抗病毒治疗对慢性乙型肝炎患者免疫球蛋白及补体的影响

The impact of serum levels of immunoglobulin and complement during nucleoside antiviral treatment inchronic hepatitis B patients

目的探讨慢性乙型肝炎（慢乙肝）患者使用核苷类抗病毒药物前后对免疫球蛋白及补体的影响。方法选取慢乙肝患者共157例，50例接受抗病毒治疗，分别在其使用核苷类抗病毒药物前，抗病毒治疗后的第1、2、3、4周，用ELISA法检测HBV血清学标志物，RT-PCR法检测HBVDNA，免疫比浊法测定IgG、IgA、IgM和C3、C4、总补体（CH50）、C反应蛋白（CRP）。均数比较采用t检验和Mann-Whitney检验。相关分析采用Pearson相关系数检验。结果慢性乙型重型肝炎及肝硬化组患者的IgA、IgM明显高于慢乙肝组（P％0．01）。三组间c3、C4、CH50、CRP水平比较，差异有统计学意义。HBeAg阳性与HBeAg阴性患者的C3、IgM、IgG及HBVDNA水平比较，差异有统计学意义。HBeAg阳性者中，高HBVDNA水平的患者与低水平HBVDNA患者相比，其IgA、IgM、C3和CH50水平均差异有统计学意义。HBeAg阴性患者中，高HBVDNA水平的患者与低水平HBVDNA患者相比，IgA水平差异有统计学意义。经抗病毒治疗，三组患者的免疫球蛋白及HBVDNA较治疗前下降，补体系统较前回升，在第4周时差异有统计学意义。HBVDNA的水平与C3呈负相关（r=-0．78，P=0．021）。HBeAg定量与C3呈正相关（r=0．87，P=0．015）。结论血清免疫球蛋白、CRP、C3、C4和CH50可以反映肝脏炎性活动状态；C3的变化可以预测抗病毒治疗的效果。

Objective To evaluate the effects of nucleoside/nucleotide analogue treatment on immunoglohulin and complement in patients with chronic hepatitis B （CHB）. Methods A total of 157 CHB patients were recruited and divided into CHB group, liver cirrhosis （LC） group and severe hepatitis B （SHB） group. There were 50 patients who received oral antiviral treatment （lamivudine 100 mg/d, or entecavir 0. 5 mg/d, or telbivudine （C3, C4）, C-reaction protein （CRP）, hemolytic 600 mg/d）. Serum levels of complement 3 and 4 complement （CH50）, immunoglobulin G, M, A（IgG, IgM, IgA）, hepatitis B surface antigen （HBsAg） and hepatitis B e antigen （HBeAg） were detected by enzyme-linked immunosorbent assay （ELISA） or immunoturbidimetry. Hepatitis B virus （HBV） DNA was quantified by real-time polymerase chain reaction （RT-PCR） before and 1, 2, 3 and 4 weeks after nucleoside antiviral therapy. Comparison of means was done by t test and Mann-Whitney test. The correlation was analyzed by Pearson correlation coefficient test. Results Serum IgA and IgM levels of SHB and LC patients were significantly higher than those of CHB patients （P〈0.01）. Levels of C3, C4, CH50 and CRP were significantly different among three groups. Levels of C3,IgM,IgG and HBV DNA in HBeAg positive patients were significantly different from those in HBeAg negative patients. There was a statistically significant difference of IgA, IgM, C3 and CH50 levels between patients with high HBV DNA level and low HBV DNA level in HBeAg-positive patients. While in the HBeAg-negative patients, only the IgA level was significantly different with HBV DNA levels. After anti-viral treatment, immunoglobulin and HBV DNA levels were all decreased in three groups, while the serum complement level was increased compared to baseline, and the differences became significant at week 4 of treatment. HBV DNA level was negatively correlated with C3 （r= --0.78, P=0. 021） and HBeAg titer was positively correlated with C3 （r=0. 87, P=0. 015）. Conclusions The immunoglobulin, CRP, C3, C4, and CHS0 could reflect the inflammatory activity in liver. The changes of C3 level can predict the efficacy of antiviral therapy.