e抗原阳性慢性乙型肝炎患者细胞免疫状态对聚乙二醇干扰素α2a疗效影响的初步报告

A preliminary report on the influence of baseline cellular immunity to the therapeutic responses of peg-interferon α2a in HBeAg positive chronic hepatitis B patients

慢性乙型肝炎(CHB)患者的干扰素(IFN)抗病毒疗效受病毒自身和宿主等因素的影响,而宿主的细胞免疫状态是IFN应答的重要因素之一。本文采用检测IFN治疗前基线时细胞免疫因子的方法,探讨治疗前细胞免疫状态对病毒学应答的影响。乙型肝炎e抗原(HBeAg)阳性CHB患者19例,其中男性14例,采用聚乙二醇IFN-α2a180μg皮下注射,每周1次,疗程48周,停药后观察24周。基线时检测CD3+、CD4+、CD8+、CD4+/CD8+、自然杀伤(NK)细胞、CD3+/CD25+、CD8+/CD28+、淋巴细胞转化试验(LTT)以及肿瘤坏死因子(TNF)、IFN-γ等细胞因子;同时观察血清转氨酶、病毒载量、e抗原等指标以判断疗效。所有病例治疗前、后进行肝组织学检查。按治疗终点(EOT)和随访终点(EOF)的应答或无应答分组比较基线时细胞免疫指标的差异。结果发现,在EOT时有15例应答,4例无应答,2组间基线时丙氨酸氨基转移酶(ALT)平均值分别为179.73±120.31和101.75±16.88,有显著差异(P=0.035);同时CD8+/CD28+有显著差异(P=0.019)。EOF时7例应答,12例无应答,基线时LTT在应答组和无应答组的结果分别为15895.43±5895.65和13792.08±2084.56,有极显著差异(P=0.003)。基线时的CD4+和CD3+/CD25+在HBeAg血清转换组与无转换组间有显著差异,分别为43.84∶32.08和2.91∶1.70,P值分别为0.038和0.035。EOF时肝组织学炎症程度分级应答组与无应答组相比有明显改善(P=0.0035)。结果提示,CHB患者IFN治疗前细胞免疫状态可能影响抗病毒疗效,但需扩大样本做进一步验证。

The antiviral efficacy of interferon in the treatment of patients with chronic hepatitis B （CHB） is influenced by the virus itself and the host factors. The host cellular immunity status is undoubtedly one of the most important factors of the interferon response. We analyzed baseline cellular immune factors before interferon treatment in order to understand the impact of immune status on virological response. Nineteen patients, including 14 males and 5 females with hepatitis B virus e antigen （HBeAg） positive CHB, received peg-interferon α 2a 180 μg per week for 48 weeks and follow-up for 24 weeks. All had liver biopsies at baseline and at the end of follow-up（EOF）. Hepatitis B virus （HBV） viral load, liver functions were detected before and every two months after antiviral therapy. Cellular immunity was evaluated by detecting CD3^＋, CD4 ^＋, CD8 ^＋, CD4^ ＋/CD8 ^＋, natural killer （NK） cell, CD3^ ＋/ CD25 ^＋, CD8 ^＋/CD28 ^＋ , lymphocyte transformation test （ LIT）, tumor necrosis factor （TNF） and IFN-γ, using flow cytometry. The virological response was defined as a HBV viral load below 1 × 10^5 copies/ml at end of treatment （EOT） and EOF. The results showed that 15 patients had an EOT virological response, while 7 patients had an EOF virological response. CD8 ^＋/CD28 ^＋ was significantly higher in patieats with an EOT virological response than that in non-responders （P = 0.019）, while LTT was significantly higher in patients with an EOF virological response （P = 0. 003）. CD4 ^＋ and CD3 ^＋/CD25 ^＋ were significantly higher in patients with HBeAg serum conversion （P = 0. 038 and 0.035 ）. Six patients had an EOF histological response（ P = 0.003 5 ）. Our data suggest that the cellular immune status of the host may be a good predictive indicator for the response of IFN therapy in CHB patients.