慢性乙型肝炎患者血清 HBV DNA 水平与 HBV 特异性、非特异性细胞毒性 T 淋巴细胞和自然杀伤细胞的关系。

Relationship between serum HBV DNA level and HBV-specific, nonspecific cytotoxic T lymphocytes and natural killer cells in patients with chronic hepatitis B.

机构信息

Department of Liver Diseases, Wuxi Hospital for Infectious Diseases, Wuxi, Jiangsu 214005, China.

出版信息

Chin Med J (Engl). 2009 Sep 20;122(18):2129-32.

PMID:19781297

Abstract

BACKGROUND

The response of patients with chronic hepatitis B (CHB) to antiviral therapy against hepatitis B virus (HBV) is related to the base line level of HBV DNA, but the mechanism is not clear. The present study aimed to understand the possible relationship between the level of HBV DNA and HBV-specific, nonspecific cytotoxic T lymphocytes (CTL) and natural killer (NK) cells of CHB patients and the mechanism how the HBV DNA level influences the antiviral therapeutic effect.

METHODS

Totally 100 adult patients with CHB who were positive for HBV DNA, HBeAg and (HLA)-A2 were enrolled into this study. HBV DNA was tested by real time fluorescence quantitative polymerase chain reaction (PCR). HBV specific and nonspecific CTL and NK cells were tested by flowcytometry. Serum alanine aminotransferase (ALT) and total bilirubin (TBil) were determined for each patient using routine biochemical tests. The 100 cases were assigned to two groups based on their HBV DNA level: group A had 48 cases, their HBV DNA level was 10(4) - 10(5) copies/ml, group B had 52 cases, their HBV DNA level was 10(6) - 10(7) copies/ml. HBV specific CTL, nonspecific CTL, NK cells, ALT and TBil of the two groups were compared.

RESULTS

HBV DNA level of groups A and B was (4.81 +/- 0.39) log(10) copies/ml and (6.81 +/- 0.40) log(10) copies/ml, respectively (t = 25.32, P < 0.001). HBV specific CTL and NK cells of group A were significantly higher than those of group B (P < 0.001 for both). Nonspecific CTL of group A was significantly lower than that of group B (P < 0.01). ALT and TBil of group A were significantly lower than those of group B (P < 0.01 and P < 0.05, respectively).

CONCLUSIONS

Serum HBV DNA level of patients with CHB is related to HBV specific CTL, nonspecific CTL and NK cells, which might result in inflammatory reaction of liver and cause more damage to liver function. Mechanism of HBV DNA level affecting the efficacy of anti-viral treatment may be related to the levels of HBV specific CTL and NK cells.

摘要

背景

慢性乙型肝炎（CHB）患者对乙型肝炎病毒（HBV）抗病毒治疗的反应与 HBV DNA 的基线水平有关，但机制尚不清楚。本研究旨在了解 CHB 患者 HBV DNA 水平与 HBV 特异性、非特异性细胞毒性 T 淋巴细胞（CTL）和自然杀伤（NK）细胞之间的可能关系，以及 HBV DNA 水平如何影响抗病毒治疗效果的机制。

方法

本研究共纳入 100 例 HBV DNA、HBeAg 和（HLA）-A2 阳性的成年 CHB 患者。采用实时荧光定量聚合酶链反应（PCR）检测 HBV DNA。采用流式细胞术检测 HBV 特异性和非特异性 CTL 和 NK 细胞。采用常规生化试验检测每位患者的血清丙氨酸氨基转移酶（ALT）和总胆红素（TBil）。根据 HBV DNA 水平将 100 例患者分为两组：A 组 48 例，HBV DNA 水平为 10（4）-10（5）拷贝/ml；B 组 52 例，HBV DNA 水平为 10（6）-10（7）拷贝/ml。比较两组患者的 HBV 特异性 CTL、非特异性 CTL、NK 细胞、ALT 和 TBil。

结果

A 组和 B 组的 HBV DNA 水平分别为（4.81±0.39）log（10）拷贝/ml 和（6.81±0.40）log（10）拷贝/ml（t=25.32，P<0.001）。A 组的 HBV 特异性 CTL 和 NK 细胞明显高于 B 组（均 P<0.001）。A 组的非特异性 CTL 明显低于 B 组（P<0.01）。A 组的 ALT 和 TBil 明显低于 B 组（均 P<0.01 和 P<0.05）。