Thyroid hormone, immunoglobin and complements for predicting hepatocellular carcinoma development in patients with hepatitis B virus-related liver cirrhosis

Table 1 Characteristics of patients with hepatitis B virus-related liver cirrhosis (training set)

Variables	Patients did not develope HCC (n = 123)	Patients developed HCC (n = 19)	Z or χ²	P value
Age (years)	50 (45, 61)	62 (55, 67)	3.622	< 0.01
Male	80 (65)	14 (73.7)	0.549	0.46
Decompensated cirrhosis	54 (43.9)	16 (84.2)	10.698	< 0.01
Diabetes	39 (31.7)	11 (57.9)	4.947	0.03
Alanine transaminase (U/L)	33 (21, 67)	28 (21, 53)	0.947	0.34
Aspartate transaminase (U/L)	33 (24, 54)	37 (27, 47)	0.258	0.80
Gamma-glutamyl transpeptidase (U/L)	56 (26, 82)	60 (26, 152)	0.665	0.51
Total bilirubin (µmol/L)	22.5 (15.7, 31.6)	24 (16.5, 28.4)	0.012	0.99
Albumin (g/L)	39.9 (32, 43.3)	40 (32.2, 44.9)	0.515	0.61
Creatinine (µmol/L)	77.3 (68.4, 89.9)	82.4 (69.1, 93.5)	0.809	0.42
International normalized ratio	1.1 (1.0, 1.3)	1.1 (1.0, 1.3)	0.254	0.80
Platelet (E+09/L)	99 (63, 145)	81 (56, 105)	1.840	0.07
Total triiodothyronine (nmol/L)	1.5 (1.2, 1.8)	1.4 (1.2, 1.6)	1.319	0.19
Total tetraiodothyronine (nmol/L)	112 (93.1, 127.8)	109.9 (95.5, 131.1)	0.088	0.93
Free triiodothyronine (pmol/L)	4.7 (4.1, 5.3)	4.6 (4.0, 5.2)	0.896	0.37
Free tetraiodothyronine (pmol/L)	11.3 (9.8, 12.5)	11.5 (9.1, 12.8)	0.084	0.93
Thyroid-stimulating hormone (μIU/mL)	1.5 (1.0, 2.0)	1.3 (0.9, 2.5)	0.285	0.78
Duration of follow-up (months)	33 (28, 38)	21 (14, 27)	4.825	< 0.01

Comparison was conducted by a Mann-Whitney U test (median and interquartile range) for continuous variables, and χ² test for categorial values. HCC: Hepatocellular carcinoma.

Table 2 Characteristics of patients with hepatitis B virus-related liver cirrhosis (internal subgroup)

Variables	Patients did not develope HCC (n = 88)	Patients developed HCC (n = 12)	Z or χ²	P value
Age (years)	50.5 (46, 61.8)	63 (55, 67.8)	3.010	< 0.01
Male	58 (65.9)	9 (75.0)	0.395	0.75
Decompensated cirrhosis	30 (34.1)	10 (83.3)	10.669	< 0.01
Diabetes	22 (25)	6 (50)	3.274	0.09
Alanine transaminase (U/L)	35 (21, 68.8)	28.5 (18.8, 54.5)	0.960	0.34
Aspartate transaminase (U/L)	36 (25, 57.8)	43.5 (33, 54.5)	0.642	0.52
Gamma-glutamyl transpeptidase (U/L)	60 (28.3, 90)	130.5 (28.5, 169.8)	1.681	0.09
Total bilirubin (µmol/L)	21.8 (15.6, 30.7)	24.5 (16.9, 32.2)	0.536	0.59
Albumin (g/L)	40.3 (33.8, 43.9)	40.2 (33.2, 44.3)	0.042	0.97
Creatinine (µmol/L)	77.4 (70.1, 88.9)	81.3 (63.2, 90.8)	0.127	0.90
International normalized ratio	1.1 (1.0, 1.2)	1.1 (0.9, 1.2)	0.244	0.81
Platelet (E+09/L)	103.5 (65.5, 142.8)	74 (51.5, 90)	2.127	0.03
Total triiodothyronine (nmol/L)	1.6 (1.3, 1.9)	1.5 (1.3, 1.7)	1.008	0.31
Total tetraiodothyronine (nmol/L)	118.2 (102.5, 134.3)	113.2 (94.4, 135.5)	0.525	0.60
Free triiodothyronine (pmol/L)	4.8 (4.3, 5.3)	4.9 (4.3, 5.5)	0.106	0.92
Free tetraiodothyronine (pmol/L)	11.2 (9.8, 12.4)	12.2 (9.6, 13.1)	0.981	0.33
Thyroid-stimulating hormone (μIU/mL)	1.4 (1.1, 2.0)	1.3 (1.0, 2.6)	0.377	0.71
IgM (g/L)	1.4 (0.9, 1.8)	1.2 (1.0, 1.9)	0.048	0.96
IgA (g/L)	2.8 (2.2, 3.8)	2.8 (1.9, 4.1)	0.191	0.85
IgG (g/L)	14.9 (12.9, 18.8)	15.5 (11.1, 19.3)	0.472	0.64
Complement C3 (g/L)	0.8 (0.7, 0.9)	0.8 (0.6, 1.0)	0.074	0.94
Complement C4 (g/L)	0.2 (0.1, 0.2)	0.2 (0.1, 0.2)	0.871	0.38
Duration of follow-up (months)	32 (26.3, 36.8)	21.5 (12.5, 26.3)	3.759	< 0.01

Comparison was conducted by a Mann-Whitney U test (median and interquartile range) for continuous variables, and χ² test for categorial values. HCC: Hepatocellular carcinoma; Ig: Immunoglobulin.

Table 3 Characteristics of patients in the internal subgroup

Variables	Compensated cirrhosis (n = 60)	Decompensated cirrhosis (n = 40)	Z or χ²	P value
Age (years)	50.1 (45.3, 55)	60.2 (55, 66.8)	4.247	< 0.01
Male	38 (63.3)	29 (72.5)	0.912	0.34
Hepatocellular carcinoma	2 (3.3)	10 (25)	10.669	< 0.01
Diabetes	12 (20)	16 (40)	4.762	0.03
Alanine transaminase (U/L)	105.5 (21, 95.3)	52.1 (21.3, 59.5)	1.116	0.27
Aspartate transaminase (U/L)	71.3 (23.3, 56.5)	57.5 (29.5, 57.3)	1.165	0.24
Gamma-glutamyl transpeptidase (U/L)	74.2 (26.3, 82)	92.4 (35.5, 123)	1.530	0.13
Total bilirubin (µmol/L)	21 (14.9, 23.7)	35.3 (18.7, 47.7)	3.912	< 0.01
Albumin (g/L)	41.9 (39.8, 45.1)	34.3 (29.5, 40.1)	5.717	< 0.01
Creatinine (µmol/L)	79.4 (71.4, 89.5)	87.4 (66.8, 88.7)	0.310	0.76
International normalized ratio	1.1 (0.99, 1.1)	1.3 (1.1, 1.5)	5.365	< 0.01
Platelet (E+09/L)	122.1 (84.5, 153.5)	87.2 (50.3, 107.8)	3.652	< 0.01
Total triiodothyronine (nmol/L)	1.8 (1.6, 2.0)	1.3 (1.1, 1.5)	6.414	< 0.01
Total tetraiodothyronine (nmol/L)	125.3 (107.6, 140.8)	108.3 (90.9, 126.5)	2.698	< 0.01
Free triiodothyronine (pmol/L)	5.1 (4.6, 5.5)	4.3 (3.8, 4.9)	4.655	< 0.01
Free tetraiodothyronine (pmol/L)	11.3 (10.3, 12.3)	11.3 (9.6, 12.8)	0.127	0.90
Thyroid-stimulating hormone (μIU/mL)	1.6 (1.1, 1.9)	1.8 (1.1, 2.2)	0.454	0.65
IgM (g/L)	1.4 (0.9, 1.7)	1.6 (1.0, 2.0)	1.168	0.24
IgA (g/L)	2.6 (2.0, 3.1)	3.9 (2.6, 5.1)	4.208	< 0.01
IgG (g/L)	15.0 (12.3, 16.5)	17.4 (13.9, 19.8)	2.712	< 0.01
Complement C3 (g/L)	0.9 (0.7, 0.9)	0.7 (0.6, 1.0)	3.087	< 0.01
Complement C4 (g/L)	0.2 (0.1, 0.3)	0.1 (0.1, 0.2)	2.915	< 0.01
Duration of follow-up (months)	32 (25.3, 36.8)	27.9 (23, 35)	1.972	0.05

Comparison was conducted by a Mann-Whitney U test (median and interquartile range) for continuous variables, and χ² test for categorial values. Ig: Immunoglobulin.

Table 4 Risk factors for hepatocellular carcinoma in patients with liver cirrhosis (training set)

Baseline variables	Univariate			Multivariate
	OR	95%CI	P value	OR	95%CI	P value
Age (years)	1.081	1.029-1.135	< 0.01	1.068	1.014-1.125	0.01
Male	0.664	0.224-1.969	0.46
Decompensated cirrhosis	6.815	1.888-24.597	< 0.01	4.703	1.180-18.745	0.03
Diabetes	2.962	1.104-7.944	0.03
Alanine transaminase (U/L)	0.991	0.978-1.004	0.18
Gamma-glutamyl transpeptidase (U/L)	1.005	0.999-1.011	0.08	1.007	1.001-1.014	0.03
Total bilirubin (µmol/L)	1.007	0.982-1.033	0.57
International normalized ratio	0.746	0.081-6.888	0.80
Platelet (E+09/L)	0.990	0.979-1.000	0.05
Total triiodothyronine (nmol/L)	0.395	0.120-1.298	0.13
Total tetraiodothyronine (nmol/L)	0.997	0.980-1.014	0.73
Free triiodothyronine (pmol/L)	0.738	0.423-1.290	0.29
Free tetraiodothyronine (pmol/L)	0.949	0.749-1.203	0.67
Thyroid-stimulating hormone (μIU/mL)	1.101	0.683-1.776	0.69

OR: Odds ratio.

Table 5 Risk factors for hepatocellular carcinoma in patients with liver cirrhosis (internal subgroup)

Baseline variables	Univariate			Multivariate
	95%CI	P value	95%CI	P value	95%CI	P value
Age (years)	1.088	1.022-1.158	< 0.01	1.08	1.002-1.163	0.04
Male	1.552	0.391-6.162	0.53
Decompensated cirrhosis	9.667	1.989-46.972	< 0.01	5.476	0.906-33.101	0.06
Diabetes	3	0.877-10.265	0.08
Alanine transaminase (U/L)	0.992	0.978-1.006	0.26
Gamma-glutamyl transpeptidase (U/L)	1.007	1.001-1.014	0.03	1.01	1.002-1.019	0.01
Total bilirubin (µmol/L)	1.003	0.969-1.038	0.87
International normalized ratio	0.248	0.008-7.998	0.43
Platelet (E+09/L)	0.985	0.971-1.000	0.04
Total triiodothyronine (nmol/L)	0.519	0.113-2.384	0.4
Total tetraiodothyronine (nmol/L)	0.994	0.973-1.015	0.55
Free triiodothyronine (pmol/L)	1.008	0.472-2.152	0.98
Free tetraiodothyronine (pmol/L)	1.102	0.807-1.505	0.54
Thyroid-stimulating hormone (μIU/mL)	1.173	0.670-2.055	0.58
IgM (g/L)	1.574	0.792-3.126	0.2
IgA (g/L)	0.986	0.638-1.522	0.95
IgG (g/L)	0.96	0.834-1.105	0.57
Complement 3 (g/L)	1.588	0.081-31.080	0.76
Complement 4 (g/L)	0.096	0-462.908	0.59

Ig: Immunoglobulin; OR: Odds ratio.