Peripheral T-lymphocyte subpopulations in different clinical stages of chronic HBV infection correlate with HBV load

Table 1 Characteristics of patients with chronic HBV infection (mean ± SD), n (%)

Characteristics	Patients (n = 422)	Clinical stage of chronic HBV infection
		Tolerant (n = 112)	Active (n = 222)	Inactive carrier (n = 88)	P
Sex (Male/female)	268/154	67/45	156/66	45/43	< 0.051
Mean age (yr)	30.59 ± 10.40	29.45 ± 11.72	29.69 ± 9.30	34.34 ± 10.53	< 0.0012
Patients with MH	233 (55.2)	93 (83.0)	115 (51.8)	25 (28.4)	< 0.0011
Age at HBV-infection (yr)					< 0.0011
< 8	166 (39.3)	62 (55.4)	92 (41.4)	12 (13.6)
8-20	127 (30.1)	33 (29.5)	80 (36.0)	14 (15.9)
> 20	103 (24.4)	9 (8.0)	46 (20.7)	48 (54.5)
Unknown	26 (6.2)	8 (6.3)	4 (1.8)	14 (15.9)
Serum ALT (IU/L)	116.52 ± 82.66	25.37 ± 12.56	161.42 ± 139.26	31.15 ± 19.67	< 0.0012
Serum AST (IU/L)	82.61 ± 79.89	22.20 ± 14.63	116.63 ± 107.84	25.29 ± 12.52	< 0.0012
Serum TBIL (&mgr;mol/mL)	15.66 ± 9.22	15.08 ± 2.55	20.78 ± 14.25	13.55 ± 11.24	< 0.0012
HBV DNA positive	285 (67.5)	112(100)	165 (74.3)	8 (9.1)	< 0.0011
Serum HBV DNA (copies/mL)					< 0.0011
≤ 1.0 × 103	137 (32.5)	0	57 (25.7)	80 (90.9)
> 1.0 × 103-1.0 × 105	46 (10.9)	6 (5.4)	32 (14.4)	8 (9.1)
> 1.0 × 105-1.0 × 107	60 (14.2)	22 (19.6)	38 (17.1)	0
> 1.0 × 107	179 (42.4)	84 (75.0)	95 (42.8)	0
HBV DNA (Log, copies/mL)	5.87 ± 2.43	7.88 ± 1.54	5.94 ± 2.21	3.11 ± 0.37	< 0.0012
HBeAg positive	218 (51.7)	112 (100)	96 (43.2)	10 (11.4)	< 0.0011
HBV pre-C region mutation positive	122 (28.9)	37 (33.0)	71 (32.0)	14 (15.9)	< 0.011

¹χ² test;

²ANOVA. HBV: Hepatitis B virus; MH: Maternal HBV-infection status.

Table 2 Characteristics of chronic HBV infection patients at the immune-tolerant and immune-active stages (mean ± SD), n (%)

Characteristics	Immune-tolerant stage (n = 112)			Immune-active stage (n = 222)
	HBV DNA (< 1.0 × 107 copies/mL) (n = 28)	HBV DNA (> 1.0 × 107 copies/mL) (n = 84)	P	HBV DNA (< 1.0 × 107 copies/mL) (n = 127)	HBV DNA (> 1.0 × 107 copies/mL) (n = 95)	P
Sex (Male/female)	13/15	54/30	> 0.051	87/40	69/26	> 0.051
Mean age (yr)	30.80 ± 10.20	30.61 ± 10.90	> 0.052	31.17 ± 9.82	27.71 ± 8.18	< 0.012
Patients with MH	16 (57.1)	77 (91.7)	< 0.0011	48 (37.8)	67 (70.5)	< 0.0011
Age at HBV-infection (yr)			> 0.051			< 0.0011
< 8	14 (50.0)	48 (54.8)		34 (26.8)	58 (61.0)
8-20	10 (35.7)	23 (31.2)		54 (42.5)	26 (27.4)
> 20	2 (7.1)	7 (7.5)		38 (29.9)	8 (8.4)
Unknown	2 (7.1)	6 (6.5)		1 (0.8)	3 (3.2)
Serum ALT (IU/L)	25.32 ± 12.6	29.54 ± 11.28	> 0.052	111.36 ± 86.5	211.33 ± 173.20	< 0.0012
Serum AST (IU/L)	24.54 ± 16.33	24.59 ± 18.31	> 0.052	79.08 ± 60.87	151.84 ± 136.65	< 0.0012
Serum total bilirubin (&mgr;mol /mL)	12.55 ± 6.28	11.83 ± 8.59	> 0.052	17.68 ± 8.28	23.80 ± 17.97	< 0.0012
HBV DNA positive	28 (100)	84 (100)	> 0.051	70 (55.1)	95 (100)	< 0.0011
HBV DNA (Log, copies/mL)	5.62 ± 0.81	8.63 ± 0.82	< 0.0012	4.31 ± 1.36	8.13 ± 0.74	< 0.0012
HBeAg positive	28 (100.0)	84 (100.0)	> 0.051	30 (23.6)	66 (69.5)	< 0.0011
HBV pre-C region mutation positive	1 (3.6)	36 (42.9)	< 0.0011	29 (22.8)	42 (44.2)	< 0.011

¹χ² test;

²t-test.

Table 3 Peripheral T-cell subsets broken down by various factors in normal controls and chronic HBV infection patients (mean ± SD)

Groups	Patients (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	422	56.42 ± 13.16	31.97 ± 7.30	33.73 ± 8.63	1.04 ± 0.45
Clinical stages of HBV infectionc
Tolerant	112	50.78 ± 13.26	30.23 ± 6.35	36.87 ± 7.58	0.86 ± 0.29
Active	222	55.51 ± 12.50	30.92 ± 7.40	34.37 ± 9.07	1.00 ± 0.47
Inactive carrier	88	65.89 ± 9.09	36.85 ± 6.06	28.09 ± 5.64	1.37 ± 0.39
HBV DNA loads (copies/mL)d
≤ 1.0 × 103	137	65.96 ± 8.58	37.45 ± 6.14	26.89 ± 5.71	1.46 ± 0.42
> 1.0 × 103-1.0 × 105	46	62.28 ± 7.50	33.33 ± 5.61	31.81 ± 5.95	1.10 ± 0.36
> 1.0 × 105-1.0 × 107	60	60.05 ± 12.97	31.58 ± 6.99	33.83 ± 7.50	0.97 ± 0.26
> 1.0 × 107	179	46.39 ± 9.93	27.56 ± 5.49	39.41 ± 7.36	0.73 ± 0.23
HBeAg statusb
Negative	204	62.62 ± 10.67	34.83 ± 7.16	29.66 ± 7.35	1.27 ± 0.48
Positive	218	50.61 ± 12.62	29.29 ± 6.37	37.53 ± 7.98	0.83 ± 0.29
HBV pre-C region mutation statusb
Negative	300	58.40 ± 12.89	33.63 ± 6.94	31.73 ± 8.04	1.15 ± 0.44
Positive	122	51.55 ± 12.57	27.89 ± 6.56	38.63 ± 8.06	0.78 ± 0.37
Maternal HBV-infection statusb
Negative	189	62.34 ± 10.89	35.31 ± 6.32	29.64 ± 6.87	1.27 ± 0.43
Positive	233	51.61 ± 12.89	29.27 ± 6.93	37.04 ± 8.49	0.85 ± 0.37
Age at HBV infectionc (yr)
< 8	166	51.83 ± 12.86	28.17 ± 6.61	37.31 ± 8.16	0.80 ± 0.29
8-20	127	57.17 ± 12.27	33.05 ± 5.90	33.39 ± 7.91	1.07 ± 0.41
> 20	103	61.42 ± 11.89	36.02 ± 7.27	28.86 ± 7.89	1.35 ± 0.49
Unknown	26	62.25 ± 14.39	34.93 ± 6.34	31.78 ± 7.58	1.19 ± 0.45

Effects of various independent demographic, clinical and serological variables on T-cell profile of HBsAg positive individuals were analyzed.

^bP < 0.001 vs measurement of each T-cell parameter;

^cP < 0.01,

^dP < 0.001 vs ANOVA linear trend test.

Table 4 Multiple linear regression predicting peripheral blood T lymphocyte subpopulations (n = 422)

	CD3+ T lymphocytes			CD4+ T lymphocytes			CD8+ T lymphocytes			CD4+/CD8+ ratio
	β	SE	P	β	SE	P	β	SE	P	β	SE	P
Intercept	85.35	2.64		43.32	1.53		16.48	1.73		1.89	0.08
Serum HBV load (Log, copies/mL)1	-3.62	0.34	< 0.0001	-1.29	0.19	< 0.0001	1.80	0.22	< 0.0001	-0.1	0.01	< 0.0001
HBeAg2	-2.74	1.40	0.06	-1.95	0.81	0.01	3.42	0.92	< 0.001	-0.16	0.04	< 0.01
HBV pre-C region mutation3	-0.67	1.13	0.55	-2.79	0.66	< 0.0001	3.38	0.74	< 0.0001	-0.15	0.04	< 0.0001
Clinical stages of HBV infection4			0.014			< 0.0001			< 0.001			< 0.0001
Active	-4.19	1.34		-3.64	0.77		3.63	0.88		-0.19	0.04
Inactive carrier	-5.17	1.98		-3.55	1.15		4.93	1.30		-0.26	0.06
Age at HBV infection5 (yr)			0.038			< 0.001			0.37			< 0.001
8-20	-1.07	1.25		2.21	0.73		0.14	0.82		0.07	0.04
> 20	-3.55	1.49		2.35	0.86		-0.55	0.98		0.15	0.05
Unknown	2.51	2.17		3.18	1.25		-0.94	1.42		0.16	0.07
Maternal HBV infection status6	-3.23	1.21	< 0.01	-1.35	0.70	0.06	2.14	0.79	< 0.01	-0.08	0.04	0.03

The linear regression model was employed in multivariate analysis to assess the independent effects of variables on peripheral blood T lymphocyte subpopulation. β: Coefficients from the model; SE: Standard error;

¹Continuous variable;

²Reference group with positive HBeAg;

³Reference group without pre-C mutation;

⁴Reference group at tolerant stage;

⁵Reference group with the age < 8 years at HBV infection;

⁶Reference group without maternal HBV infection status.