Liver histopathological lesions is severe in patients with normal alanine transaminase and low to moderate hepatitis B virus DNA replication

Table 1 Distribution of baseline characteristics in 634 chronic hepatitis B patients with alanine transaminase < upper limit of normal

Parameters	All patients (n = 634)	HBV DNA levels (EASL guidelines)				HBV DNA levels (CMA guidelines)
		Low/moderate replication (n = 336)	High replication (n = 298)	χ2/t /Z/u	P value	Low/moderate replication (n = 377)	High replication (n = 257)	χ2/t/Z/u	P value
Age, mean ± SD, yr	35.61 ± 10.30	38.09 ± 9.99	32.82 ± 9.95	6.640	< 0.001	37.34 ± 10.17	33.07 ± 9.99	5.222	< 0.001
Male, n (%)	349 (55.05)	192 (57.14)	157 (52.68)	1.269	0.260	209 (55.44)	140 (54.47)	0.057	0.811
HBeAg positive, n (%)	432 (68.14)	142 (42.26)	290 (97.31)	220.486	< 0.001	180 (47.74)	252 (98.05)	178.165	< 0.001
ALB, mean ± SD, g/L	42.72 ± 4.45	42.91 ± 4.97	42.49 ± 3.78	1.189	0.235	42.75 ± 4.88	42.67 ± 3.74	0.220	0.826
GLB, mean ± SD, g/L	27.82 ± 4.20	27.96 ± 4.11	27.66 ± 4.30	0.893	0.372	28.11 ± 4.19	27.40 ± 4.18	2.105	0.036
AGR, mean ± SD	1.57 ± 0.29	1.57 ± 0.30	1.57 ± 0.28	-0.148	0.882	1.56 ± 0.30	1.59 ± 0.28	-1.581	0.114
ALT, mean ± SD, U/L	23.77 ± 8.58	24.84 ± 8.66	22.56 ± 8.34	3.372	0.001	24.38 ± 8.69	22.87 ± 8.35	2.186	0.029
AST, mean ± SD, U/L	24.15 ± 8.91	25.00 ± 7.52	23.20 ± 10.18	2.558	0.011	25.04 ± 10.28	22.85 ± 6.17	3.069	0.002
ALP, mean ± SD, U/L	71.26 ± 26.06	71.52 ± 24.85	70.96 ± 27.39	0.269	0.788	71.21 ± 24.99	71.32 ± 27.60	-0.054	0.957
GGT, median (Q1-Q3), U/L	18.00 (13.00-25.00)	20.00 (15.00-30.00)	16.00 (13.00-23.00)	4.966	< 0.001	19.00 (14.00-29.00)	16.00 (13.00-23.00)	4.069	< 0.001
WBC count, mean ± SD, × 109/L	5.39 ± 1.42	5.33 ± 1.39	5.47 ± 1.45	-1.208	0.228	5.33 ± 1.44	5.48 ± 1.39	-1.321	0.187
NLR, mean ± SD	2.03 ± 1.24	2.05 ± 1.37	2.01 ± 1.08	0.443	0.658	2.04 ± 1.33	2.01 ± 1.09	0.298	0.766
PLT count, mean ± SD, × 109/L	175.67 ± 48.83	163.93 ± 47.39	188.90 ± 47.09	-6.641	< 0.001	166.86 ± 47.55	188.58 ± 47.90	-5.629	< 0.001
HBV DNA, mean ± SD, log IU/mL	6.18 ± 1.87	4.68 ± 1.26	7.88 ± 0.50	-41.111	< 0.001	4.95 ± 1.41	7.99 ± 0.44	-33.427	< 0.001
APRI, median (Q1–Q3)	0.33 (0.25-0.44)	0.36 (0.28-0.51)	0.29 (0.23-0.38)	6.936	< 0.001	0.36 (0.27-0.48)	0.30 (0.23-0.38)	5.725	< 0.001
FIB-4, median (Q1-Q3)	0.99 (0.69-1.38)	1.13 (0.83-1.61)	0.80 (0.58-1.13)	8.109	< 0.001	1.09 (0.79-1.56)	0.81 (0.59-1.13)	6.877	< 0.001
LIF-5, mean ± SD	0.40 ± 0.15	0.45 ± 0.15	0.36 ± 0.14	7.832	< 0.001	0.44 ± 0.15	0.35 ± 0.14	7.195	< 0.001
Liver inflammatory activity
A0, n (%)	117 (18.45)	58 (17.26)	59 (19.80)	4.189	< 0.001	61 (16.18)	56 (21.79)	4.426	< 0.001
A1, n (%)	381 (60.10)	174 (51.79)	207 (69.46)			206 (54.64)	175 (68.09)
A2, n (%)	97 (15.30)	73 (21.73)	24 (8.05)			78 (20.69)	19 (7.39)
A3, n (%)	39 (6.15)	31 (9.23)	8 (2.68)			32 (8.49)	7 (2.72)
≥ A2, n (%)	136 (21.45)	104 (30.95)	32 (10.74)	38.299	< 0.001	110 (29.18)	26 (10.12)	32.952	< 0.001
Liver fibrosis
F0, n (%)	148 (23.34)	61 (18.15)	87 (29.19)	6.382	< 0.001	70 (18.57)	78 (30.35)	6.053	< 0.001
F1, n (%)	332 (52.37)	153 (45.54)	179 (60.07)			179 (47.48)	153 (59.53)
F2, n (%)	87 (13.72)	65 (19.35)	22 (7.38)			70 (18.57)	17 (6.61)
F3, n (%)	37 (5.84)	29 (8.63)	8 (2.68)			30 (7.96)	7 (2.72)
F4, n (%)	30 (4.73)	28 (8.33)	2 (0.67)			28 (7.43)	2 (0.78)
≥ F2, n (%)	154 (24.29)	122 (36.31)	32 (10.74)	56.155	< 0.001	128 (33.95)	26 (10.12)	47.212	< 0.001
Treatment indication
< A2 and < F2, n (%)	442 (69.72)	191 (56.85)	251 (84.23)	56.089	< 0.001	224 (59.42)	218 (84.82)	46.730	< 0.001
≥ A2 or/and ≥ F2, n (%)	192 (30.28)	145 (43.15)	47 (15.77)			153 (40.58)	39 (15.18)

Quantitative data of normal distribution were expressed as mean ± standard deviation, non-normal distribution data were expressed as median (Q1-Q3), and categorical data were expressed as frequency and percentage. A: Liver inflammatory activity; AGR: Albumin–globulin ratio; ALB: Albumin; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; APRI: Aspartate transaminase to platelet ratio index, APRI = [(AST/ULN)/platelet counts (10⁹/L)] × 100[16]; AST: Aspartate aminotransferase; CMA: Chinese Medical Association; EASL: European Association for the Study of the Liver; F: Liver fibrosis; GLB: Globulin; FIB-4: Fibrosis-4, FIB-4 = [age (year) × AST (U/L)]/(platelet count (10⁹/L) × [ALT (U/L)^1/2][17]; GGT: Gamma-glutamyl transpeptidase; HBeAg: Hepatitis B e antigen; LIF-5: Liver inflammation and fibrosis-5, LIF-5 = 0.725 + 0.005 × age (year) + 0.003 × ALT (U/L) + 0.004 × AST (U/L) - 0.201 × (A/G) - 0.002 × PLT (10⁹/L)[18]; NLR: Neutrophils lymphocytes ratio; PLT: Platelets; WBC: White blood cell.