肝炎、肝硬化、肝癌患者外周血TGF-β1的检测

转化生长因子 β是一个能调节多种细胞分化、增殖、迁移及细胞外基质合成与降解的多功能细胞因子。近年来 ,它在肝硬化的形成过程中的作用、在肝癌发病中的作用以及对肝癌的诊断价值受到关注 ,我们用酶联免疫法 (ＥＬＩＳＡ)测定了 119例急、慢性肝炎、肝硬化、肝癌患者血清ＴＧＦ β1 的含量 ,并以健康人作对照 ,以了解其临床意义。结果 :ＴＧＦ β1 水平急性肝炎组 (8.11ｎｇ Ｌ± 4 .19ｎｇ Ｌ)、慢性肝炎组 (7.73ｎｇ Ｌ± 3.2 7ｎｇ Ｌ)、肝癌组 (11.78ｎｇ Ｌ± 4 .87ｎｇ Ｌ) ,均高于对照组 (4.6 2ｎｇ Ｌ± 2 .72ｎｇ Ｌ) (Ｐ <0 .0…     

139例恶性肿瘤患者外周血自然杀伤细胞活性的研究

本研究采用细胞介导微量细胞毒测定法检测139例恶性肿瘤患者和355例健康个体外周血自然杀伤细胞(NK细胞)对用~(125)IUdR标记的K562靶细胞的细胞毒直接杀伤效应。结果表明,肿瘤患者NK细胞活性显著低于健康个体,其中,肝胆肿瘤和晚期肿瘤患者NK活性降低尤为显著,临床治愈者NK活性恢复到正常人水平。不同临床阶段肿瘤患者经过肿瘤手术切除以及药物加放射线治疗好转者NK活性均显著升高。健康个体随着年龄增长NK活性下降,说明非特异免疫监视能力减弱与肿瘤的发生、发展关系密切。     

乙型肝炎肝硬化患者病毒基因型与特异性、非特异性CTL的关系和意义

目的 探讨乙型肝炎肝硬化患者不同HBV基因型与外周血HBV特异性、非特异性细胞毒性T淋巴细胞（CTL）的关系和意义.方法 91例乙型肝炎肝硬化患者作HBV基因型检测,比较B、C基因型感染者之间HBV特异性、非特异性CTL的差别,并探讨其临床意义.结果 91例乙型肝炎肝硬化患者中,C基因型55例（60.44%）,B基因型35例（38.46%）,B、C混合型1例（1.1%）,C基因型人白细胞抗原（HLA）-A2阳性27例（49.09%）,HBV特异性CTL（0.18%±0.03%）,B基因型HLA-A2阳性18例（51.43%）,HBV特异性CTL（0.38%±0.04%）,高于C基因型,t=5.01,P＜0.01,非特异性CTL：C基因型（11.87%±1.50%）,B基因型（11.90%±1.51%）,t=0.14,P＞0.05.HBV DNA水平：C基因型[（6.01 ±0.81）log10拷贝/ml],高于B基因型[（5.01 ±0.54）log10拷贝/ml],t=5.01,P＜0.01,丙氨酸转氨酶（ALT）：C基因型（251.13 ±131.11）U/L,高于B基因型（121.25±63.21）U/L,t=3.61,P＜0.01,血清总胆红素（TBil 45.61 ±15.11）μmoL/L,高于B基因型（28.11 ±6.25）μmol/L,t=3.05,P＜0.01.结论 与乙型肝炎肝硬化B基因型感染者相比,C基因型感染者的HBV特异性CTL较低,导致HBV DNA水平较高,肝功能损害较重.     

新生儿细菌性肺炎患者外周血自然杀伤细胞的数量变化及其临床意义

目的检测新生儿细菌性肺炎患者外周血总自然杀伤细胞(NK细胞)及其各亚群百分率的变化,探讨NK细胞在其发病中的临床意义。方法采用流式细胞术检测38例新生儿细菌性肺炎患者及18例正常新生儿的总NK细胞及其各亚群占外周血总淋巴细胞百分率,住院天数在10 d以内(含10 d)为A组、住院天数10 d以上为B组;入院时外周血白细胞的数量5.0×109/L或20.0×109/L者为重度感染组,5.0×109/L外周血白细胞数量20.0×109/L者为轻度感染组。结果新生儿细菌性肺炎患者外周血总NK细胞及CD3-CD56negCD16bright百分率低于正常新生儿(P0.01),但NK细胞CD3-CD56bright CD16neg/dim及CD3-CD56dimCD16bright亚群差异无统计学意义。A组CD3-CD56negCD16bright亚群百分率低于正常新生儿(P0.01),而总NK细胞及其他亚群则差异无统计学意义。B组总NK细胞及CD3-CD56negCD16bright亚群百分率低于正常新生儿(P0.01),且B组总NK细胞及各亚群百分率低于A组(P0.05)。重度感染组总NK细胞及其各亚群百分率明显低于轻度感染组,差异有统计学意义(P0.05)。结论新生儿细菌性肺炎患者病情越重住院时间越长,总NK细胞及其各亚群百分率越低。     

肝炎肝硬化患者血清sIL—6R和sgp130变化的研究

为了探讨肝炎肝硬化（ＨＣ）患者血清可溶性白介素６受体（ｓＩＬ－６Ｒ）和可溶性ｇｐ１３０（ｓｇｐ１３０）含量的变化及其临床意义，运用酶联免疫吸附法检测了３４例ＨＣ患者血清ｓＩＬ－６Ｒ和ｓｇｐｌ３０含量。结果表明：①活动性和静止性ＨＣ患者血清ｓＩＬ－６Ｒ和ｓｇｐ１３０水平均高于正常对照（Ｐ＜０．０１），ｓＩＬ－６Ｒ／ｓｇｐ１３０比值ＨＣ患者低于正常人，活动性ＨＣ患者低于静止性ＨＣ患者（Ｐ＜０．０１）；②血清ｓＩＬ－６Ｒ和ｓｇｐ１３０水平之间呈正相关（ｒ＝０．４１７，Ｐ＜０．０５），ｓＩＬ－６Ｒ、ｓｇｐｌ３０水平与血清Ｂｉｌ－Ｔ水平间亦呈正相关（分别为ｒ＝０．４７４，ｒ＝０．４８２，Ｐ＜０．０１），而与血清ＡＬＴ水平无明显相关性（分别为ｒ＝０．１９３，ｒ＝０．１５２，Ｐ＞０．０５）。提示：血清ｓＩＬ－６Ｒ、ｓｇｐ１３０与ＨＣ的病情演变有关     

PCR-RFLP检测肝癌和肝硬化患者乙型肝炎病毒基因型

目前已发现的HBV基因型有A～G 7种。国内外已有一些有关HBV基因型对HBV感染途径以及与HBV感染后肝病进展的报道〔1〕,但至今还没有确切的结论。目前HBV基因型分型方法主要有3种,即全基因测序、PCR RFLP法以及ELISA结合探针杂交的方法。我们以新近提出的PCR RFLP法〔2〕对无症状携带者(asymptomaticcarriers ,AsC)、肝硬化以及肝癌患者3组血清进行HBV基因分型,以探讨HBV基因型与肝硬化、肝癌的发生和发展可能存在的关系。材料和方法研究对象:6 0例AsC为南方医院传染科门诊病人,诊断标准按照1995年第五届全国传染病会议通…     

肝炎后肝硬化患者甲襞微循环的改变及分析

病毒性肝炎患者均存在着不同程度的微循环障碍，尤其是肝硬化病人。为探讨肝炎后肝硬化患者甲襞微循环改变之特点。我们对30例肝炎后肝硬化患者进行了甲襞微循环的临床观察，并与30例健康正常人进行了比较。1资料与方法观察对象：所有病例均来源于本院传染科1997年3月至11月住院病人。30例肝炎后肝硬化病人（肝硬化组）的诊断标准均依据1990年5月全国第六次病毒性肝炎会议（上海）议定的诊断分型标准，其中男18例、女12例，男女之比为1．50：1；年龄20～60岁，平均年龄39．86岁。健康组30例（对照组）均来源于本院职工自愿受试者，其中男17…     

不同基因型慢性乙型重型肝炎患者外周血T细胞亚群的分析

慢性乙型重型肝炎（简称慢重肝）是指在慢性肝炎或肝硬化基础上出现肝组织大块或亚大块坏死,病死率高达50%以上。因其发病机制复杂,至今仍未完全阐明。有研究表明,机体细胞免疫在慢重肝的发生、发展过程中起着重要作用。     

肝炎后肝硬化患者生存质量调查与影响因素分析

目的测量并评价肝炎后肝硬化患者生存质量（QOL）以及影响因素。方法采用SF-36量表,对220例肝炎后肝硬化患者和220例正常对照者进行QOL测量与评价,并对其影响因素进行单因素分析和多因素逐步回归分析。结果肝炎后肝硬化患者SF-36总评分与对照组相比差异有统计学意义。影响肝炎后肝硬化患者QOL的主要因素是性别、Child-Pugh分级、血小板计数（P=0.004、0.013、0.011）。结论肝炎后肝硬化患者生存质量全面下降,Child-Pugh分级、性别与血小板计数为肝硬化患者生存质量的主要影响因素。     

肝炎和肝硬化患者胆囊B超改变的观察与分析

目的研究肝炎肝硬化患者胆囊彩色B超声像图变化，并探讨其临床意义。方法采用彩色超声诊断仪对139例肝炎和肝硬化患者及65例非肝炎体检者进行胆囊超声检查。结果慢性肝炎、重型肝炎、肝硬化患者组与非肝炎对照组彩色B超胆囊异常率比较均差异非常显著（P〈0．01）。慢性肝炎与重型肝炎、肝硬化组之间胆囊异常率也存在明显的差异（P〈0．05）。结论慢性肝病患者胆囊异常并不是胆囊本身炎症所致，胆囊声像图的改变对判断肝脏实质性病变的严重程度及指导临床治疗有一定的作用。     

Activated natural killer cells accelerate liver damage in patients with chronic hepatitis B virus infection

Emerging evidence indicates that natural killer (NK) cells may contribute to liver injury in patients with hepatitis B virus (HBV) infection. Because HBV infection progresses through various disease phases, the cytolytic profiles of peripheral and intrahepatic NK cells in HBV‐infected patients remain to be defined. In this study, we comprehensively characterized intrahepatic and peripheral NK cells in a cohort of HBV‐infected individuals, and investigated their impact on liver pathogenesis during chronic HBV infection. The study population included 34 immune‐clearance (IC) patients, 36 immune‐tolerant (IT) carriers and 10 healthy subjects. We found that the activity of peripheral NK cells from IC patients was functionally elevated compared to IT carriers and controls, and NK cell activation was indicated by an increased expression of CD69, CD107a, interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α. Further analysis showed that the increased activity of both peripheral and hepatic NK cells was correlated positively with liver injury, which was assessed by serum alanine aminotransferase levels (ALT) and the liver histological activity index (HAI). Interestingly, the frequency of peripheral NK cells was reduced in IC patients (especially those with higher HAI scores of 3–4), but there was a concomitant increase in hepatic NK cells. The functionally activated NK cells are enriched preferentially in the livers of IC patients and skew towards cytolytic activity that accelerates liver injury in chronic hepatitis B (CHB) patients.     

慢性乙型肝炎患者外周血树突状细胞功能状态与HBV载量的关系

目的：探讨慢性乙型肝炎（CHB）患者外周血树突状细胞功能状态与HBV载量的关系。方法：采集23例CHB患者和8例健康人的抗凝外周静脉血，分离外周血单个核细胞（PBMCs），在重组人白细胞介素4和重组人粒细胞-巨噬细胞集落刺激因子的作用下培养使DCs增殖、成熟，以间接免疫荧光流式细胞技术分别检测DCs表面CD80、CD86、HLA-DR及ICAM-1的表达；以ELISA法检测DCs培养上清液中IL-12的水平；将培养成熟的DCs与HBsAg共同孵育，用丝裂霉素C处理后再与自体PBMCs共同培养，在培养结束前12小时加入^3H-TDR，收集细胞，以β液闪计数仪测定cpm值；同期用定量聚合酶链反应技术测定CHB患者外周血HBV载量。结果：患者DCs表面CD86、HLA-DR和ICAM-1的表达水平，DCs的抗原提呈能力及其分泌IL-12的水平均显著低于健康对照组；CD80、CD86、HLA-DR及ICAM-1的表达与HBV载量呈显著负相关关系（分别为P〈0．01、P〈0．01、P〈0．001和P〈0．001）；DCs的抗原提呈能力及其分泌IL-12的水平也与HBV载量呈显著负相关关系（分别为P〈0．001和P〈0．01）。结论：CHB患者外周血DCs的成熟和功能存在障碍，DCs的功能状态与血液中HBV的载量密切相关，并可能对HBV的清除产生重要的影响。     

慢性乙型肝炎患者NK细胞水平与HBV DNA的关系

我们将HBV DNA阴性的慢性乙型肝炎(CHB)患者(50例)与HBV DNA阳性的CHB患者(128例)比较NK细胞水平,并进行肝功能的比较,探讨CHB患者的NK细胞水平与HBV DNA的关系.     

HBV基因型与HBV感染慢性化、重症化的关系

目的 探讨HBV基因型与HBV感染后慢性化、重症化的关系.方法 应用型特异性引物聚合酶链反应法,对中国2922例HBV感染者进行HBV基因型检测,比较各临床类型HBV感染者基因型分布差异及各基因型HBV感染者肝功能和病毒学差异.结果 2922例HBV感染者中,基因型B、C、B/C、D分别占15.9%、83.5%、0.41%、0.21%.与慢性肝炎比较急性肝炎B基因型所占比例较高（P=0.003）,肝硬化和肝细胞性肝癌C基因型所占比例较高（P值均为0.000）,慢加急性肝衰竭与慢性肝炎比较基因型分布差异无统计学意义.急性肝炎和慢性肝炎B、C基因型患者HBeAg 阳性率、HBV DNA病毒载量、肝功能生化指标差异无统计学意义.慢加急性肝衰竭、肝硬化、肝细胞性肝癌组C基因型较B基因型患者HBeAg阳性率更高（P值分别为0.000、0.024、0.003）,肝细胞性肝癌C基因型患者HBV DNA病毒载量高于B基因型患者（P=0.025）,慢加急性肝衰竭和肝细胞性肝癌组C基因型较B基因型患者胆碱酯酶更低（P值为0.0004、0.02）.结论 中国HBV感染者的HBV基因型以B、C基因型为主,少量的B/C、D基因型;C基因型较B基因型HBV感染者更易发生慢性化和进展为肝硬化和肝细胞性肝癌,但未观察到基因型对慢加急性肝衰竭发生的差异.急性和轻症HBV感染者B、C基因型未显示对病情的明显影响,但重症和终末期HBV感染者C基因型较B基因型患者HBeAg阳性率、HBV DNA病毒载量更高,肝功能损害更严重.     

HBV基因型与HBV感染慢性化、重症化的关系

Objective To explore the association between HBV genotype and chronic/severe liver disease with HBV infection in Chinese patients.Methods Serum samples were collected from 2922 patients with HBV infection.HBV genotyping was performed with type-specific primers polymerase chain reaction,and the virological and biochemical markers were detected,which differences in the genotypes between various clinical types of HBV infection and liver function and virological markers between various HBV genotyping were analyzed.Results The genotype B,C,BC combinations,D of 2922 patients with HBV infection accounted for 15.9%,83.5%,0.41%,0.21% respectively.The ratio of genotype B in acute hepatitis group was higher(P=0.003),which the ratio of genotype C in the cirrhosis group and the hepatocellular carcinoma group was higher(P=0.000,0.000).The difference in ratio of genotype C was not statistically significant between acute-on-chronic liver failure group and chronic hepatitis group.HBeAg-positive rate,viral load and liver function markers of B,C genotype group in acute hepatitis group and chronic hepatitis group were not significant different.HBeAg-positive rates of genotype C in acute-on-chronic liver failure group,cirrhosis group,hepatoeellular carcinoma group were higher than that of genotype B(P=0.000,0.024,0.003).Viral load of genotype C in hepatocellular carcinoma group was higher than that of genotype B(P=0.025).Cholinesterase levels of genotype C in the acute-on-chronic liver failure group and the hepatocellular carcinoma group was lower than that of genotype B(P=0.0004、0.02).Conclusion There were HBV genotype B,C,B/C combinations and D in Chinese patients with HBV infection,with genotype B and C being the major ones.Compared with HBV genotype B,genotype C in Chinese patients with HBV infection was more likely to chronic infection,evolved to cirrhosis and hepatocellular carcinoma, but genotype difference was not observed in occurrence of acute-on-chronic liver failure.Genotype was not significant effect in acute and chronic hepatitis B,but HBeAg-positive rate/viral load was higher and liver damage was more severe in severe and end-stage genotype C HBV infection patients.     

HBV基因型与HBV感染慢性化、重症化的关系

Objective To explore the association between HBV genotype and chronic/severe liver disease with HBV infection in Chinese patients.Methods Serum samples were collected from 2922 patients with HBV infection.HBV genotyping was performed with type-specific primers polymerase chain reaction,and the virological and biochemical markers were detected,which differences in the genotypes between various clinical types of HBV infection and liver function and virological markers between various HBV genotyping were analyzed.Results The genotype B,C,BC combinations,D of 2922 patients with HBV infection accounted for 15.9%,83.5%,0.41%,0.21% respectively.The ratio of genotype B in acute hepatitis group was higher(P=0.003),which the ratio of genotype C in the cirrhosis group and the hepatocellular carcinoma group was higher(P=0.000,0.000).The difference in ratio of genotype C was not statistically significant between acute-on-chronic liver failure group and chronic hepatitis group.HBeAg-positive rate,viral load and liver function markers of B,C genotype group in acute hepatitis group and chronic hepatitis group were not significant different.HBeAg-positive rates of genotype C in acute-on-chronic liver failure group,cirrhosis group,hepatoeellular carcinoma group were higher than that of genotype B(P=0.000,0.024,0.003).Viral load of genotype C in hepatocellular carcinoma group was higher than that of genotype B(P=0.025).Cholinesterase levels of genotype C in the acute-on-chronic liver failure group and the hepatocellular carcinoma group was lower than that of genotype B(P=0.0004、0.02).Conclusion There were HBV genotype B,C,B/C combinations and D in Chinese patients with HBV infection,with genotype B and C being the major ones.Compared with HBV genotype B,genotype C in Chinese patients with HBV infection was more likely to chronic infection,evolved to cirrhosis and hepatocellular carcinoma, but genotype difference was not observed in occurrence of acute-on-chronic liver failure.Genotype was not significant effect in acute and chronic hepatitis B,but HBeAg-positive rate/viral load was higher and liver damage was more severe in severe and end-stage genotype C HBV infection patients.     

HBV-ACLF患者外周血和肝脏NK细胞的表达频率及功能与肝损伤的相关性

目的 探讨HBV相关慢加急性肝衰竭(HBV-ACLF)患者外周血和肝组织自然杀伤(NK)细胞的表达频率及功能与肝损伤的相关性.方法 利用多色流式技术检测14例HBV-ACLF患者和15例HBV-CHB(慢性乙型肝炎)患者外周血NK细胞(CD3-CD56+)的表达频率和NK细胞表面CD107a的表达,胞内细胞因子染色技术检测NK细胞分泌IFN-γ的水平.收集20例HBV-ACLF患者、10例轻度CHB患者肝组织穿刺标本,利用免疫组织化学双染技术检测肝组织中CD3和CD57抗原的表达.分析轻度CHB和HBV-ACLF患者肝脏NK细胞的表达频率及与肝损伤程度(TBIL水平)的相关性.结果 HBV-ACLF患者与轻度CHB患者外周血NK细胞的表达频率和IFN-γ的表达差异均无统计学意义(12.7％ ±5.3％ vs 9.6％±3.3％和4.52％ ±2.52％ vs 9.06％±7.6％,P均＞0.05),HBV-ACLF患者外周血CD107a表达(NK细胞的杀伤活性)要显著强于轻度CHB患者(52.1％±18.9％ vs 30.9％ ±12.4％,P＜0.05).HBV-ACLF患者肝组织中CD57+NK细胞的表达频率显著高于轻度CHB患者(95.1±21.3/低倍镜视野 vs 9.5 ±10.6/低倍镜视野,P＜0.01).肝脏CD57+NK细胞的表达频率与TBIL水平显著正相关,相关系数为0.936.结论 外周血NK细胞杀伤活性显著增强和肝脏中CD57+NK细胞大量募集可能是导致HBV-ACLF免疫性肝损伤加剧,肝细胞大量凋亡和坏死的重要因素.     

慢性乙型肝炎患者、HBV携带者及急性自限性HBV感染者外周血调节性T细胞的差异及意义

目的比较慢性乙型肝炎患者、HBV携带者、急性自限性HBV感染者与正常对照之间外周血调节性T细胞（Treg）比例的差异，分析HBV感染后不同临床转归与Treg的关系，为慢性乙型肝炎的治疗提供新的线索。方法选取2004年2月至10月在我院肝炎门诊就诊的慢性乙型肝炎患者28例、HBV携带者23例、急性自限性HBV感染者19例以及健康献血员14例，使用流式细胞仪检测其外周血Treg的比例，分析其差异及临床意义。结果慢性乙型肝炎组外周血Treg占CD4^＋T细胞的比例为7．2％±3．1％，较HBV携带者组、急性自限性HBV感染者组及正常对照组增高；而HBV携带者组、急性自限性HBV感染者组及正常对照组之间Treg比例差异无统计学意义。结论Treg在HBV感染后慢性化的过程中可能发挥了一定的作用。     

HBeAg阴性慢性乙型肝炎患者血清病毒载量与肝组织学改变的关系

Objective To investigate the relationship between serum HBV DNA loads and liver histology damage in the patients with HBeAg-negative chronic hepatitis B.Methods The retrospective study was performed.The 514 patients were divided into two groups according to the HBeAg status and the HBeAg positive group was as control.The relationship among HBV DNA loads,live histological inflammation grades and fibrosis stages was analyzed.Results The HBV DNA loads in HBeAg-negative group and HBeAg-positive group were(5.38±1.27)log10 copies/ml and(6.80±1.18)log10 copies/ml respectively(P<0.001).The inflammation grades and fibrosis stages of liver tissues in HBeAg-negative group were all significantly higher than those in HBeAg-positive group(P<0.001).In HBeAg-negative group,HBV DNA loads displayed a positive correlation with the inflammation grades and fibrosis stages of liver tissues(P<0.001).Conclusion In the patients with HBeAg-negative chronic hepatitis B,HBV viral loads are lower than those with HBeAg-positive chronic hepatitis B,and HBV viral loads display a positive correlation with liver the inflammation grades and fibrosis stages of liver tissues.     

HBeAg阴性慢性乙型肝炎患者血清病毒载量与肝组织学改变的关系

目的 探讨HBeAg阴性慢性乙型肝炎患者血清HBV DNA水平与肝组织损害的关系.方法 以HBeAg阳性慢性乙型肝炎病例为对照,回顾分析HBeAg阴性慢性乙型肝炎患者血清HBVDNA水平与肝组织病理炎症分级、纤维化分期之间的关系.结果 HBeAg阴性与阳性组HBV DNA 平均含量分别为（5.38±1.27）log10拷贝/ml和（6.80±1.18）log10拷贝/ml,差异有统计学意义（P〈0.01）.与HBeAg阳性组比较,HBeAg阴性组肝组织炎症分级及纤维化分期较高（P〈0.01）.HBeAg 阴性患者HBV DNA水平与肝组织炎症分级及纤维化分期呈正相关（P〈0.01）.结论 HBeAg阴性慢性乙型肝炎病毒载量低,乙肝病毒载量与肝损害呈正相关.