.8	11.3
	Pfisher	1.15 × 10-01	3.89 × 10-01	3.24 ×10-01	1.53 × 10-02	2.96 × 10-01	3.78 × 10-01	1.52 × 10-01	2.85 × 10-01	1.95 × 10-01	5.00 × 10-01	1.54 × 10-01	4.27 × 10-01	2.12 × 10-01	5.00 × 10-01	5.00 × 10-01	2.68 × 10-01	2.83 × 10-01	3.86 × 10-01	8.36 × 10-02	3.38 × 10-01	1.47 × 10-02	1.59 × 10-01	4.24 × 10-01	5.00 × 10-01	5.00 × 10-01	3.19 × 10-01	3.60 × 10-01
	Pyates	1.27 × 10-01	4.18 ×10-01	3.18 × 10-01	2.62 × 10-02	2.97 × 10-01	3.71 × 10-01	1.58 × 10-01	3.30 × 10-01	2.05 × 10-01	5.00 × 10-01	1.88 × 10-01	4.69 × 10-01	2.77 × 10-01	5.00 × 10-01	5.00 × 10-01	3.67 × 10-01	3.65 × 10-01	3.97 × 10-01	1.06 × 10-01	3.64 × 10-01	1.78 × 10-02	1.91 × 10-01	5.00 × 10-01	5.00 × 10-01	5.00 × 10-01	3.73 × 10-01	3.76 × 10-01
	Puncor	7.49 × 10-02	3.82 × 10-01	2.79 × 10-01	1.11 × 10-02	2.11 × 10-01	2.60 × 10-01	6.40 × 10-02	2.90 × 10-01	1.83 × 10-01	3.15 × 10-01	1.45 × 10-01	3.96 ×10-01	1.55 × 10-01	4.34 × 10-01	3.47 × 10-01	1.41 × 10-01	2.94 × 10-01	3.61 × 10-01	5.56 × 10-02	3.25 × 10-01	1.35 × 10-02	1.30 × 10-01	4.40 × 10-01	4.79 × 10-01	2.24 × 10-01	3.15 × 10-01	3.42 × 10-01
	RR	0.45	1.04	0.92	NA	0.73	0.74	NA	1.08	1.09	0.68	1.23	0.94	0.45	0.91	1.37	NA	1.13	0.96	0.3	0.94	1.31	0.64	1.04	1.02	NA	1.1	0.95
	Lower	0.13	0.82	0.68	NA	0.31	0.28	NA	0.83	0.91	0.12	0.86	0.58	0.08	0.29	0.34	NA	0.73	0.75	0.05	0.72	1.05	0.27	0.65	0.42	NA	0.76	0.76
	Upper	1.61	1.3	1.24	NA	1.69	1.96	NA	1.41	1.31	3.73	1.77	1.52	2.72	2.83	5.48	NA	1.76	1.22	1.92	1.23	1.64	1.51	1.66	2.51	NA	1.58	1.2
HCC	N	2	23	18	1	3	2	2	20	48	NA	5	NA	NA	3	1	NA	5	31	2	18	16	1	3	1	1	8	37
	%	0.8	9.2	7.2	0.4	1.2	0.8	0.8	8	19.1	NA	2	NA	NA	1.2	0.4	NA	2	12.4	0.8	7.2	6.4	0.4	1.2	0.4	0.4	3.2	14.7
	Pfisher	5.00 × 10-01	2.46 × 10-01	4.45 × 10-01	5.00 × 10-01	5.00 × 10-01	5.00 × 10-01	8.65 × 10-02	2.44 × 10-01	1.08 × 10-01	5.00 × 10-01	2.04 × 10-01	6.15 × 10-04	3.02 × 10-01	4.62 × 10-02	1.76 × 10-01	5.00 × 10-01	5.00 × 10-01	7.96 × 10-02	3.45 × 10-01	2.63 × 10-01	2.53 × 10-01	1.10 × 10-01	1.70 × 10-01	5.00 × 10-01	9.75 × 10-02	5.00 × 10-01	5.09 × 10-02
	Pyates	5.00 × 10-01	2.58 × 10-01	4.84 × 10-01	4.15 × 10-01	5.00 × 10-01	5.00 × 10-01	1.81 × 10-01	2.76 × 10-01	1.14 × 10-01	3.62 × 10-01	2.14 × 10-01	4.75 × 10-03	2.44 × 10-01	8.48 × 10-02	4.22 × 10-01	5.00 × 10-01	4.71 × 10-01	9.65 × 10-02	5.00 × 10-01	2.73 × 10-01	2.44 × 10-01	1.32 × 10-01	1.53 × 10-01	4.79 × 10-01	2.21 × 10-01	4.58 × 10-01	6.16 × 10-02
	Puncor	4.02 × 10-01	2.22 × 10-01	4.29 × 10-01	2.62 × 10-01	4.81 × 10-01	4.56 × 10-01	6.16 × 10-02	2.32 × 10-01	9.65 × 10-02	1.62 × 10-01	1.58 × 10-01	2.40 × 10-03	1.13 × 10-01	2.94 × 10-02	1.38 × 10-01	2.43 × 10-01	3.78 × 10-01	7.79 × 10-02	4.18 × 10-01	2.32 × 10-01	2.05 × 10-01	7.68 × 10-02	1.04 × 10-01	3.08 × 10-01	2.11 × 10-02	3.83 × 10-01	4.94 × 10-02
	RR	0.85	0.86	1.04	0.57	1.03	0.93	2.58	1.17	1.21	NA	0.67	NA	NA	2.58	2.57	NA	0.88	1.28	1.14	0.85	0.83	0.3	0.52	0.64	5.14	0.91	1.3
	Lower	0.24	0.58	0.68	0.09	0.37	0.26	0.96	0.78	0.91	NA	0.29	NA	NA	1.15	0.64	NA	0.39	0.92	0.33	0.55	0.52	0.04	0.18	0.1	4.6	0.48	0.96
	Upper	3.04	1.27	1.6	3.62	2.84	3.28	6.91	1.74	1.59	NA	1.52	NA	NA	5.79	10.32	NA	1.97	1.77	3.89	1.32	1.31	2.01	1.54	4.01	5.75	1.72	1.76
Cirrhosis	N	1	21	19	1	2	1	1	17	36	2	9	9	1	NA	NA	1	6	24	2	22	20	4	6	1	NA	12	32
	%	0.4	8.4	7.6	0.4	0.8	0.4	0.4	6.8	14.4	0.8	3.6	3.6	0.4	NA	NA	0.4	2.4	9.6	0.8	8.8	8	1.6	2.4	0.4	NA	4.8	12.8
	Pfisher	2.40 × 10-01	1.26 × 10-01	3.38 × 10-01	5.00 × 10-01	3.74 × 10-01	3.51 × 10-01	2.89 × 10-01	5.00 × 10-01	1.96 × 10-01	8.59 × 10-02	2.66 × 10-01	1.27 × 10-01	5.00 × 10-01	3.02 × 10-01	5.00 × 10-01	1.75 × 10-01	4.07 × 10-01	4.53 × 10-01	3.45 × 10-01	3.99 × 10-01	3.95 × 10-01	3.78 × 10-01	4.07 × 10-01	5.00 × 10-01	5.00 × 10-01	1.24 × 10-01	2.92 × 10-01
	Pyates	2.71 × 10-01	1.39 × 10-01	3.68 ×10-01	4.17 ×10-01	3.93 × 10-01	3.13 × 10-01	5.00 ×10-01	5.00 × 10-01	1.97 × 10-01	1.80 × 10-01	3.21 × 10-01	1.51 × 10-01	5.00 × 10-01	2.46 × 10-01	5.00 × 10-01	4.21 × 10-01	5.00 × 10-01	4.66 × 10-01	5.00 × 10-01	4.28 × 10-01	4.51 × 10-01	4.51 × 10-01	5.00 × 10-01	4.81 × 10-01	5.00 × 10-01	1.45 × 10-01	3.17 × 10-01
	Puncor	1.65 × 10-01	1.15 × 10-01	3.17 × 10-01	2.63 × 10-01	2.74 × 10-01	1.92 × 10-01	3.89 × 10-01	4.68 × 10-01	1.71 × 10-01	6.08 × 10-02	2.50 × 10-01	1.04 × 10-01	4.32 ×10-01	1.14 × 10-01	2.44 × 10-01	1.37 × 10-01	4.31 × 10-01	4.19 × 10-01	4.16 × 10-01	3.78 × 10-01	3.99 × 10-01	3.33 × 10-01	4.31 × 10-01	3.10 × 10-01	3.12 × 10-01	1.06 × 10-01	2.80 × 10-01
	RR	0.43	0.78	1.11	0.57	0.68	0.47	1.29	0.98	0.86	2.59	1.23	1.46	0.86	NA	NA	2.58	1.07	0.96	1.15	1.06	1.06	1.21	1.07	0.64	NA	1.39	1.1
	Lower	0.07	0.52	0.73	0.09	0.19	0.07	0.24	0.63	0.62	0.96	0.69	0.83	0.14	NA	NA	0.64	0.52	0.66	0.34	0.72	0.7	0.51	0.52	0.1	NA	0.85	0.79
	Upper	2.8	1.18	1.68	3.63	2.5	3.03	7.06	1.53	1.18	6.94	2.2	2.58	5.15	NA	NA	10.36	2.19	1.4	3.91	1.57	1.59	2.88	2.19	4.03	NA	2.29	1.54
Healthy control	N	7	40	22	7	6	5	1	17	44	1	7	12	4	1	NA	1	6	28	4	30	16	8	9	3	NA	7	29
	%	2.2	12.7	7	2.2	1.9	1.6	0.3	5.4	14	0.3	2.2	3.8	1.3	0.3	NA	0.3	1.9	8.9	1.3	9.5	5.1	2.5	2.9	1	NA	2.2	9.2
	Pfisher	6.13 × 10-03	7.00 × 10-02	5.00 × 10-01	5.62 × 10-04	1.11 × 10-01	7.52 × 10-02	5.00 × 10-01	1.26 × 10-01	9.50 × 10-02	5.00 × 10-01	2.24 × 10-01	4.77 × 10-02	1.73 × 10-02	5.00 ×10-01	5.00 × 10-01	2.15 × 10-01	4.14 × 10-01	2.58 × 10-01	1.17 × 10-01	2.05 × 10-01	2.55 × 10-02	2.15 × 10-02	1.94 × 10-01	2.07 × 10-01	5.00 × 10-01	1.08 × 10-01	6.52 × 10-02
	Pyates	8.12 × 10-03	8.59 × 10-02	5.00 ×10-01	4.14 × 10-04	1.35 × 10-01	1.01 × 10-01	5.00 × 10-01	1.37 × 10-01	1.05 × 10-01	5.00 × 10-01	2.45 × 10-01	6.34 × 10-02	2.66 × 10-02	5.00 × 10-01	5.00 × 10-01	4.93 × 10-01	3.97 × 10-01	2.70 × 10-01	1.56 × 10-01	2.18 × 10-01	3.36 × 10-02	2.90 × 10-02	2.70 × 10-01	3.27 × 10-01	5.00 × 10-01	1.07 × 10-01	6.65 × 10-02
	Puncor	3.06 × 10-03	7.05 × 10-02	4.78 × 10-01	9.49 × 10-05	7.98 × 10-02	5.20 × 10-02	4.90 × 10-01	1.11 × 10-01	9.04 × 10-02	4.90 × 10-01	1.89 × 10-01	4.13 × 10-02	7.99 × 10-03	3.28 × 10-01	2.10 × 10-01	2.00 × 10-01	3.16 × 10-01	2.35 × 10-01	8.10 × 10-02	1.85 × 10-01	2.55 × 10-02	1.46 × 10-02	2.03 × 10-01	1.95 × 10-01	2.85 × 10-01	7.83 × 10-02	5.44 × 10-02
	RR	0.55	0.92	1.00	0.29	0.79	0.72	0.99	1.08	1.06	0.99	1.08	0.82	0.44	1.10	1.32	0.66	1.05	1.04	0.73	0.95	1.12	0.70	0.91	0.83	1.32	1.12	1.08
	Lower	0.28	0.82	0.88	0.09	0.52	0.42	0.56	0.97	0.98	0.56	0.93	0.63	0.14	0.77	1.28	0.17	0.87	0.94	0.41	0.84	1.02	0.45	0.71	0.48	1.28	0.99	0.99
	Upper	1.07	1.04	1.13	0.99	1.20	1.24	1.75	1.20	1.14	1.75	1.26	1.08	1.37	1.58	1.37	2.65	1.27	1.14	1.32	1.07	1.23	1.09	1.17	1.42	1.37	1.28	1.18

HCC: Hepatocellular carcinoma; RR: Risk ratio; NA: Not available.

Table 6 The risk ratio results of haplotype rs2856718-rs30277-rs9277535 following the preclinical factors

Preclinical factors	Groups	Female	Male	All
Total bilirubin (µmol/L); Normal range: < 17 µmol/L	Hepatitis	AG/GG/GG
		RR = 0.72 (0.49; 1.06)
		Cutpoint = 7.08 µmol/L
		Nupper/Nlower = 10/6
		Pfisher = 0.017, Pyates = 0.027, Puncor = 0.011
	HCC		AG/GG/GG
			RR = 1.45 (1.05; 1.99)
			Cutpoint = 43.6 µmol/L
			Nupper/Nlower = 25/19
			Pfisher = 0.02, Pyates= 0.03, Puncor = 0.02
AFP (IU/mL); Normal range: < 5.8 IU/mL	Hepatitis	AA/GG/GG
		RR = 0.44 (0.20; 0.99)
		Cutpoint = 33.11 U/mL
		Nupper/Nlower = 4/7
		Pfisher = 0.008, Pyates = 0.008, Puncor = 0.002
ALB (g/L); Normal range: 35-50 g/L	HCC			GG/AG/AG
				RR = 2.20 (1.24; 3.92)
				Cutpoint = 43.6 g/L
				Nupper/Nlower = 8/10
				Pfisher = 0.016, Pyates = 0.018, Puncor = 0.008
Direct bilirubin (µmol/L); Normal range: < 4.3 µmol/L	HCC			GG/AG/GG
				RR = 1.57 (1.09; 2.25)
				Cutpoint = 5.13 µmol/L
				Nupper/Nlower = 11/5
				Pfisher = 0.034, Pyates = 0.046, Puncor = 0.026
Tumor size (cm)	HCC			GG/AA/AG	AA/GG/AG
				RR = 2.2 (1.94; 2.56)	RR = 2.25 (1.96; 2.59)
				Cutpoint = 5 cm	Cutpoint = 5 cm
				Nupper/NloweRR = 5/0	Nupper/NloweRR = 3/0
				Pfisher = 0.009, Pyates = 0.02, Puncor = 0.006	Pfisher = 0.046, Pyates = 0.092, Puncor = 0.028
ALT (U/L); Normal range: < 40 U/L at 37 oC	HCC			GG/AG/AG
				RR = 0.74 (0.49; 1.13)
				Cutpoint = 28.8 U/L
				Nupper/Nlower = 10/8
				Pfisher = 0.048, Pyates = 0.068, Puncor = 0.038
AST (U/L); Normal range: < 37 U/L at 37 oC	HCC		GG/GG/GG	GG/GG/GG
			RR = 0.52 (0.25; 1.10)	RR = 0.53 (0.27; 1.06)
			Cutpoint = 58.9 U/L	Cutpoint = 58.9 U/L
			Nupper/Nlower = 6/26	Nupper/Nlower = 7/30
			Pfisher = 0.034, Pyates = 0.043, Puncor = 0.028	Pfisher = 0.029, Pyates = 0.036, Puncor = 0.024
Age (years old)	Hepatitis	GG/AG/AG
		RR = 0.63 (0.31; 1.28)
		Cutpoint = 31 years old
		Nupper/Nlower = 3/2
		Pfisher = 0.013, Pyates = 0.0086, Puncor = 0.0004
	Cirrhosis			AA/AG/AG
				RR = 0.38 (0.11; 1.31)
				Cutpoint = 52 years old
				Nupper/Nlower = 2/7
				Pfisher = 0.023, Pyates = 0.038, Puncor = 0.018
	HCC			GG/GG/GG
				RR = 1.63 (0.98; 2.71)
				Cutpoint = 63 years old
				Nupper/Nlower = 13/24
				Pfisher = 0.045, Pyates = 0.055, Puncor = 0.035
Gender (Female, male)	Hepatitis			AG/AG/GG
				RR = 0.76 (0.56; 1.02)
				Cutpoint = Male
				Nmale/Nfemale = 18/12
				Pfisher = 0.03, Pyates = 0.01, Puncor = 0.007
	HCC			AA/GG/GG		AG/AG/GG
				RR = 0.74 (0.567; 0.96)		RR = 1.20 (1.13; 1.27)
				Cutpoint = Male		Cutpoint = Male
				Nmale/Nfemale = 12/11		Nmale/Nfemale = 18/0
				Pfisher = 0.001, Pyates = 0.001, Puncor = 0.0005		Pfisher = 0.04, Pyates = 0.06, Puncor = 0.02
GGT (U/L); Male: 11-50 U/L at 37 oC; Female: 7-32 U/L at 37 oC	Cirrhosis			AG/GG/GG
				RR = 1.71 (1.09; 2.70)
				Cutpoint = 181.97 U/L
				Nupper/Nlower = 15/21
				Pfisher = 0.02, Pyates = 0.024, Puncor = 0.014

HCC: Hepatocellular carcinoma; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALB: Albumin; GGT: Gamma glutamyl transferase.