目的 探討乙肝疫苗誘導(dǎo)樹突狀細(xì)胞（DC）和特異性細(xì)胞毒性T淋巴細(xì)胞（CTL）表達(dá)促進(jìn)聚乙二醇干擾素α（peg-IFN-α）治療慢性乙型病毒性肝炎（CHB）患者病毒學(xué)應(yīng)答的效果及安全性。方法 2016年1月－2019年1月南京軍區(qū)福州總醫(yī)院肝膽內(nèi)科和福建醫(yī)科大學(xué)孟超肝膽醫(yī)院收治的120例HBeAg陽性CHB初治患者，隨機(jī)分為疫苗誘導(dǎo)＋pegIFN-α治療組（治療組）和peg-IFN-α單藥治療組（對照組），各60例。治療組采取HBV疫苗皮下多點注射，20 μg/次，1次/4周，共3次；誘導(dǎo)開始2周后注射peg-IFN-α180μg/次，1次/7 d，總療程50周。對照組皮下注射peg-IFN-α 180 μg/次，1次/7 d，總療程48周。檢測兩組患者治療治療前后12周的免疫學(xué)指標(biāo)（DCs計數(shù)、IL-12水平和HBV特異性CTL細(xì)胞IFN-γ反應(yīng)率和反應(yīng)強度）；24和48周時HBV DNA陰轉(zhuǎn)率、HBeAg血清學(xué)轉(zhuǎn)換率及HBsAg轉(zhuǎn)陰率。結(jié)果 最終108例完成實驗（治療組55例，對照組53例），兩組患者抗病毒治療前DCs數(shù)量和IL-12分泌水平均處于較低的水平，抗病毒治療12周后DCs數(shù)量和IL-12水平較療前均有明顯上升，差異有統(tǒng)計意義（P<0.001）。治療組與對照組相比DCs計數(shù)、IL-12水平和特異性CTL細(xì)胞IFN-γ反應(yīng)強度，差異具有統(tǒng)計學(xué)意義（P<0.001）。治療24周、48周的HBV DNA轉(zhuǎn)陰率、HBeAg血清轉(zhuǎn)換率，兩組比較差異無統(tǒng)計學(xué)意義；但治療組48周HBsAg轉(zhuǎn)陰率，治療組明顯高于對照組兩組比較差異有統(tǒng)計學(xué)意義（P<0.05）。結(jié)論 多點注射乙肝疫苗能夠誘導(dǎo)CHB患者樹突狀細(xì)胞和HBV特異性CTL細(xì)胞表達(dá)及其細(xì)胞因子的分泌，提高聚乙二醇干擾素α治療CHB患者的HBsAg轉(zhuǎn)陰率。

Objective To investigate the effect of hepatitis B vaccination on dendritic cells(DC) and cytotoxic T lymphocyte (CTL) expressions and virological response in patients with chronic hepatitis B being treated with pegylated interferon. Methods A total of 120 patients with HBeAg positive treatment-naive chronic hepatitis B (CHB) who visited the outpatient service or were hospitalized in Fuzhou General Hospital and Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2016 to January 2019 were divided randomly intotreatment group (60 cases) and control group (60 cases). The patients in the two groups were treated with pegylated interferon alpha(180 μg, subcutaneous injection, once a week) for 48 weeks, on this basis, the patients in the induction group were treated with hepatitis B vaccination (20 μg, multiple subcutaneous injection, once four weeks) for 3 times before interferon treatment for 2 weeks. The levels of dendritic cells andIL-12, and the magnitudes of IFN-γ releasing induced by HBVspecific cytotoxic T lymphocyte were measured before and 12 weeks after treatment. The negative rate of HBV-DNA, HBsAg, serological conversion rate of HBeAg of the patients in the two groups were observed after 24 and 48 weeks. Results Finally 108 cases (55 in the treatmentgroup and 53 in the control group) completed the course of treatment, and involved in the analysis of results. After 12 weeks of treatment, the IL-12 levels of serum and DCs amounts in both groups were significantly higher than those before treatment (P < 0.001). The DCs amounts, IL-12 levels of serum and the magnitudes of IFN-γ releasing induced by HBVspecific CTL were significantly different between two group (P < 0.001). There were no significant differences of HBV-DNA negative rates and HBeAg seroconversion rates between the two groups after 24 and 48 weeks treatment. The negative rate of HBsAg was significantly higher in the treatment group than that in the control group after 48 weeks treatment (P < 0.05). Conclusion It is found that hepatitis B vaccination could induce DC and CTL proliferation, promote cytokines secreting, and improve HBV-DNA negative rate in patients with chronic hepatitis B being treated with pegylated interferon.

R282.710.5

福建省社會發(fā)展引導(dǎo)性（重點）項目（2016Y0068）