Effect of viral load on T-lymphocyte failure in patients with chronic hepatitis B

Table 1 Characteristics of patients with chronic hepatitis B

Characteristics	All patients	Various courses of chronic hepatitis B
	(n = 206)	Mild-CHB (n = 101)	Moderate-CHB (n = 54)	Severe-CHB (n = 51)	P value
Sex (male/female)	143/63	68/33	36/18	39/12	> 0.052
Mean age (yr)1	29.61 ± 9.38	29.06 ± 9.88	29.72 ± 9.16	30.59 ± 8.67	> 0.053
Patients with MH, n (%)	104 (50.5)	45 (44.6)	23 (42.6)	36 (70.6)	< 0.012
Age at HBV-infection (yr), n (%)					< 0.012
< 8	86 (41.7)	34 (33.7)	22 (40.7)	30 (58.8)
8-20	71 (34.5)	39 (38.6)	22 (40.7)	10 (19.6)
> 20	45 (21.8)	28 (27.7)	8 (14.8)	9 (3.9)
unknown	4 (1.9)	0	2 (3.7)	2 (3.9)
Serum ALT (IU/L)1	163.75 ± 140.41	69.91 ± 17.36	152.04 ± 19.62	379.65 ± 186.44	< 0.0013
Serum AST (IU/L)1	116.69 ± 107.97	52.61 ± 14.13	96.26 ± 21.27	265.25 ± 125.12	< 0.0013
Serum total bilirubin (&mgr;mol/mL)1	20.79 ± 14.02	15.18 ± 2.42	19.20 ± 4.51	33.59 ± 23.22	< 0.0013
HBV DNA positive, n (%)	149 (72.3)	51 (50.5)	47 (87.0)	51 (100.0)	< 0.0012
Serum HBV DNA (copies/mL), n (%)					< 0.0012
≤ 1.0 × 103	57 (27.7)	50 (49.5)	7 (13.0)	0
> 1.0 × 103-1.0 × 105	32 (15.5)	14 (13.9)	18 (33.3)	0
> 1.0 × 105-1.0 × 107	31 (15.0)	11 (10.9)	11 (20.4)	9 (17.6)
> 1.0 × 107	86 (41.7)	26 (25.7)	18 (33.3)	42 (82.4)
HBV DNA load (Log, copies/mL)1	5.84 ± 2.22	4.77 ± 2.11	5.91 ± 1.83	7.91 ± 1.17	< 0.0013
HBeAg positive, n (%)	96 (46.6)	25 (24.8)	31 (57.4)	40 (78.4)	< 0.0012

HBV: Hepatitis B virus; CHB: Chronic hepatitis B; MH: Maternal HBV-infection status.

¹Date are expressed as mean ± SD;

²Chi-square test P-value;

³ANOVA P-value.

Table 2 Peripheral T-cell subsets in normal control and CHB patients broken down by various factors (mean ± SD)

Groups	n	CD3+	CD4+	CD8+	CD4+/CD8+ ratio
HBV statusb
Negative (normal control)	100	71.07 ± 4.76	38.94 ± 3.39	24.02 ± 4.35	1.67 ± 0.33
Positive	206	55.44 ± 12.39	30.92 ± 7.48	34.39 ± 9.22	1.01 ± 0.49
Maternal HBV-infection statusb
Negative	102	60.36 ± 10.68	34.92 ± 6.52	30.43 ± 7.76	1.25 ± 0.49
Positive	104	50.60 ± 12.09	26.99 ± 6.18	38.29 ± 8.91	0.77 ± 0.34
Age at HBV-infection (yr)d
< 8	86	49.83 ± 11.64	25.74 ± 5.16	39.11 ± 8.68	0.70 ± 0.24
8-20	71	59.28 ± 11.47	34.15 ± 6.31	31.49 ± 7.52	1.18 ± 0.47
> 20	45	60.29 ± 11.13	35.58 ± 7.27	29.68 ± 8.80	1.33 ± 0.54
Unknown	4	53.20 ± 12.45	32.63 ± 4.43	37.78 ± 5.54	0.88 ± 0.19
Liver diseases statusd
Mild-CHB	101	60.38 ± 11.51	33.57 ± 8.36	30.29 ± 8.91	1.23 ± 0.54
Moderate-CHB	54	56.69 ± 10.27	30.53 ± 4.79	35.26 ± 7.72	0.93 ± 0.31
Severe-CHB	51	44.32 ± 8.71	26.08 ± 5.19	41.63 ± 6.18	0.65 ± 0.19
HBV DNA load (copies/mL)f
≤ 1.0 × 103	57	66.13 ± 7.38	37.92 ± 5.94	25.18 ± 5.39	1.58 ± 0.43
> 1.0 × 103-1.0 × 105	32	60.93 ± 8.02	32.73 ± 6.42	33.18 ± 5.36	1.03 ± 0.33
> 1.0 × 105-1.0 × 107	31	54.28 ± 12.91	29.63 ± 7.07	35.17 ± 8.18	0.88 ± 0.25
> 1.0 × 107	86	46.72 ± 9.31	26.07 ± 4.52	40.69 ± 7.35	0.67 ± 0.22
HBeAg statusb
Negative	110	61.09 ± 10.67	33.99 ± 7.48	30.17 ± 8.04	1.24 ± 0.52
Positive	96	48.99 ± 11.06	27.39 ± 5.75	39.24 ± 8.05	0.73 ± 0.25

^bP < 0.001 for all comparisons of +ve vs -ve for each measure and each T-cell parameter;

^dP < 0.01,

^fP < 0.001 for ANOVA Linear trend test.

Table 3 Multiple linear regression predicting peripheral blood T lymphocyte subpopulations (n = 206)

	CD3+ T lymphocyte			CD4+ T lymphocyte			CD8+ T lymphocyte			CD4+/CD8+ ratio
	β	SE	P value	β	SE	P value	β	SE	P value	β	SE	P value
Intercept	69.39	3.51		35.6	2.07		23.21	2.56		1.55	0.12
Serum HBV load (Log, copies/mL)1	-2.58	0.45	< 0.0001	-1.31	0.26	< 0.0001	2.05	0.33	< 0.0001	-0.11	0.02	< 0.0001
HBeAg2	2.37	1.65	0.15	0.71	0.98	0.47	-1.16	1.21	0.34	0.06	0.06	0.32
Liver diseases status3			< 0.01			0.63			0.04			0.04
Moderate-CHB	-0.36	1.58		-1.15	0.93		2.34	1.15		-0.15	0.05
Severe-CHB	-6.14	1.88		-1.65	1.11		3.52	1.37		-0.14	0.06
Age at HBV-infection (yr)4			0.31			< 0.001			0.06			< 0.001
8-20	-0.06	2.09		4.1	1.24		-0.72	1.52		0.13	0.07
> 20	-1.72	2.55		4.03	1.51		-0.16	1.86		0.15	0.09
Unknown	1.93	4.94		6.17	2.92		-0.52	3.61		0.14	0.17
Maternal HBV-infection status5	3.61	2.05	0.08	1.78	1.21	0.14	-2.76	1.49	0.07	0.14	0.07	0.05

β: Coefficients from the model.

¹Continuous variable;

²Reference group: HBeAg-negative;

³Reference group: mild-CHB;

⁴Reference group: < 8 yr old age at HBV infection;

⁵Reference group: With maternal HBV-infection status.