HDAg与HBsAg／HBcAg在丁型肝炎病人肝组织中的表达

研究HDAg、HBsAg和HBcAg在丁型肝炎病人肝组织中表达及关系 ,探讨HDV致病机理。应用免疫组化双重染色及连续切片技术 ,检测 79例丁型肝炎病人肝组织HDAg、HBsAg和HBcAg表达 ,以 5 2例乙型肝炎作对照。丁型肝炎HBsAg、HBcAg检出率 (81%、71% )较乙型肝炎 (94%、92 % )低 (P <0 0 5或 0 0 1)。HDAg以肝细胞核表达为主 ,HBsAg以肝细胞浆表达为主 ,HDAg和HBsAg表达强度及阳性细胞分布呈一致性 ,均与肝组织炎症活动和病理损害程度相关 (P <0 0 1)。HBcAg以肝细胞核表达为主 ,HBcAg阳性细胞明显少于HDAg阳性细胞。HDV感染可抑制HBV抗原表达 ;在HDV致病机制中既有HDV的直接细胞毒性作用 ,也有HBV和HDV的协同作用。     

丁型肝炎患者肝组织HDAg和HBsAg/HBcAg的免疫组化检测

目的 探讨HDAg和HBsAg/HBcAg在丁型肝炎患者肝组织中表达及关系。方法 应用免疫组化双重染色,检测79例丁型肝炎患者肝组织HDAg、HBsAg和HBcAg表达,以52例乙型肝炎作对照。结果 丁型肝炎HBsAg、HBcAg检出率(81％、71％)较乙型肝炎(94％、92％)低(P<0.05或0.01)。HDAg以肝细胞核表达为主,HBsAg以肝细胞浆表达为主,HDAg和HBsAg表达强度及阳性细胞分布呈一致性,且均与肝组织的炎症活动和病理损害程度相关(P<0.01)。HBcAg以肝细胞核表达为主,阳性细胞主要呈单个细胞或点状分布,且HBcAg阳性细胞明显少于HDAg阳性细胞。结论 HDV感染会抑制HBV病毒抗原(HBcAg)表达;HDV致病机制中既有HDV的直接细胞毒性作用,也有HBV和HDV的协同作用。     

Fas/FasL在丁型肝炎发病机理中的作用

目的检测丁型肝炎病人肝组织Fas/FasL和HDAg表达,了解Fas/FasL在丁型肝炎致病机理中的作用。方法采用免疫组化单、双标记技术,检测48例丁型肝炎病人肝组织Fas、FasL和HDAg表达,以54例乙型肝炎作疾病对照。结果 Fas以肝细胞浆表达为主,HDAg以肝细胞核和胞浆表达为主,二抗原表达及分布呈一致性。FasL主要表达在浸润淋巴细胞浆、肝细胞核,与HDAg表达及分布不全一致,丁型肝炎组Fas、FasL检出率及表达强度较对照组高,三成分在各型肝炎中的表达强度有显著性差别意义。结论 Fas、FasL和HDAg均与肝组织炎症活动和病理损害相关,HDV感染可诱导肝细胞大量表达Fas,CTL通过Fas/FasL途径介导的肝细胞凋亡与HDV致病可能有关。     

丁型肝炎患者肝组织中Bcl-2、Bax和肝细胞凋亡表达

目的 探讨bcl-2、bax及肝细胞凋亡在丁型肝炎发病机理中的作用。方法 采用免疫组织化学单、双标记染色和TUNEL技术、检测77例丁型肝炎患者肝组织HDAg、bcl-1、bax及肝细胞凋亡表达，以67例乙型肝炎作对照，结果 bcl-2和bax均以肝细胞浆表达为主。HDAg以肝细胞核表达为主。HDAg和Bax与凋亡细胞表达及分布有相关性，三成分在各型肝炎中的表达强度差异有显著意义（P＜0.05）。结论 HDAg、bax和肝细胞凋亡表达强度和阳性细胞分布均与肝组织炎症活动及病理损害程度相关，HDV感染可诱导肝细胞表达bax，增强肝细胞凋亡，这一机制在丁型肝炎发病机理中可能有一定重要作用。     

丁型肝炎病人肝组织HDAg和 Fas表达及其相互关系

目的 研究丁型肝炎病人肝组织Fas和HDAg表达及其相互关系,了解Fas在HDV致病机制中的作用。方法 应用免疫组化单、双标记技术,检测48例丁型肝炎病人肝组织Fas、HDAg表达,以54例乙型肝炎病人肝组织Fas表达作对照。结果 Fas以肝细胞浆表达为主,HDAg以肝细胞核和胞浆表达为主,二抗原表达及分布呈一致性。各型肝炎中Fas和HDAg表达有统计学差别,两种抗原的分布和表达强度与肝细胞炎症活动和病理损害程度相关。结论 Fax和HDAg表达及分布密切相关,与肝组织炎症活动和病理损害相关,此提示HDV感染可诱导肝细胞表达Fas,Fas及其所介导的肝细胞凋亡在HDV致病机制中可能有重要作用。     

HBV和HDV感染患者肝组织中HDAg与Bcl-2、Bax和Bak表达的关系

目的探讨bcl-2、bax、Bak在乙型肝炎病毒和丁型肝炎病毒重叠感染患者病情加重机制中的作用.方法采用免疫组化单、双标记染色技术,检测77例伴HDV感染的乙型肝炎患者肝组织中HDAg、bcl-2、bax和Bak表达.以HDV阴性的67例乙型肝炎作对照.结果bcl-2、Bax和Bak均以肝细胞浆表达为主.HDAg以肝细胞核表达为主.HDAg与Bax和Bak表达及分布有相关性,它们在各型肝炎中的表达强度有显著性差异(P＜0.05).结论HDAg、bax、Bak表达强度和阳性细胞分布均与肝组织炎症活动及病理损害程度相关,HDV感染可诱导肝细胞表达bax和Bak,增强肝细胞凋亡,这一机制在伴HDV感染的乙型肝炎患者病情加重中可能起一定的作用.     

丁型肝炎患者肝组织中Fas/FasL和肝细胞凋亡表达

目的探讨Fas/FasL及肝细胞凋亡在丁型肝炎患者肝组织中的表达及作用.方法采用免疫组化双重染色和TUNEL技术,检测79例丁肝患者肝组织HDAg,Fas/FasL表达,以及肝细胞凋亡,以54例乙型肝炎作对照.结果Fas以肝细胞浆表达为主,HDAg以核浆型表达为主,二抗原表达及分布有相关性.FasL主要表达在浸润淋巴细胞浆、肝细胞核,与HDAg表达及分布不全一致.HDAg,Fas/FasL和肝细胞凋亡在各型肝炎中的表达强度有显著性差别意义.结论HDV感染可诱导肝细胞Fas/FasL表达,增强Fas/FasL途径介导的肝细胞凋亡,这一机制在丁型肝炎发病机制中可能有一定的重要作用.     

伴HDV感染的乙型肝炎患者的临床特征

目的　通过对丁型肝炎病毒（HDV）感染的乙型肝炎患者临床特点分析，了解HDV感染特征和HDV致病机理。方法　对合并HDV感染的507例乙型肝炎患者各临床类型肝炎的发生、预后、临床表现、生物化学指标、肝炎病毒标志物等作统计分析，以213例单纯HBV感染的乙型肝炎患者作对照。结果　HDV感染后重型肝炎、肝硬化的发生率和病死率、及发生出血、腹水、并发症和ALT反复增高及增高幅度均较HDV阴性者高（P＜0.01或P＜0.05），重度慢性肝炎和重型肝炎患者的生物化学指标异常也较对照组明显（P＜0.01）。血清HBeAg检出率降低（P＜0.01）。急性肝炎、重型肝炎和肝硬化HDAg（+）、HBeAg（-）表达高于HDAg。HBeAg均阳性者（P＜0.01或P＜0.05）。结论　HDV感染后重度慢性肝炎、重型肝炎和肝硬化的发生率高，预后差；HDV感染可抑制HBV复制或HBeAg表达；HDV的直接细胞毒性作用在急性肝炎中可能起主要致病作用，在合并有HDV感染的乙型肝炎患者病情加重、病死率增高和慢性化过程中，HDV可能起主要促进作用。     

树鼩实验感染丁型肝炎病毒后肝内抗原表达状态

目的 研究树鼩实验感染人丁型肝炎病毒的可能性。方法 用免疫组化方法,检测树鼩肝组织丁型肝炎病毒抗原(HDAg),乙型肝炎病毒表面抗原HBsAg),采用原位杂交方法检测部分动物肝内HDV RNA。结果 35只动物,HDV/HBV同时感染组和重叠感染组HDAg阳性率分别为94.5％(21╱22)和84.6％(11/13);HDAg在肝内主要定位于肝细胞,在肝小叶呈灶状或片状分布,肝内持续时间在同时感染组和重叠感染组稍有不同,前者多持续3～4周,后者则可长达12周以上;部分动物肝组织细胞浆或细胞核HDV RNA阳性。结论 人HDV可感染树鼩,树鼩可成为丁型肝炎研究的动物模型。     

Bcl-2/bax、Bak介导的肝细胞凋亡在丁型肝炎病情重型化机制中的作用

目的　探讨Bcl 2 /bax、Bak及其介导的肝细胞凋亡在病情重型化机制中的作用。方法　采用刊TUNEL技术和免疫组化单、双标记染色 ,检测 77例丁肝病人肝组织中HDAg、bcl 2、bax和Bak表达及肝细胞凋亡情况。以HDV阴性的 67例乙型肝炎作对照。结果　Bcl 2、bax和Bak均以肝细胞浆表达为主。HDAg以肝细胞核表达为主。HDAg、bax和Bak与肝细胞凋亡表达及分布有相关性 ,四成分在各型肝炎中的表达强度有显著性差别意义 (P <0 .0 5 )。结论　HDAg、bax、Bak和肝细胞凋亡表达强度和阳性细胞分布均与肝组织炎症活动及病理损害程度相关 ,HDV感染可诱导肝细胞表达bax和Bak ,增强肝细胞凋亡 ,这一机制在丁型肝炎发病机理中可能有一定重要作用     

Hepatitis D virus (delta agent) superinfection in an endemic area of hepatitis B infection: immunopathologic and serologic findings

In 86 Chinese patients with histologically proven hepatitis B surface antigen (HBsAg) positive chronic hepatitis and serum alanine aminotransferase levels exceeding 200 U/l, antibody to hepatitis D antigen (HDAg) was detected more frequently in sera from hepatitis B e antigen (HBeAg) negative patients (11/35, 31.4%) than in HBeAg positive (4/51, 7.8%) patients (p less than 0.02). 10 liver biopsy specimens (76.9%) from 13 chronic hepatitis B patients with superimposed hepatitis D virus (HDV) infection, showed positive staining for HDAg in their hepatocytes. Neither HBsAg nor hepatitis B core antigen (HBcAg) was found in the liver in 12/13 patients with superimposed HDV infection. However, in liver biopsy specimens from 42 patients without HDV superinfection, HBsAg was stained positively in 41 patients (97.6%), and HBcAg in 24 patients (47.1%). Using dot blot hybridization technique, serum hepatitis B virus (HBV) DNA was detected in 62.1% (41/66) of patients without HDV superinfection, while it was detected only in 10.0% (1/10) of patients who had HDV superinfection. It is concluded that HDV superinfection plays a significant role in Taiwan in HBeAg negative chronic hepatitis B patients with clinical "exacerbation". The data show clear evidence of HDV interfering with the replication of HBV.     

Intrahepatic expression of hepatitis B core and surface antigens in chronic hepatitis delta-virus infection.

To evaluate the interference of hepatitis B virus (HBV) protein expression in the liver in chronic hepatitis delta-virus (HDV) infection, the intrahepatic expression of hepatitis B core and surface antigens (HBcAg and HBsAg) was studied in 36 HBsAg carriers who were seropositive for anti-HDV and in 36 anti-HDV negative controls [18 with serum hepatitis B e-antigen (HBeAg) and 18 with anti-HBe]. Of 18 HBeAg-positive patients with anti-HDV, 12 had HDV antigen (HDAg) in the liver. HBcAg was positive in 66.7% (8/12) of the HbeAg-positive patients with HDAg in the liver, and in 94.4% (17/18) of controls (p = 0.14). The distribution of HBcAg was exclusively cytoplasmic in 75% (6/8) of HDV-infected patients, but was mixed nuclear and cytoplasmic in 70.6% (12/17) of the controls. The prevalence and quantitative expression of HBcAg in the nucleus, but not in the cytoplasm, were significantly decreased in chronic HDV infection. HBsAg was positive in 91.6% (11/12) of HBeAg-positive patients with HDV infection and in all controls. Membranous expression of HBsAg was detected less frequently in HDV-infected patients than in controls (7/12 vs. 17/18, p = 0.05), while the prevalence and quantitative expression of HBsAg in the cytoplasm showed little or no difference. HDAg was detected in all of the anti-HBe-positive patients with anti-HDV. Of these, none had HBcAg detectable in the liver, nor did controls, while HBsAg was detected exclusively in the cytoplasm in 94.4% (17/18). The prevalence and quantitative expression of HBsAg in the cytoplasm was not different for HDV-infected patients or controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Course of hepatitis B and D virus infection in auxiliary liver grafts in hepatitis B-positive patients : A light-microscopic and immunohistochemical study

Four patients who received an auxiliary partial liver graft for decompensated liver cirrhosis due to hepatitis B (HBV), associated in two cases with hepatitis D virus (HDV) superinfection, were studied. The sequential appearance of hepatitis B and D antigens in the grafts was investigated in serial liver biopsies by immuno-histochemical methods and compared with the viral antigenic profiles of the host livers. The histological changes in the liver grafts were studied in relation to the viral expression patterns. One week after transplantation, expression of HBsAg was already apparent in two grafts. HBcAg was found in the graft of the only patient with HBcAg in the host liver. HDAg was expressed in the grafts of both patients with HDV superinfection; in one of these cases HDAg was present without HBsAg. At 3 months, viral antigen expression was maximal. Expression of HBsAg and HBcAg in the grafts of the two HDV-positive patients was, however, less extensive than in the two HBV-positive patients. All patients developed a mild lobular hepatitis, histologically demonstrated between the 47th and 107th posttransplantation day. In the two HBV-positive, HDV-negative patients, cirrhotic transformation of the graft occurred within 1 year. In the HDV-positive patients only a mild chronic active hepatitis with slight or moderate fibrosis was observed after 1 year. We conclude that recurrence of HBV and HDV infection in auxiliary liver grafts is demonstrable within 1-3 weeks. HBV infection in liver grafts may be a rapidly progressive disease. Coinfection with HDV does not aggravate the acute hepatitis and may even suppress the progression of chronic HBV.     

HDV感染后乙型肝炎患者血清肝炎病毒标志物的变化

目的　分析HDV感染患者血清病毒性肝炎标志物的变化和意义 ,探讨HDV致病机理。方法　对 469例HDV阳性乙型肝炎患者常见各类型病毒性肝炎血清标志物的变化等作统计分析 ,以 2 13例HDV( -)乙型肝炎患者作对照。结果　HDV感染后血清HBeAg检出率降低 (P <0 .0 1)。在HDV ( +)HBVDNA( -)组 ,HBeAg( -)的机会大 (P <0 .0 1)。在急性肝炎、重型肝炎和肝硬化患者HDAg( +)HBeAg( -)为主要血清病毒表现形式 (P <0 .0 1或 0 .0 5 )。HDV感染后合并其它肝炎病毒感染率高于乙型肝炎组。结论　HDV感染可抑制HBV复制或HBeAg表达 ,混合感染HDV的乙型肝炎中HDV的直接细胞毒性作用可能起主要致病作用。重叠感染HDV的乙型肝炎患者其病情重、病死率高和容易慢性化。     

HBsAg、HBcAg在慢性乙型肝炎肝细胞内的表达及临床意义

目的 探讨HBsAg、HBcAg在慢性乙型肝炎(CHB)患者肝细胞内的表达,及其与血浆HBVDNA定量、肝组织病理和临床间的关系。 方法 采用PCR检测351例CHB患者血浆HBV DNA定量,肝穿刺活检,采用免疫组织化学技术观察肝细胞内HBsAg、HBcAg的表达。 结果 在CHB患者肝细胞内HBsAg和HBcAg阳性表达率分别为92.3％和76.9％。HBcAg浆膜型(75.6％)和胞核型(24.4％)分别见于肝组织炎症较活跃和较静止期CHB。HBsAg表达强度与血浆HBV DNA定量呈较低正向关联(rp=0.24,P=0.0129)、与肝组织炎症和纤维化呈较低负向关联(rp=-0.22,P=0.0279和rp=-0.23,P=0.0186)。HBcAg的表达强度随着血浆HBV DNA定量的增加而增加,呈较强正向关联(rp=0.52,P<0.0001),随着肝组织炎症和纤维化程度的加重而减弱,呈较强的负向关联(rp=-0.33,P<0.0001和rp=-0.34,P<0.0001)。 结论 在CHB肝组织免疫损伤的免疫应答中,HBcAg是靶抗原,HBsAg不一定是靶抗原。HBsAg是筛查HBV感染的较敏感指标,HBcAg是评价HBV复制程度的较可靠指标。     

乙丁型肝炎病毒感染树鼠句肝组织Fas和ICE的表达

目的探讨乙型并丁型肝炎病毒感染树鼠句肝组织中Fas和ICE表达与HDV感染之间的关系。方法采用免疫组织化学技术对45份HDV/HBV感染树鼠句肝组织中HDAg、Fas和ICE的表达进行了检测。结果45份肝组织中有39份可检出Fas(阳性率86.7%),有43份可检出ICE(阳性率95.6%)。Fas和ICE在肝细胞质和(或)膜上表达,以肝细胞质内表达为主。HDAg表达与Fas和ICE表达之间有显著相关性(χ2值为29.2和36.2,P＜0.01),HDAg表达越强,Fas和ICE表达也越强。结论肝细胞内的HDAg表达可诱导Fas和ICE的表达。