免疫耐受期和非活动复制期乙型肝炎病毒感染者的肝脏病理与临床特征

目的了解免疫耐受期和非活动复制期HBV感染者的肝脏病理与临床特征,以及它们的区别。方法分析和比较54例免疫耐受期和47例非活动复制期HBV感染者年龄、性别、血清HBV DNA水平、肝脏炎症活动度及纤维化程度、肝脏HBsAg和HBcAg表达情况。并对不同血清ALT水平的肝脏炎症活动度及纤维化程度进行比较。结果两组患者性别构成比无明显差异,但非活动复制期HBV感染者年龄明显高于免疫耐受期[分别为（28．11±8．60）和（24．93±7．21）岁, P〈0．05]。免疫耐受期患者血清HBV DNA水平较高,106拷贝／ml以上者占94％,而89％的非活动复制期患者血清HBV DNA为阴性,其余患者表现为低水平复制。两组患者肝脏炎症活动度、HBsAg和HBcAg的表达无明显差异,但非活动复制期患者纤维化程度明显高于免疫耐受期（u=2．004, P〈0．05）。血清ALT在正常范围内较高水平患者的肝脏纤维化程度明显高于低水平患者（u=3.274, P〈0．01）。结论非活动复制期HBV感染者可能经历多次隐匿的免疫清除过程,因此年龄较大、纤维化程度较高。ALT持续处于正常范围内的较高水平患者可能纤维化程度较重,建议行肝脏病理学检查。     

血红素加氧酶-1表达对HBV复制的反向调控作用

目的评价血红素加氧酶-1（HO-1）对HBV复制的调控作用。方法采用分子克隆的方法分别构建人H（）_1真核表达载体——pH0和HO-1RNA干扰质粒——pHi，同HBV可复制性克隆pHBV1．3体外共转染人肝癌细胞系Huh-7，检测HBV抗原分泌情况和HBV相关mRNA含量。利用HBV急性感染小鼠模型，腹腔注射钴原卟啉（CoPP）IX和锌原卟啉（ZnPP）IX分别诱导和抑制HO-1表达，检测血清HO～1水平、HBV效价，免疫组织化学染色观察HBcAg在肝细胞内表达情况。分别在细胞水平和动物体内水平，评价HO-1表达对HBV复制的调控作用。结果同空载体共转染细胞相比，pHO共转染后HO-1的分泌水平明显上调（P〈0．01），HBsAg／HBeAg的分泌受到抑制（均P〈0．01）；pHi共转染后HO-1的分泌水平下降（P〈0．01），而HBsAg／HBeAg分泌增加（P均〈0．01）；但各组HBV相关RNA水平无明显差异。CoPPIX注射后诱导小鼠血清H0—1高表达（P％0．01），ZnPPIX则有效抑制了HO-1表达（P％0．01）。同对照组相比，CoPPIX组小鼠血清HBVDNA含量降低，肝脏内HBcAg阳性染色信号也随之明显减弱（P均〈0．01）；而ZnPPIX组小鼠血清HBVDNA含量增加，肝脏内HBcAg表达明显增强（均P〈0．01）。结论上调HO-1表达可有效抑制HBV复制，而下调其表达有利于HBV复制，且其可能是在转录后环节上发挥抗HBV作用。     

慢性乙肝患者肝组织内CD4+、CD8+和CD25+T淋巴细胞的表达和研究

探讨肝内免疫活性细胞与乙肝病毒（HBV）慢性感染的关系。运用免疫组织化学法分析54例CHB患者肝内CD25^＋T细胞以及部分患者肝内CD4^＋T细胞、CD8^＋T细胞的表达，并与9例正常肝组织进行比较。CD25^＋和CD8^＋T细胞在HBV感染组和非HBV感染组中的表达差异均存在显著性（P〈0．05和P〈0．01），CIM^＋T细胞在HBV感染组的表达虽有增多的趋势，但统计学上无显著意义（P〉0．05）。HBV感染组CD25^＋T细胞表达与I临床病理炎症分级和ALT的变化相关，随着炎症分级的加重和ALT的升高，其表达逐渐增强（P〈0．05和P〈0．01）。CD4^＋、CD8^＋T细胞表达与临床病理炎症分级和ALT的变化无关（P〉0．05）。CHB患者肝内CD25^＋T细胞表达增强与机体对HBV产生免疫耐受有关，CHB患者肝内CIM^＋、CD8^＋T淋巴细胞的表达异常，功能性免疫活性细胞浸润量不足，不能有效清除HBV。     

慢性乙型肝炎病毒感染者肝组织中程序性死亡分子-1及其配体的表达

目的 通过比较慢性HBV感染免疫耐受期和免疫清除期的患者肝组织中程序性死亡分子-1及其配体的表达情况,探讨其与机体免疫功能状态的关系.方法 收集肝组织活体检查标本并分为免疫清除期组25例、免疫耐受期组19例,用免疫组织化学方法检测标本汇管区中T淋巴细胞程序性死亡分子-1及其配体的表达情况,通过半定量评分系统计算其占CD3阳性细胞的百分数,用t检验比较两组病例间程序性死亡分子-1及其配体表达的差异.结果 免疫耐受期组肝组织汇管区T淋巴细胞中程序性死亡分子-1所占CD3阳性细胞比率为63.79%±6.94%,高于免疫清除期的54.36%±10.08%,两组比较,t=3.492,P<0.01,差异有统计学意义;程序性死亡分子配体-1于T淋巴细胞中的表达在免疫耐受期组(66.47%±8.40%)中高于免疫清除期组(52.64%±6.20%),两组比较,t=6.288,P<0.01,差异有统计学意义.程序性死亡分子配体-1在枯否细胞中的表达强度及范围在两组间差异无统计学意义(P>0.05).结论 慢性HBV感染者肝组织中的程序性死亡分子-1及其配体表达水平的差异反映了免疫耐受期和免疫清除期的不同免疫功能状态.

Abstract：

Objective To detect and compare the PD- 1/PD-L1 (programmed death 1/programmed death 1 ligand) expressions in the liver tissues of chronic HBV infection patients in immune tolerant phase and those in immune clearance phase. Methods Liver biopsy samples were divided into two groups: 25 samples from patients in immune clearance phase and 19 samples from patients in immune tolerant phase.PD-1/PD-L1 expressions on T lymphocytes in these liver biopsy specimens were detected by immunobis tochemistry method. Percentage of PD-1/PD-L1 positive cells among CD3 positive cells was calculated by semi-quantitative evaluation. Differences between the two groups were statistically analyzed. Results PD1/PD-L1 expressions were significantly higher in the patients in immune tolerant phase as compared to that in immune active phase (P < 0.05). No statistical difference found between the two groups for PD-L1 expression in Kupffer cells (P > 0.05). Conclusion PD-1/PD-L1 expression level can reflect the immune functions of chronic hepatitis B patients.     

连续性血液净化治疗老年多器官功能障碍及对机体免疫功能的影响

目的观察连续性血液净化（CBP）治疗老年多器官功能障碍综合征（MODS）及对机体免疫功能的影响。方法18例老年MODS患者，CBP治疗72h。在治疗0，24，48，72h时，测定单核细胞人类白细胞DR抗原（HLA—DR）的表达情况判断其抗原呈递功能（流式细胞仪），ELISA法测定细胞因予水平（TNF-α、IL-6、IL-10）；同时观察外周血单核细胞计数。结果18例患者在接受CBP治疗时，（1）单核细胞分泌功能：治疗前单核细胞分泌活跃，治疗后该组单核细胞分泌TNF-α、IL-6和IL-10均明显减少（P〈0．05）。（2）单核细胞抗原呈递功能：与正常人相比，MODS患者单核细胞表达HLA—DR都明显降低（P〈0．001）。治疗后明显改善（P〈0．01）。（3）单核细胞数量：治疗前，与正常指标比较单核细胞数量均明显降低，治疗后单核细胞数量明显上升接近正常水平。CBP治疗后，血浆TNF-α和IL-6水平较治疗前明显降低（P〈0．01）。（4）7例死亡患者IL-10较其他患者明屁升高，HLA—DR的表达则明显低下，CBP治疗后无明显改变。结论（1）CBP能明显改善老年MODS患者单核细胞功能，重建机体免疫系统内稳状态。（2）HLA-DR持续低表达和高血浆IL-10水平者预后差。（3）对免疫过度激化伴血浆细胞因子明硅升高者，CBP显示了是好的清除效果。     

e抗原阳性慢性乙型肝炎患者外周血树突状细胞干扰素β的表达

目的探讨慢性乙型肝炎患者树突状细胞干扰素β（IFN—β）表达与乙型肝炎病毒（HBV）感染后宿主免疫清除障碍的关系。方法选择e抗原阳性慢性乙型肝炎患者52例，健康对照48例，用免疫磁珠细胞分选乙型肝炎e抗原（HBeAg）法从外周血获得纯化的CD14^＋单核细胞，并用hOMCSF、hIL-4诱导单核细胞成为未成熟的髓样树突状细胞（mDC），加入polyI：C（25ug／ml）刺激后获得成熟的mDC，在刺激后0h、12h、24h、48h用流式细胞仪检测细胞表面分化抗原CD86、HLA-DR、CD1a，real—time PCR检测IFN8的表达变化。用ELISA方法检测mDC细胞上清液中IFN-β、IL-12、IL-10的浓度变化。结果两组mDC上0h IFN-β mRNA表达水平及细胞上清液中IFN—β浓度差异无统计学意义（P〉0．05）。健康对照组mDC在12hIFN—β mRNA表达水平及IFN-β浓度与0h相比显著升高（P〈0．05），较患者组0h、12h、24h、48h IFN—β表达显著升高（P〈0．05）。而患者组mDC刺激后12h、24h和48hIFN—β mRNA及IFN-β表达水平与0h相比无显著变化。与0h比较，健康对照组12h、24h、48hCD86表达水平较患者组显著上升（P〈0．05）。两组之间CD1a、HLA—DR表达差异无统计学意义。二组IL-10及IL-120h表达水平差异无统计学意义（P〉0．（15），患者组IL-10表达24h及48h与0h相比明显上升（P〈0．05）。而对照组12h、24h、48hIL-10表达水平没有明显上升。与之相反，患者组12h、24h、48hIL-12表达与0h相比表达水平没有明显上升，对照组在12hIL-12表达水平与0h相比差异有统计学意义（P〈0．05），24h、48hIL-12表达水平继续升高（P〈0．05）。结论慢性HBV感染者mDC受polyI：C刺激后IFN-β表达异常，协同刺激因子CD86表达低下，可能造成宿主对HBV感染的免疫清除障碍，导致疾病慢性化。     

TRAIL在HBV感染所致免疫损伤中的作用研究

目的观察肿瘤坏死因子相关凋亡诱导配体（TRAIL）在HBV感染所致免疫损伤中的作用。方法选择慢性乙肝患者（CHB）20例,乙肝病毒携带者（ASC）20例,正常健康者10例,ELISA检测其血清sTRAIL水平,同时检测血清IFN-γ和ALT水平。结果ASC组和CHB组sTRAIL水平明显高于正常健康组（P〈0．01）,且CHB组高于ASC组（P〈0．01）;CHB组IFN-γ水平明显高于正常组和ASC组（P〈0．05）,而正常组和ASC组之间差异无统计学意义（P〉0．05）。在CHB中sTRAIL水平与ALT的值呈正相关（P〈0．01）。结论TRAIL在IFN-γ的协同作用下,参与了HBV感染所致的免疫损伤,在HBV感染所致免疫损伤中起重要作用。     

HBV感染者血清趋化因子IP-10和RANTES的表达及其临床意义探讨

目的探讨HBV感染者血清IP—10和RANTES水平及其临床意义。方法采用ELISA定量检测正常人、自限性HBV感染者、慢性HBV携带者和慢性乙型肝炎患者血清IP-10和RANTES水平。结果与正常人比,自限性HBV感染者、慢性HBV携带者和慢性乙型肝炎患者血清IP-10（P=0．002,P=0．002,P=0．01）和RANTES（P=0．01,P=0．02,P〈0．001）表达均明显上调;自限性HBV感染者、慢性HBV携带者和慢性乙型肝炎患者之间血清IP-10水平无显著性差异（P〉0．05）,但自限性HBV感染者血清RANTES水平较其他两组明显升高（P±0．005,P=-0．03）;慢性乙型肝炎患者血清IP-10（P=0．001）和RANTES（P=0．02）水平均明显高于慢性HBV携带者;HBeAg阴性和阳性者之间两指标无显著性差异（P=0．08,P=0．42）;HBVDNA阳性者血清IP-10（P=-0．016）和RANTEs（P=0．02）水平均明显高于HBV DNA阴性者。结论IP-10和RANTES的趋化作用广泛参与了机体对HBV免疫应答的各个阶段,并在肝脏组织的炎性损伤中发挥了作用。     

乙型肝炎病毒B与C基因型感染者临床和有关免疫细胞计数的比较

目的探讨乙型肝炎病毒B与C基因型感染者临床和有关免疫细胞计数的差别。方法在128例乙型肝炎患者,采用微板核酸杂交-ELISA技术进行HBV基因分型,采用流式细胞仪检测T细胞亚群、非特异性CTL、辅助性T（Th1）、Th2细胞、自然杀伤（NK）细胞,在64例人白细胞抗原（HLA）A2阳性的CHB患者检测HBV特异性CTL。结果在128例CHB患者中,B基因型感染者70例（54．69％）,C基因型57例（44．53％）,B／C混合型1例（0．78％）;C基因型感染者血清丙氨酸氨基转移酶和总胆红素水平高于B基因型感染者（P〈0．01和P〈0．05）;C基因型感染者HBVDNA水平（P＜0．01）、HBeAg阳性率（P〈0．01）、Th1细胞（P〈0．05）和非特异性CTL（P〈0．01）高于B基因型感染者,而HBV特异性CTL低于B基因型（P〈0．01）。结论C基因型感染者肝功能损害比B基因型重,可能与HBV特异性CTL低,导致HBV DNA水平和HBeAg阳性率高有关。     

他汀类药物抑制桥本甲状腺炎甲减患者甲状腺细胞MHC-Ⅱ类基因的表达

采用流式细胞术检测人甲状腺上皮细胞（TEC）MHC-Ⅱ表达，发现桥本甲状腺炎（HT）甲减患者TEC MHC-Ⅱ表达明显高于正常对照[（40．7＋5．5）％vs（2．7＋2．1）％，P〈0．01]，γ干扰素可以显著促进TEC MHC—Ⅱ的表达（P〈0．01），他汀类药物（Simvastatin和Atrovastatin）可显著抑制γ干扰素诱导的TEC MHC—Ⅱ表达（均P〈0．05），从而降低相应的淋巴细胞活化，缓解HT的免疫紊乱。     

慢性乙型肝炎免疫清除期患者HBsAg基因多态性

目的 研究慢性乙型肝炎免疫清除期患者乙型肝炎病毒表面抗原(HBsAg)基因多态性.方法 设计特异性引物,自10例慢性乙型肝炎免疫清除期患者血清中扩增S基因片段,TA克隆法克隆到T载体中,随机选择克隆测序.结果 共20个克隆被测序,20个克隆S蛋白发现12个不同位点的32次变异.主要集中在T细胞表位,B细胞表位及a决定簇.结论 慢性乙型肝炎免疫清除期患者存在HBsAg变异,可能仍然存在HBsAg免疫耐受.     

慢性乙型肝炎病毒感染免疫耐受期患者的临床病理特征

目的:了解HBV慢性感染免疫耐受期患者的临床及病理学特征．方法:分析HBV感染不同时期380例患者的年龄、母婴垂直传播感染途径、乙肝家族史、肝细胞内HBsAg、HBcAg表达状况及肝组织病理学特征．结果:HBV慢性感染免疫耐受期患者年龄 16岁以下占61．8％,母婴垂直传播感染者占 55．0％,有乙肝家族史患者占46．6％,免疫耐受期患者89例肝组织内HBcAg阳性表达率 78．7％,均明显高于免疫活动期及感染非活动状态患者(x2=38．73,49．08,17．2,31．69, P<0．01)．免疫耐受期16岁以下的患者肝组织内HBsAg及HBcAg阳性表达率最高,分别占64．3％(45／75)和72．9％(51／79),显著高于免疫活动期和非活动HBV携带状态患者(x2= 17．51,31．17,P<0．001)．免疫耐受期16岁以上的患者肝组织内HBsAg及HBcAg阳性表达率最低,分别占35．7％(25／75)和27．1％(19／70),显著低于免疫活动期和非活动HBV携带状态患者(x2=17．51,x2=31．17,P<0．001)．结论:HBV慢性感染免疫耐受期患者中16岁以下者,母婴垂直传播感染者及乙肝家族史者所占比例明显高;HBV在肝组织复制表达以免疫耐受期患者最多,且16岁以下的患者占多数．     

Molecular characteristics and stages of chronic hepatitis B virus infection

Hepatitis B virus （HBV） is a common viral pathogen that causes a substantial health burden worldwide. Remarkable progress has been made in our under- standing of the natural stages of chronic HBV infection. A dynamic balance between viral replication and host immune response is pivotal to the pathogenesis of liver disease. Knowledge of the HBV genome organization and replication cycle can unravel HBV genotypes and molecular variants, which contribute to the heterogeneity in outcome of chronic HBV infection. Most HBV infections are spontaneously resolved in immunocompetent adults, whereas they become chronic in most neonates and infants at a great risk of developing complications such as cirrhosis and hepatocellular carcinoma （HCC）. Those with chronic HBV infection may present in one of the four phases of infection： immune tolerance, immune clearance [hepatitis B e antigen （HBeAg）-positive chronic hepatitis B （CHB）], inactive carrier state, and reactivation （HBeAg-negative CHB）. Understanding the dynamic nature of chronic HBV infection is crucial in the management of HBV carriers. Long-term monitoring and optimal timing of antiviral therapy for chronic HBV infection help to prevent progression of HBV-related liver disease to its later stage, particularly in patients with higher risk markers of HCC, such as serum DNA concentration, HBeAg status, serum aminotransferase, HBV genotypes, and pre-core or core mutants.     

Immune therapy including dendritic cell based therapy in chronic hepatitis B virus infection

Hepatitis B virus (HBV) infection is a global public health problem. Of the approximately 2 billion people who have been infected worldwide, more than 400 million are chronic carriers of HBV. Considerable numbers of chronic HBV carriers suffer from progressive liver diseases. In addition, all HBV carriers are permanent source of this virus. There is no curative therapy for chronic HBV carriers. Antiviral drugs are recommended for about 10% patients, however, these drugs are costly, have limited efficacy, and possess considerable side effects. Recent studies have shown that immune responses of the host to the HBV are critically involved at every stage of chronic HBV infection: (1) These influence acquisition of chronic HBV carrier state, (2) They are important in the context of liver damages, (3) Recovery from chronic HBV-related liver diseases is dependent on nature and extent of HBV-specific immune responses. However, induction of adequate levels of HBV-specific immune responses in chronic HBV carriers is difficult. During the last one decade, hepatitis B vaccine has been administered to chronic HBV carriers as a therapeutic approach (vaccine therapy). The present regimen of vaccine therapy is safe and cheap, but not so effective. A dendritic cell-based therapeutic vaccine has recently been developed for treating chronic HBV infection. In this review, we will discuss about the concept, scientific logics, strategies and techniques of development of HBVspecific immune therapies including vaccine therapy and dendritic cell-based vaccine therapy for treating chronic HBV infection.     

Peripheral T-lymphocyte subpopulations in different clinical stages of chronic HBV infection correlate with HBV load

AIM： To characterize the peripheral T-cell subpopulation profiles and their correlation with hepatitis B virus （HBV） replication in different dinical stages of chronic HBV infection.
METHODS： A total of 422 patients with chronic HBV infection were enrolled in this study. The patients were divided into three stages： immune-tolerant stage, immune active stage, and immune-inactive carrier stage. Composition of peripheral T-cell subpopulations was determined by flow cytometry. HBV markers were detected by enzyme-linked immunosorbent assay. Serum HBV DNA load was assessed by quantitative real-time poiymerase chain reaction.
RESULTS： CD8^＋ T-cells were significantly higher in patients at the immune-tolerant stage than in patients at the immune-active and -inactive carrier stages （36.87 ± 7.58 vs 34.37 ± 9.07, 36.87 ± 7.58 vs 28.09 ± 5.64, P 〈 0.001）. The peripheral blood in patients at the immune-tolerant and immune active stages contained more CD8^＋ T-cells than CD4^＋ T-cells （36.87 ± 7.58 vs 30.23 ± 6.35, 34.37 ± 9.07 vs 30.92 ± 7.40, P 〈 0.01）, whereas the peripheral blood in patients at the immune- inactive carrier stage and in normal controls contained less CD8^＋ T-cells than CD4^＋ T-cells （28.09 ± 5.64 vs 36.85 ±6.06, 24.02 ± 4.35 vs 38.94 ± 3.39, P 〈 0.01）. ANOVA linear trend test showed that CD8^＋ T-cells were significantly increased in patients with a high viral load （39.41 ± 7.36, 33.83 ± 7.50, 31.81 ± 5.95 and 26.89 ± 5.71, P 〈 0.001）, while CD4^＋ T-cells were significantly increased in patients with a low HBV DNA load （37.45 ± 6.24, 33.33 ± 5.61, 31.58 ± 6.99 and 27.56 ± 5.49, P 〈 0.001）. Nultiple regression analysis displayed that log copies of HBV DNA still maintained its highly significant coefficients for T-cell subpopulations, and was the strongest predictors for variations in CD3^＋, CD4^＋ and CD8^＋ cells and CD4^＋/CD8^＋ ratio after adjustment for age at HBV-infection, maternal HBV-infection status, presence of hepatitis B e antigen and HBV mutation.
CONCLUSION： Differences in peripheral T-cell subpopulation profiles can be found in different clinical stages of chronic HBV infection. T-cell impairment is significantly associated with HBV load.     

Serum soluble interleukin-2 receptor levels in patients with chronic hepatitis B virus infection and its relation with anti-HBc

AIM:To investigate the relationship between serumsoluble interleukin-2 receptor(sIL-2R)level and anti-HBcin patients with chronic hepatitis B virus(HBV)infection.METHODS:Sera from 100 patients with chronic HBVinfection and 30 healthy controls were included in thisstudy.The patients were divided into group A[HBsAg( ),HBeAg( )and anti-HBc( ),n=50]and group B[HBsAg( ),HBeAg( )and anti-HBc(-),n=50].sIL-2R levelswere determined using ELISA.HBV DNA and alanineaminotransferase(ALT)were also detected.RESULTS:Serum sIL-2R levels were significantly higherin patients with chronic HBV infection than in healthycontrols.Moreover,serum sIL-2R levels were significantlyhigher in patients with HBsAg( ),HBeAg( )and anti-HBc( )(976.56±213.51×10~3 U/L)than in patients withHBsAg( ),HBeAg( )and anti-HBc(-)(393.41±189.54×10~3 U/L,P<0.01).A significant relationship was foundbetween serum sIL-2R and ALT levels(P<0.01)inpatients with chronic HBV infection,but there was nocorrelation between sIL-2R and HBV DNA levels.Theanti-HBc status was significantly related to the age ofpatients(P<0.01).CONCLUSION:The high sIL-2R level is related topositive anti-HBc in chronic hepatitis B patients.Positiveanti-HBc may be related to T-lymphocyte activation andnegative anti-HBc may imply immune tolerance in thesepatients.     

乙型肝炎病毒母婴传播阻断的共识与争议

慢性乙型肝炎因其严重的不良临床结局如肝硬化或肝细胞癌而成为严重的公共卫生问题,而母婴传播是导致慢性HBV感染的最主要原因。尽管HBV阳性孕妇所生的新生儿在出生后24h之内应用了乙型肝炎疫苗和乙型肝炎免疫球蛋白（HBIG）进行联合免疫阻断,仍然有大约10％左右的新生儿感染了HBV,特别是高病毒载量的孕妇。本文将就HBV母婴传播的特点、目前在阻断措施方面达成的共识和存在的争议进行论述。     

B7-H1 expression is upregulated in peripheral blood CD14+ monocytes of patients with chronic hepatitis B virus infection, which correlates with higher serum IL-10 levels

Chronicity in hepatitis B virus (HBV) infection is maintained by increased type 2 T-helper cell response, possibly because of increased interleukin-10 (IL-10) productions. B7-H1 can negatively regulate T-cell responses via its receptor, programmed death 1. Ligation of B7-H1 to T-cells can result in the preferential secretion of IL-10. In this study, we investigated whether there was an upregulated expression of B7-H1 in peripheral blood mononuclear cells in patients chronically infected by HBV and further explored the correlation between B7-H1 expression and serum interleukin 2, interferon-gamma, IL-10, HBeAg, alanine aminotransferase (ALT) levels and viral load. Fifty-five patients with chronic HBV infection and 20 healthy controls (HCs) were enrolled in the present study. The results showed that in patients with chronic hepatitis B CD14+ monocytes but not CD3+ and CD19+ cells had a significantly increased expression of B7-H1 compared with HCs, which positively correlates with serum IL-10 levels and the presence of HBeAg and negatively correlates with serum ALT levels. In conclusion, chronic HBV patients harbour an increased B7-H1 expression in CD14+ monocytes compared with controls, which may be responsible for the increased serum IL-10 levels. This might be an important way by which HBV evades an adequate immune response, leading to viral persistence and disease chronicity.     

Expression Profiles of Circulating Cytokines,Chemokines and Immune Cells in Patients With Hepatitis B Virus Infection

Background:

Immune cells and molecules play a vital role in initiating, maintaining, regulating immunological homeostasis and inflammation in many pathological and physiological processes; however, the changes on expressions and functions of these cells and molecules in hepatitis B virus (HBV) infection have not been elucidated well.

Objectives:

The current study aimed to determine the expression pattern of different cytokines, chemokines, immune cells in HBV infection and their association with disease progression.

Patients and Methods:

Sixty-nine patients with chronic HBV infection were enrolled. Five immune cell subsets and 46 cytokines and chemokines were analyzed by flow cytometry and Luminex 200.

Results:

In comparison to healthy individuals and asymptomatic HBV carriers, expression of CXCL9, CXCL10, CXCL11, and IL-10 were elevated in patients with chronic active HBV and had positive correlation with ALT levels. In contrast, G-CSF, MCP-3, and IFN-γ levels were significantly decreased in patients with chronic active HBV infection in contrast to carriers and healthy individuals; however, these down regulations did not show any correlation with either virological findings or liver inflammation. Although the proportion of CD4⁺ CD25 ^high regulatory T cells (Tregs) was higher in patients with HBV infection than in healthy controls, no correlations were found between Tregs and other cytokines or chemokines.

Conclusions:

CXCR3-associated chemokines might contribute to liver inflammation in chronic hepatitis B, while MCP-3 and G-CSF were inhibited by HBV infection. Host immune response was suppressed as manifested by an increase in CD4⁺ CD25^high Tregs and IL-10 as well as a decrease in IFN-γ. Exploiting the expression pattern of cytokine and chemokine may help to develop a better understanding of chronic HBV infection pathogenesis.