慢性乙型肝炎患者外周血NK细胞和T淋巴细胞计数变化及其临床意义

目的观察慢性乙型肝炎患者外周血NK细胞和T淋巴细胞数量的变化。方法在56例乙型肝炎肝衰竭、49例HBeAg阳性慢性乙型肝炎和41例乙型肝炎病毒携带者使用流式细胞仪检测外周血CD3+T细胞、CD3+CD4+T细胞、CD3+CD8+T细胞和NK(CD3-CD16+CD56+)细胞占淋巴细胞的比率(%)。结果肝衰竭患者CD3+T细胞和CD3-CD16+CD56+NK细胞计数比慢性乙型肝炎患者和乙型肝炎病毒携带者显著性降低(P0.05);慢性乙型肝炎患者CD3-CD16+CD56+NK细胞计数比乙型肝炎病毒携带者显著性升高(P0.05)。结论乙型肝炎肝衰竭患者外周血T细胞和NK细胞数量减少,而HBeAg阳性慢性乙型肝炎患者外周血T细胞数量增多。     

乙型肝炎患者外周血CD4^＋T细胞Notch1蛋白的表达

目的探讨CD4^＋T细胞Notch1蛋白在乙型肝炎病人发病机制中的作用。方法采用流式细胞仪检测23例慢性乙型肝炎患者、8例急性乙型肝炎患者和10例健康对照者的外周血CD4^＋T细胞Notch1蛋白表达水平,并应用荧光定量PCR方法测定上述研究对象血中HBV-DNA滴度。结果慢性乙型肝炎组外周血CD4^＋T细胞Notch1蛋白的平均百分率为（3.17±0.65）%,与急性乙型肝炎组（1.85±0.46）%和健康对照组（2.18±0.57）%比较都有极其显著差异（P〈0.001）;急性乙型肝炎组外周血CD4^＋T细胞Notch1蛋白的百分率与健康对照组比较差异无统计学意义（P〉0.05）;慢性乙型肝炎患者外周血CD4^＋T细胞Notch1蛋白的百分率与HBV-DNA滴度呈正相关。结论Notch1蛋白在慢性乙型肝炎患者外周血中表达增高,说明其可能参与乙型肝炎病情的发展及病毒的清除。     

CD4+CD25+调节性T细胞在慢性乙型肝炎及相关疾病发生发展中的作用

慢性乙型肝炎是临床上常见的感染性疾病,可进展为肝硬化、肝癌.患者体内乙型肝炎病毒的持续复制和机体免疫功能的低下与疾病的发生发展密切相关.调节性T细胞具有免疫无能、免疫抑制的特性,近年来发现其可能与慢性乙型肝炎的发病机制有关.此文对CD4+CD25+调节性T细胞在慢性乙型肝炎发生发展中的作用作一综述.     

CD4＋CD25＋调节性T细胞在慢性乙型肝炎及相关疾病发生发展中的作用

慢性乙型肝炎是临床上常见的感染性疾病，可进展为肝硬化、肝癌。患者体内乙型肝炎病毒的持续复制和机体免疫功能的低下与疾病的发生发展密切相关。调节性T细胞具有免疫无能、免疫抑制的特性，近年来发现其可能与慢性乙型肝炎的发病机制有关。此文对CD4＋CD25＋调节性T细胞在慢性乙型肝炎发生发展中的作用作一综述。     

乙型肝炎患者树突状细胞内HBV DNA存在状况的研究

目的:研究慢性乙型肝炎患者外周血培养的树突状细胞(DC)内乙型肝炎病毒DNA(HBV DNA)存在状况,分析HBV DNA与DC功能下降的内在联系.方法:从慢性乙型肝炎患者外周血中分离单个核细胞,在含rhGM-CSF,rhIL-4的培养基中诱导培养为DC,用流式细胞仪检测乙肝患者DC的表型变化,用流式细胞仪分选出树突状细胞,应用PCR技术检测DC内HBV DNA存在状况.结果:①表达于慢性乙型肝炎患者DC表面的共刺激分子(B7-1,B7-2,CD1α)及MHC-Ⅱ类分子(HLA-DR)的水平明显降低.②树突状细胞内HBV DNA检测结果阳性.结论:乙型肝炎患者树突状细胞内存在HBV DNA感染,慢性乙型肝炎患者树突状细胞与正常人相比,表型表达降低.     

免疫清除期慢性乙型肝炎患者外周血T细胞程序性坏死因子-1表达及其意义

目的 明确程度性坏死因子（PD-1）在免疫清除期慢性乙型肝炎患者外周血T细胞表达状态及其对患者病毒载量水平和生化指标的影响.方法 45例ALT升高的慢性乙型肝炎患者被纳入本研究.应用流式细胞术对所有患者的外周血总CD8+T细胞和CD4+T细胞PD-1表达百分比和表达强度进行检测,其中18例患者接受肝组织活检,并应用免疫...     

干扰素-α对慢性乙型肝炎患者CD1α树突状细胞的体内诱导作用

目的探讨IFN-α对慢性乙型肝炎患者CD1α树突状细胞的体内诱导作用。方法在干扰素-α(IFN-α)抗乙型肝炎病毒的同时,采用流式细胞检测技术,检测21例慢性乙型肝炎患者外周血CD1α树突状细胞状况,观察IFN-α仅治疗前后慢性乙型肝炎患者CD1α树突状细胞的变化,同时观察对照组(15例)慢性乙型肝炎患者CD1α树突状细胞的变化。结果IFN-α治疗组在IFN-α治疗3个月后CD1α树突状细胞占外周血单个核细胞的比率增加,对照组慢性乙型肝炎患者CD1α树突状细胞差异无显著性。抗病毒治疗组中,治疗后HBV-DNA转阴组CD1α树突状细胞占外周血单个核细胞的比率高于未转阴组。结论IFN-α在体内有诱导外周血单个核细胞产生树突状细胞的作用,IFN-α对慢性乙型肝炎患者CD1α树突状细胞的体内诱导作用可能是IFN-α抗乙型肝炎病毒的一重要免疫机制。     

CD4+ CD25+调节性T细胞在重型乙型肝炎发病中的作用

目的探讨CD4 CD25 调节性T细胞在重型乙型肝炎病人发病机制中的作用。方法采用流式细胞仪检测30例重型乙型肝炎患者、20例慢性乙型肝炎患者、20例无症状乙肝病毒携带者和10例健康的外周血CD4 CD25 调节性T细胞(CD4 CD25 Treg)的水平,并应用荧光定量PCR方法测定上述研究对象血中HBVDNA滴度。结果(1)重型乙型肝炎组外周血CD4 CD25 调节性T细胞的平均百分率为(2.63±0.83)%,较慢性乙型肝炎组的(4.15±1.17)%有显著差异(P<0.05),较无症状乙肝病毒携带者组及健康对照组则有极其显著差异(P均<0.01);(2)慢性乙型肝炎组外周血CD4 CD25 调节性T细胞的百分率与无症状乙肝病毒携带者及健康对照组,有显著的差异(P<0.05);无症状乙型肝炎携带者组外周血调节CD4 CD25 T细胞的百分率为(8.32±2.72)%,与健康对照组(8.10±2.65)%比较无差异;(3)重型乙型肝炎组外周血HBVDNA滴度为1.2×104拷贝/ml,与慢性乙型肝炎组(2.3×106拷贝/ml)和无症状乙肝病毒携带者(7.8×105拷贝/ml)相比较,有极其显著差异(P均<0.01);慢性乙型肝炎组外周血HBVDNA滴度与无症状乙肝病毒携带者相比,无差异;(4)无症状乙型肝炎携带者;慢性乙型肝炎和重型乙型肝炎,患者外周血CD4 CD25 调节性T细胞的百分率与HBVDNA滴度呈正相关。结论(1)CD4 CD25 调节性T细胞能抑制T细胞对乙型肝炎病毒的免疫反应,从而抑制乙型肝炎病毒诱导的对肝细胞的免疫攻击的发生;(2)不同乙型肝炎病人外周血CD4 CD25 调节性T细胞的百分率与HBVDNA滴度呈正相关,表明CD4 CD25 调节性T细胞数量对体内HBV载量具有较大的影响;(3)CD4 CD25 调节性T细胞在重型乙型肝炎的病情进展及病毒抑制清除等方面起着重要的作用。     

慢性乙型肝炎患者树突状细胞的分离培养

在我国慢性乙型肝炎是引起肝硬变和肝细胞癌最常见的病因。慢性乙型肝炎形成的机制可能是机体免疫功能低下,不能产生有效的针对HBV特异性的CTL反应,不能彻底清除HBV,使HBV病毒得以不断增殖,导致病变进行性发展。因此,治疗慢性乙型肝炎最根本的途径就是清除病毒。有研究表明,细胞免疫应答,包括辅助T细胞(Th)和细胞毒T细胞(CTL)应答,在机体清除乙型肝炎病毒(HBV)的过程中发挥重要作用,树突状细胞(dendritic cells,BC)是一种最具潜能的抗原提呈细胞,并且在增强或调节细胞介导的免疫反应中起     

乙型肝炎慢性化机理研究现状与问题

乙型肝炎慢性化机理研究现状与问题黄爱龙，张定凤乙型病毒性肝炎为波及全球的传染病，易于慢性化、重症化。早在乙型肝炎免疫学初期，意大利学者Ｆｅｒｒａｒｉ［１］曾比较急性自限性乙型肝炎、慢性乙型肝炎和无症状表面抗原（ＨＢｓＡｇ）携带者外周血单个核细胞对不同...     

慢性HBV感染的免疫治疗

目前现有的抗病毒药物对慢性HBV感染的疗效不甚满意.HBV感染的控制和清除有赖于机体的免疫系统,其感染慢性化与机体特异性免疫,尤其是细胞免疫功能低下密切相关.旨在通过增强或恢复机体抗HBV免疫功能以控制和清除HBV感染的免疫治疗是被人们寄予厚望的一种治疗策略,备受关注.本文将从树突状细胞、调节性T细胞、CD8~ T细胞、治疗性疫苗等几个方面对近几年慢性HBV感染的免疫学和免疫治疗研究进展进行综述.     

乙型肝炎患者外周血单个核细胞对HBV不同区抗原的增殖反应

目的进一步明确外周血细胞免疫在ＨＢＶ感染过程中的作用。方法对２０例急性乙型肝炎（乙肝）患者、２３例慢性乙肝患者、２０例正常献血员进行了研究,用氮蓝四唑实验（ＭＴＴ）测定乙肝患者外周血单个核细胞（ＰＢＭＣ）对ＨＢＶ不同区抗原的增殖反应。结果在急性乙肝患者ＰＢＭＣ对抗原的增殖反应大于慢性乙肝患者及正常对照,ＰＢＭＣ对ＨＢｃＡｇ的增殖反应最高,ＨＢｅＡｇ次之,而对ＨＢｓＡｇ的反应均较弱。另外,无论在急性、慢性患者,其ＰＢＭＣ对抗原的增殖反应水平与血清丙氨酸转氨酶（ＡＬＴ）的变化无明显相关性。血清ＨＢＶＤＮＡ阴性、ＨＢｅＡｇ阴性的慢性肝炎或慢性肝炎急性发作患者,其ＰＢＭＣ对ＨＢＶ抗原的增殖反应较弱,在血清ＨＢＶＤＮＡ或ＨＢｅＡｇ阳性患者,增殖反应较强,而当血清ＨＢＶＤＮＡ、ＨＢｅＡｇ均阳性时,增殖反应最强,表明外周细胞免疫与ＨＢＶ的复制及清除相关。结论ＨＢＶ感染后,外周血中存在对ＨＢＶ抗原的细胞免疫,这种细胞免疫可能与乙肝的发病及ＨＢＶ的清除有关。     

Proliferating cell nuclear antigen assessed by a computer-assisted image analysis system in patients with chronic viral hepatitis and cirrhosis

BACKGROUND: Assessment of liver cell proliferation by immunodetection of proliferating cell nuclear antigen may predict regenerative potential and survival of liver and hepatocellular carcinoma risk in patients with chronic viral hepatitis. AIM: To evaluate proliferating cell nuclear antigen status and its clinical significance in a large cohort of patients with chronic viral hepatitis and different degree of liver damage by a computer assisted imaging analysis system. MATERIALS: Liver biopsies from 358 patients with chronic hepatitis (259 males, 49 years, 63% with hepatitis C infection, 27% with hepatitis B virus, 10% with multiple infections) were studied. METHODS: Proliferating cell nuclear antigen was localised by immunoperoxidase on microwave oven pre-treated formalin-fixed, paraffin embedded sections using PC10 monoclonal antibody. Proliferating cell nuclear antigen labelling index was calculated by an automated imaging system (Immagini e Computers, Milan, Italy). RESULTS: Mean proliferating cell nuclear antigen labelling index ranged from 0.1% for patients with minimal changes to 3.6% for those with cirrhosis and hepatocellular carcinoma. Overall, proliferating cell nuclear antigen labelling index was higher in males, in older patients, in multiple infections and in hepatitis C virus compared to hepatitis B virus related cases. By linear regression analysis, proliferating cell nuclear antigen labelling index correlated with older age, male gender; higher transaminase levels, hepatitis C virus, higher histological gradIng and staging: by multivariate analysis male gender, hepatitis C virus, higher grading and staging resulted as independent variables. Both hepatitis C virus or hepatitis B virus cirrhotics had similar liver cell proliferation rate but those with hepatitis B virus had higher prevalence of liver cell dysplasia with respect to those with hepatitis C virus. CONCLUSIONS: Proliferating cell nuclear antigen labelling index was a reliable assay for assessing liver cell proliferation rate in patients with chronic viral hepatitis and correlated with liver disease severity     

Hepatitis B and end-stage liver disease

Hepatitis B virus (HBV) is the most common cause of chronic hepatitis and end-stage liver disease worldwide. Untreated, chronic hepatitis B acquired early in life results in cirrhosis, liver failure, or hepatocellular carcinoma in up to 40% of individuals. Until recently, the options for a patient who had end-stage hepatitis B cirrhosis were severely limited, but during the past 15 years great strides have been made in prevention and treatment of hepatitis B cirrhosis. This article reviews recent advances in the understanding of the natural history, prevention, and medical management of HBV-related end-stage liver disease.     

The influence of the human genome on chronic viral hepatitis outcome

The mechanisms that determine viral clearance or viral persistence in chronic viral hepatitis have yet to be identified. Recent advances in molecular genetics have permitted the detection of variations in immune response, often associated with polymorphism in the human genome. Differences in host susceptibility to infectious disease and disease severity cannot be attributed solely to the virulence of microbial agents. Several recent advances concerning the influence of human genes in chronic viral hepatitis B and C are discussed in this article: a) the associations between human leukocyte antigen polymorphism and viral hepatic disease susceptibility or resistance; b) protective alleles influencing hepatitis B virus (HBV) and hepatitis C virus (HCV) evolution; c) prejudicial alleles influencing HBV and HCV; d) candidate genes associated with HBV and HCV evolution; d) other genetic factors that may contribute to chronic hepatitis C evolution (genes influencing hepatic stellate cells, TGF-beta 1 and TNF-alpha production, hepatic iron deposits and angiotensin II production, among others). Recent discoveries regarding genetic associations with chronic viral hepatitis may provide clues to understanding the development of end-stage complications such as cirrhosis or hepatocellular carcinoma. In the near future, analysis of the human genome will allow the elucidation of both the natural course of viral hepatitis and its response to therapy.     

Chronic hepatitis delta virus infection in Van region of eastern Turkey.

BACKGROUND/AIMS: Hepatitis delta virus infection is an important cause of liver morbidity and mortality worldwide. In Eastern Turkey, hepatitis B virus infection is the major cause of chronic liver diseases. We aimed to research the role of hepatitis delta virus infection in chronic liver diseases related to hepatitis B virus infection in the Van region of Eastern Turkey. METHODS: Serological markers of hepatitis B virus and hepatitis delta virus infection [HBsAg, HbeAg, Anti-HBe and Anti- hepatitis delta virus total (IgM+IgG)] were determined by ELISA test in patients with chronic hepatitis and cirrhosis. Serum hepatitis B virus DNA was determined by polymerase chain reaction (PCR) method in chronic hepatitis B patients. RESULTS: Hepatitis delta virus infection was detected in 5% (7/138) of asymptomatic hepatitis B virus carriers, in 16% (24/148) of chronic hepatitis B patients and in 45% (34/75) of cirrhotic hepatitis B virus patients. hepatitis delta virus infection showed a three-fold increase in chronic hepatitis (p<0.01) and nine-fold increase in cirrhosis (p<0.001) compared to hepatitis delta virus carriers. Also, it was three times more frequent in cirrhosis (p<0.001) compared to chronic hepatitis. Chronic hepatitis delta virus infection was equally distributed between sexes in patients with chronic hepatitis B virus infection, whereas chronic hepatitis B virus infection alone was three times more frequent in males (p<0.001). Mean ages of hepatitis delta virus carriers, chronic hepatitis D and hepatitis delta virus cirrhosis patients were 30.7+/-8 (14-65), 36+/-13 (19-70) and 44 +/-16 (25-55), respectively. CONCLUSIONS: The higher prevalence of hepatitis delta virus infection in more severe form of hepatitis B virus infection suggests that hepatitis delta virus infection increases the severity of chronic hepatitis B virus infection in the Van region. hepatitis delta virus infection remains a second major cause of chronic liver diseases in Eastern Turkey in spite of its decreasing prevalence in Western countries and in Western Turkey.     

Hepatitis b vaccination

Hepatitis B virus (HBV)infection is a major cause of chronic hepatitis and cirrhosis,with an estimated 350 million people worldwide infected with the virus.Despite continuing advances in antiviral therapy,a cure for chronic HBV infection is considered an elusive goal.Thus,primary prevention by immunization with HBV vaccines remains the most effective means to control the transmission of HBV infection.     

Cell Culture Models for the Study of Hepatitis D Virus Entry and Infection

Chronic hepatitis D is one of the most severe and aggressive forms of chronic viral hepatitis with a high risk of developing hepatocellular carcinoma (HCC). It results from the co-infection of the liver with the hepatitis B virus (HBV) and its satellite, the hepatitis D virus (HDV). Although current therapies can control HBV infection, no treatment that efficiently eliminates HDV is available and novel therapeutic strategies are needed. Although the HDV cycle is well described, the lack of simple experimental models has restricted the study of host–virus interactions, even if they represent relevant therapeutic targets. In the last few years, the discovery of the sodium taurocholate co-transporting polypeptide (NTCP) as a key cellular entry factor for HBV and HDV has allowed the development of new cell culture models susceptible to HBV and HDV infection. In this review, we summarize the main in vitro model systems used for the study of HDV entry and infection, discuss their benefits and limitations and highlight perspectives for future developments.     

Hepatitis B virus replication in acute hepatitis B, acute hepatitis B virus-hepatitis delta virus coinfection and acute hepatitis delta superinfection

To evaluate the effect of hepatitis delta virus on the level of replication of hepatitis B virus and to assess the clinical significance that such an effect might have on the final outcome of the infection, the serological profile of hepatitis B virus DNA was investigated in 153 patients with acute or chronic hepatitis B virus infection with or without associated delta infection. Serum hepatitis B virus DNA was detected in 57% of patients with acute hepatitis B, 67% of those with acute hepatitis B virus-hepatitis delta virus coinfection and 25% of HBsAg carriers with hepatitis delta virus superinfection during the first week after the onset of symptoms. Patients with acute hepatitis B and those with acute hepatitis B virus-hepatitis delta virus coinfection did not differ significantly with respect to the serological profile of hepatitis B virus DNA and final clinical outcome. Within the group of HBsAg carriers with hepatitis delta virus superinfection, all patients who were initially negative for hepatitis B virus DNA developed chronic hepatitis delta virus infection, whereas 3 of the 4 patients with active hepatitis B virus infection at the time of superinfection showed transient inhibition of hepatitis B virus replication followed by termination of hepatitis delta virus infection in two patients. Therefore, although delta virus may inhibit the replication of hepatitis B virus among chronic HBsAg carriers, this effect is not readily apparent among patients with hepatitis B virus-hepatitis delta virus coinfection.     

A Review of Hepatitis B Virus and Hepatitis C Virus Immunopathogenesis

Despite the advances in therapy, hepatitis B virus (HBV) and hepatitis C virus (HCV) still represent a significant global health burden, both as major causes of cirrhosis, hepatocellular carcinoma, and death worldwide. HBV is capable of incorporating its covalently closed circular DNA into the host cell’s hepatocyte genome, making it rather difficult to eradicate its chronic stage. Successful viral clearance depends on the complex interactions between the virus and host’s innate and adaptive immune response. One encouraging fact on hepatitis B is the development and effective distribution of the HBV vaccine. This has significantly reduced the spread of this virus. HCV is a RNA virus with high mutagenic capacity, thus enabling it to evade the immune system and have a high rate of chronic progression. High levels of HCV heterogeneity and its mutagenic capacity have made it difficult to create an effective vaccine. The recent advent of direct acting antivirals has ushered in a new era in hepatitis C therapy. Sustained virologic response is achieved with DAAs in 85–99% of cases. However, this still leads to a large population of treatment failures, so further advances in therapy are still needed. This article reviews the immunopathogenesis of HBV and HCV, their properties contributing to host immune system avoidance, chronic disease progression, vaccine efficacy and limitations, as well as treatment options and common pitfalls of said therapy.