乙型肝炎病毒在不同丙氨酸氨基转移酶状态下对Th17、Treg细胞及其比率的影响

doi:10.19723/j.issn.1671-167X.2022.02.012

Abstract

Abstract:

Objective: To evaluate the effects of hepatitis B virus (HBV) on helper T lymphocytes 17 (Th17), regulatory T lymphocyte (Treg) and Th17/Treg ratio in chronic hepatitis B patients in different alanine aminetransferase (ALT) stages. Methods: In the study, 336 chronic hepatitis B patients in the first hospital of Lanzhou University were analyzed. The hepatitis B antigen antibody parameters were measured by chemiluminescence immunoassay analyzer, the liver function parameters were measured by automatic biochemical analyzer, the HBV loads were measured by quantitative PCR, Th17, Treg and Th17/Treg ratios were detected by flow cytometry. Among them, 111 cases (ALT<40 U/L) of ALT were normal hepatitis B, 108 cases of chronic hepatitis B with ALT above normal upper limit and <2 times higher (40 U/L≤ALT<80 U/L), and 117 cases of chronic hepatitis B with ALT above 2 times normal upper limit (80 U/L≤ALT). According to the viral load, they were divided into low replication group with HBV DNA < 4.0 lg copies/mL, medium replication group with 4.0 lg copies/mL≤HBV DNA<6.0 lg copies/mL and high replication group with HBV DNA ≥ 6.0 lg copies / mL. Dunnett T3 variance analysis were used to analyze the effects of HBV on Th17, Treg and Th17/Treg ratio in the chronic hepatitis B patients in different ALT stages. The changes of virological and immunological indexes before and after treatment were observed for 24 weeks of antiviral therapy in the hepatitis B patients with ALT≥double upper limit of normal group. Results: In the ALT normal group, different virus load HBV had minor effects on Th17, Treg and Th17/Treg ratio. In the ALT≥2 times upper limit of normal group, with the virus load increased, Th17 (3.18%±0.79% in low replication group, 3.78%±0.92% in medium replication group and 4.57%±1.15% in high replication group), Treg cells (5.52%±1.58% in low replication group, 5.89%±1.84% in medium replication group and 6.37%±2.35% in high replication group) and their ratio Th17/Treg (0.57±0.25 in low replication group, 0.65±0.29 in medium replication group and 0.73±0.36 in high replication group) were significantly increased (P<0.05). After entecavir treatment 24 weeks, the patient’s HBV-DNA decreased significantly, Th17 (3.89%±1.02% vs. 2.06%±0.46%), Treg (6.02%±2.03% vs. 5.06%±1.25%), Th17/Treg ratio (0.65±0.28 vs. 0.41±0.14) decreased significantly (P<0.05). Conclusion: Investigation on the effects of HBV on Th17 and Treg cells and their ratios in different ALT states can clarify the effects of HBV on the body from the immunological perspective and can further understand the ALT grouping for antiviral treatment theoretical significance, which is helpful for clinical treatment.

Key words: Chronic hepatitis B, Viral load, Th17 cells, Treg cells

CLC Number:

R512.62

GAO Peng,LUO Yan-ping,LI Jun-feng,CHEN lin,MAO Xiao-rong. Effects of hepatitis B virus on Th17, Treg and Th17/Treg ratio in different alanine aminetransferase stages[J].Journal of Peking University (Health Sciences), 2022, 54(2): 272-277.

Figures/Tables 4

Table 1

Th17, Treg cells and their ratio in CHB patients with different viral load in normal ALT group (n = 111)"

Groups	n	Th17/%, $x -$ ±s	Treg/%, $x -$ ±s	Th17/ Treg, $x -$ ±s
Low replication group	37	1.83±0.36	4.98±1.21	0.38±0.12
Medium replication group	39	1.98±0.42	4.87±1.16	0.41±0.13
High replication group	35	1.88±0.38	4.95±1.21	0.39±0.13
F		0.462	0.524	0.679
P		0.635	0.604	0.407

Table 1

Table 2

Variance analysis of Th17, Treg cells and their ratio in CHB with ALT ≥ the upper limit of normal and < 2 times increase in different viral load groups (n = 108)"

Groups	n	Th17/%, $x -$ ±s	Treg/%, $x -$ ±s	Th17/ Treg, $x -$ ±s
Low replication group	37	2.61±0.57	5.21±1.35	0.51±0.19
Medium replication group	35	2.50±0.51	5.38±1.42	0.48±0.17
High replication group	36	2.76±0.61	5.34±1.21	0.52±0.20
F		0.437	0.659	0.526
P		0.648	0.427	0.603

Table 2

Table 3

Variance analysis of Th17, Treg cells and their ratio in different viral load groups in CHB patients with ALT≥2 times higher than the upper limit of normal (n = 117)"

Groups	n	Th17/%, $x -$ ±s	Treg/%, $x -$ ±s	Th17/ Treg, $x -$ ±s
Low replication group	40	3.18±0.79	5.52±1.58	0.57±0.25
Medium replication group	38	3.78±0.92	5.89±1.84	0.65±0.29
High replication group	39	4.57±1.15	6.37±2.35	0.73±0.36
F		7.995	6.005	7.268
P		<0.001	<0.001	<0.001

Table 3

Table 4

Changes of Th17, Treg cells and their ratios before and after entecavir treatment in CHB patients with ALT≥2 times higher than the upper limit of normal (n = 117)"

Groups	HBV-DNA(lg copies/mL), $x -$ ±s	Th17/%, $x -$ ±s	Treg/%, $x -$ ±s	Th17/ Treg, $x -$ ±s
Before treatment	6.37±1.86	3.89±1.02	6.02±2.03	0.65±0.28
After treatment	3.56±1.12	2.06±0.46	5.06±1.25	0.41±0.14
t	15.628	14.682	13.517	16.935
P	<0.001	<0.001	<0.001	<0.001

Table 4

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