HBV、HCV在原发性肝癌发生中的相互作用研究

为了解河南省原发性肝癌（PHC）发生中HBV、HCV的相互作用，我们应用ELISA法和PCR法对PHC患者及其1：1对照进行了HBV标志物（HBVM）和HCV标志物（HCVM）检测。结果：PHC患者HBVM阳性率为81．25％，对照组HBVM阳性率为9．60％，P＜0.01，OR=70（25．36，193．23）；PHC患者HCVM阳性率为19．79%，对照组HCVM阳性率为8.33％，P＜0.05，OR＝2．57（1．11，5．95）；PHC患者HBVM、HCVM双重阳性率为18．75％，对照组双重阳性率为1.04％，将HBVM和（或）HCVM阳性看成不同的暴露等级与HBVM和HCVM均阴性组进行比较，得到HBV和HCV双重感染时的OR值为83.65，明显高于两者分别感染的OR值（34．85和1．58）之积。结果提示：HBV、HCV在PHC的发生中有显著的病因协同作用。     

乙型肝炎病毒感染与B细胞型非霍奇金淋巴瘤的关系．

目的探讨B细胞型非霍奇金淋巴瘤（NHL）与乙型肝炎病毒（HBV）之间的关系。方法统计2003年1月至2009年12月住院的284例B细胞型NHL患者的乙肝5项标志物阳性率,并与同期住院的大肠癌患者作比较。结果B细胞型NHL以18—39岁和Ⅲ一Ⅳ期患者乙型肝炎表面抗原（HBsAg）阳性率较高,分别为42．6％（26／61）和37．0％（50／135）,分别与其他年龄段及I一Ⅱ期患者比较,差异均有统计学意义（x。值分别为7．573和6．874,P值分别为0．023和0．009）;B细胞型NHL患者HBsAg、乙型肝炎e抗原（HBeAg）的阳性率较大肠癌患者高[29．6％（84／284）比14．5％（155／1070）,6．7％（19／284）比0．8％（9／1070）,Wald值分别为25．174和20．496,P值均为0．0011;乙型肝炎表面抗体（抗HBsAb）阳性率较大肠癌患者低『45．4％（129／284）比58．0％（621／1070）,waid=11．062,P=0．0011;HBsAg、HBeAg及乙型肝炎核心抗体（抗HBcAb）同时阳性和HBsAg、乙型肝炎e抗体（抗HBeAb）及抗HBcAb同时阳性的发生率较大肠癌患者高『6．0％（17／284）比0．8％（9／1070）,16-2％（46／284）比11．5％（123／1070）,x0值分别为31．619和4．542,P值分别为0．000和0．033];抗HBcAb阳性且抗HBsAb阴性的发生率也较大肠癌患者高[37．0％（105／284）比24．5％（262／1070）,Wald=17．708,P〈0．001];抗HBcAb和抗HBsAb同时阳性的发生率较大肠癌患者低『20．8％（59／284）比27．8％（297／1070）,Wald=5．646,P=0．017]。结论HBV感染和B细胞型NHL存在一定相关性,HBV感染可能在B细胞型NHL的病原学中起作用。     

原发性肝癌与乙型肝炎病毒感染血清学标记的关系

为了探讨原发性肝癌（PHC）患者血清乙型肝炎病毒（HBV）感染标志在各年龄组间的差异，采用酶联免疫法（ELISA）检测了221例住院病人的血清HBV五项标志。结果发现HBV感染率在各年龄组均呈高值，证实了HBV感染是PHC的一个重要致病因素，尤其是e抗原系统；PHC患者HBeAg阳性率其年龄分布，30岁以后随年龄增长而下降60岁以后明显下降，差异均有显著性（P＜0．05）。30岁～40岁年龄组PHC与60岁后PHC抗-HBe阳性率差异有非常显著性（P＜0．01）。应重视30～40岁年龄组HBV感染的防治。     

粒细胞相关抗原(CD15)在胃癌及癌旁组织中的表达研究

粒细胞相关抗原（CD15）又称LIUM1，主要存在于何杰金病的R-S细胞中[1-6]。我们利用CD15抗体检测了65例胃癌及癌务组织，发现CD15的阳性表达与胃癌的分化程度、组织学类型有显著的相关性；65例胃癌的阳性表达率为66．15％（43／65）．癌旁异形增生腺体的阳性表达率为54．76％（23／42）；正常胃小凹粘膜表达阴性，前二者与后者间有显著的差异性。（P＜0．05）65例胃癌的阳性表达率以管状腺癌（高分化与中分化）为最高（88．46％），低分化腺癌次之（61．11％），以粘液腺癌又次之50％，以卵或细胞癌最低（36．36％）     

定量分析乳腺癌术后化疗前外周血多药耐药基因及其临床意义的研究

目的探讨乳腺癌肿瘤组织多药耐药基因产物P170与外周血多药耐药基因MDR1mRNA的表达及乳腺癌组织ER、PR、癌基因、Her-2之间的相关性及其临床意义。方法应用荧光定量RT-PCR及免疫组化法对32例乳腺癌组织标本P170蛋白表达阳性的病人（试验组）和11例乳腺癌组织标本P170蛋白表达阴性的病人（对照组）进行化疗前的外周血液MDR1mRNA及ER、PR、Her-2检测。结果乳腺癌组织中多药耐药基因产物P170表达阳性的病人中，外周血MDR1mRNA表达阳性者14例（43．75％），阴性18例（56．25％）；乳腺癌组织中多药耐药基因产物P170表达阴性的11例病人中，外周血MDR1mRNA表达阳性者6例（54．55％），阴性5例（45．45％）；P170阳性组外周血MDR1mRNA阳性表达率43．75％与P170阴性组外周血MDR1mRNA阳性表达率54．55％之间差异无相关性（Χ^2=0．383，P〉0．05）。P170阳性组Her-2阳性表达12例（37．50％），阴性20例（62．50％）；P170阴性组Her-2阳性表达2例（18．18％），阴性9例（81．82％）；P170阳性组Her-2阳性表达率37．50％与P170阴性组Her-2阳性表达率18．18％之间差异无显著性（Χ^2=1．391，P〉0．05）。P170阳性组ER表达阳性者13例（40．63％），阴性19例（59．37％）；P170阴性组ER阳性表达者7例（63．64％），阴性4例（36．36％）；P170阳性组ER阳性表达率40．63％与P170阴性组ER阳性表达率63．64％之间差异无相关性（Χ^2=1．742，P〉0．05）。P170阳性组PR阳性表达者20例（62．50％），阴性12例（37．50％）；P170阴性组PR阳性表达者4例（36．36％），阴性7例（63．64％）；P170阳性组PR阳性表达率62．50％与P170阴性组PR阳性表达36．36％之间差异无相关性（Χ^2=2．267，P〉0．05）。P170阳性组淋巴结转移者9例（28．12％），无淋巴结转移23例（71．88％）；P170阴性组淋巴结转移者5例（45．45％），无淋巴结转移6?     

HBVDNA阳性肝癌患者血清HBeAg检测与肝细胞癌复发转移的关系

目的：研究HBVDNA阳性肝癌（HCC）患者血清HBeAg检测与肝细胞癌复发转移的关系。方法：HBVDNA阳性HCC肝切除术患者60例,HBVDNA阴性HCC肝切除术患者60例。60例HBVDNA阳性HCC患者中依据肿瘤病灶局限、肉眼以及镜下均无肝内播散和门静脉浸润的低侵袭组,共28例;肿瘤组织伴有多发性肝内播散和（或）门静脉主肝癌栓者为高侵袭组,共32例。检测患者术前及术后1周血清HBVDNA水平,观察肝功能变化并检测血清HBeAg水平。结果：HBVDNA阳性组与HBVDNA阴性组比较,60例HBVDNA阳性HCC患者中HBeAg阳性患者为48例,阳性率为80％,60例HBVDNA阴性HCC患者中HBeAg阳性患者为12例,阳性率为20％,（P〈0．05）。不同侵袭组HBeAg表达比较：32例高侵袭组中29例HBeAg检测阳性,阳性率为90．62％,28例低侵袭组中19例HBeAg检测阳性,阳性率为67．86％,（P〈0．05）。结论：早期肝癌患者血清HBVDNA和HBeAg可作为肝细胞癌复发转移监测指标。     

肝癌高发区抗-HBc阳性慢性乙肝患者HBVDNA血清学分析

目的：了解启东肝癌高发区抗－HBc阳性慢性乙肝患者HDVDNA分布 情况。方法：采用ELISA法筛选慢性乙肝患者中抗－HBc阳性者，再用聚合酶链反应（PCR）检测这些血清中的HBVDNA。结果：HBVDNA总检出率为75．24％（158／210）。抗－HBc与HBsAg、HBeAg同在时HBVDNA阳性率最高，达97．26％（71／73），显著高于其它模式（P＜0．005）。抗－HBc/HBsAg阳性血清中HBVDNA检出率为81．08％（150／185），单纯抗HBc/HBsAg阳性血清中HBVDNA检出率为80．77％（42／52），单纯抗－HBc阳性血清中检出率为20％（1／5）。结论：抗－HBc是乙肝病毒感染的一个直接标志。判断患者的传染性应通过免疫学和基因学两种方法来检测。启东慢性乙肝患者中HBVDNA整合现象可能要高于其它地区，这或许是启东肝癌高发的机制之一，值得进一步研究。基因学和免疫学方法检测乙肝病毒感染情况各有利弊，应互补共存。     

S100A4、VEGF的表达与胰腺癌预后的关系

目的：研究钙离子结合蛋白S100A4和血管内皮生长因子（vascular endothelial growth factor，VEGF）在胰腺癌组织中的表达，探讨它们的表达与胰腺癌临床病理因素及其与胰腺癌预后的关系。方法：运用免疫组织化学SP法检测62例手术切除的原发性胰腺癌组织中S100A4、VEGF蛋白的表达，比较S100A4、VEGF蛋白表达与临床病理因素的关系及对胰腺癌预后的影响。结果：62例标本中S100A4阳性表达38例（61．3％），VEGF阳性表达37例（59．7％），S100A4、VEGF的表达与胰腺癌显著相关（P〈0．001）。S100A4表达与肿瘤大小、TNM分期及不良预后也显著相关，VEGF与胰腺癌不良预后显著相关。17例S100A4阴性／VEGF阴性胰腺癌患者的预后明显好于其他患者（P〈0．05）。远处转移（P=0．048）、S100A4的阳性表达（P=0．011）和VEGF的阳性表达（P=0．011）是胰腺癌预后的独立影响因素。结论：S100A4和VEGF的高表达在胰腺癌的生长浸润过程中发挥重要作用。对两者的联合检测可更加有效地评估胰腺癌患者的预后。     

EB病毒IgG-EA抗体测定在鼻咽癌筛查中的意义

目的：探讨EB病毒早期抗原（EA）IgG抗体测定在鼻咽癌筛查中的价值。材料和方法：依序列测定方法,用免疫酶染色法对从6257份血清筛查后获得的,IgA／VCA滴度≥1：80的158例血清再进行EBVIgG／EA酶联免疫吸附法（ELISA）测定和IgA／EA抗体免疫酶染色法测定。同时对上述158例血清阳性者进行鼻咽光纤镜和病理检查。根据检查结果比较单项阳性与双项检查阳性血清间鼻咽癌的检出率（阳性预示值）。结果：在这158例阳性血清者中检出鼻咽癌12例。三组阳性血清诊断鼻咽癌的预示值分别是,第一组（IgA／VCA≥1：80）为7．6％（12／158）,第2组（IgA／VCZ≥1：80＋IgA／EA≥1：5）为18．2％（8／44）,第3组（lgA／VCA≥1：8和lgG／EAOD值≥0．18）为15．9％（11／69）。第一组的阳性预示值最低（P＜0．05）,其余两组间无差异P＞005）。第3组检出的11例鼻咽癌包括了第2组中所有的8例鼻咽癌和另外3例IgA／EA阴性鼻咽癌。结论：从序列测定获得的双项阳性血清中筛查到的鼻咽癌比率高于单项lgA／VCA阳性血清。用IgG／EA与IgA／VCA组合测定的双项阳性血清比用IgA／EA与IgA／VCA组合测定的双项阳性血清能查出更多的鼻咽癌,因此该组合更适合于鼻咽癌筛查。     

肝癌患者血清GGT免疫测定法的建立及其在肝癌诊断中的应用

研究建立了肝癌特异GGT免疫测定法。结果阳性OD值≥0．267（—2S）；阴性OD值≤0．065（x＋2S）；肝癌病人血清OD值比正常人高4～11倍。批内及批间CV分别为4．85％和6．27％。初步应用结果显示，对原发性肝癌（PHC）诊断阳性率为86．79％；特异性为94．72％；对继发性肝癌（MHC）诊断阳性率为42．86％；早期诊断阳性率为57．14％。     

Hepatitis B virus e antigen and primary hepatocellular carcinoma.

Serum samples from 243 cases of primary hepatocellular carcinoma (PHC) and 302 non-PHC hospital controls were tested for hepatitis B virus (HBV) surface antigen (HBsAg), antibody to HBsAg (anti-HBs), antibody to HBV core antigen (anti-HBc), HBV e antigen (HBeAg) and antibody to HBeAg (anti-HBe) with radioimmunoassays using commercial kits. A total of 236 (97%) PHC cases and 302 (100%) hospital controls were positive for one or more HBV markers. While 188 (77%) PHC cases and 57 (19%) controls were positive for HBsAg, 44 (18%) PHC cases and 5 (2%) controls were positive for both BHsAg and HBeAg. Statistically significant associations with PHC were observed for HBsAg and HBeAg with an odds ratio (OR) of 10.0 and 3.2, respectively, when age, sex and other markers were adjusted. The stratification analysis of interactive effects of HBV infection markers on the development of PHC showed that HBeAg carrier status may increase PHC risk associated with HBsAg status.     

乙型肝炎病毒感染与原发性肝癌的关联性及危险因素分析

目的 研究乙型肝炎病毒感染与原发性肝癌间关联性,并对危险因素探讨.方法 慢性乙型肝炎病毒感染患者220例,其中慢性乙肝小三阳64例(小三阳组),慢性乙型肝炎大三阳62例(大三阳组),慢性乙型肝炎肝硬化50例(肝硬化组),乙型肝炎相关原发性肝癌44例(原发性肝癌组).观察4组乙肝病毒DNA不同含量(采用乙型肝炎病毒检测试剂盒检测)患者分布情况及表达水平;采用PCR扩增方法 检测4组患者乙肝病毒DNA含量,采用双抗体夹心酶联免疫吸附试验测定乙肝表面抗原.结果 4组患者乙肝病毒DNA不同含量患者分布比较差异有统计学意义(P<0.05),小三阳组DNA不同含量患者分布与大三阳组、肝硬化组、原发性肝癌组比较,差异有统计学意义(P<0.05).小三阳组乙肝病毒DNA表达水平高于大三阳组、肝硬化组和原发性肝癌组,差异有统计学意义(P<0.05),大三阳组乙肝病毒DNA表达水平高于肝硬化组,差异有统计学意义(q=3.884,P<0.05).4组患者乙肝表面抗原水平差异有统计学意义(P<0.05),小三阳组与大三阳、肝硬化组和原发性肝癌组比较,差异有统计学意义(P<0.05),大三阳组与肝硬化组和原发性肝癌组比较,差异有统计学意义(P<0.05).原发性肝癌组5～15年、>15年吸烟率,>15年饮酒率高于肝硬化组,不良饮食、e抗原阳性发生率高于肝硬化组,差异有统计学意义(P<0.05).结论 慢性乙肝小三阳、大三阳、肝硬化、原发性肝癌中,乙型肝炎病毒DNA水平和乙肝表面抗原呈下降趋势,长期吸烟、饮酒,不良饮食习惯和e抗原阳性是原发性肝癌发病的危险因素.     

Hepatitis B viral markers in patients with primary hepatocellular carcinoma in Taiwan

The presence of hepatitis B viral markers in patients with primary hepatocellular carcinoma (PHC) was studied retrospectively at the Taiwan Veterans General Hospital in Taipei, Taiwan. Serum samples from 102 PHC patients and from 100 control individuals were tested for hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs), antibody to hepatitis B core antigen (anti-HBc), hepatitis Be antigen (HBeAg), and antibody to HBeAg (anti-HBe). Of the 102 PHC patients, 72 (71%) were positive for HBsAg. Nine (9%) additional patients were positive for anti-HBc alone in high titer, 19 (19%) had both anti-HBc and anti-HBs, and 9 (9%) had HBsAg, anti-HBc, and anti-HBs. In the 100 controls, 12 (12%) were HBsAg-positive, whereas 22 (22%) had anti-HBc alone and 50 (50%) had both anti-HBc and anti-HBs. Only 4 (4%) controls and no PHC patients had anti-HBs alone. Of the HBsAg-positive patients with PHC, 17 (29%) had HBeAg and 36 (61%) had anti-HBe. The alpha-fetoprotein (AFP) levels above 400 ng/ml were found in 44% of the PHC patients. Values of AFP above 1 x 10(5) ng/ml were more frequently detected in PHC patients who were HBsAg-positive. Categorization of the geographic origins of the families whose members had PHC revealed that most families had originated from southern China. This study confirms that hepatitis B viral markers are frequently present in Chinese patients with PHC.     

Hepatitis B virus infection and primary hepatocellular carcinoma.

Ninety-three patients with biopsy-proven primary hepatocellular carcinoma (PHC) from Uganda, Zambia, and the United States were examined for serologic evidence of hepatitis B virus (HBV) infection. Patients were tested for hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs), antibody to the hepatitis B core antigen (anti-HBc), hepatitis B e antigen (HBeAg), and its antibody (anti-HBe). Active HBV infection, as indicated by positive tests for HBsAg (with or without anti-HBs) and anti-HBc (without anti-HBs), was present in 62% of PHC patients (58 of 93), in contrast with 10% of African controls (9 of 90), and less than 1% of most United States adult populations reported in the literature. The presence of HBeAg or anti-HBe was rare among PHC patients and controls.     

Evidence for clustering of hepatitis B virus infection in families of patients with primary hepatocellular carcinoma.

Family member of 13 patients with hepatitis B surface antigen (HBsAg) positive primary hepatocellular carcinoma (PHC) were tested for the presence of hepatitis B virus-associated antigens and antibodies. Of the 122 members examined, circulating HGsAg was detected in 47 (39%), antibody to HBsAg (anti-HBs) was found in 37 (30%), and antibody to hepatitis B core antigen (anti-HBc) alone was present in 13 (11%). The relatives with the highest frequency of HBsAg positivity were the offspring of the propositus, followed by the nieces and nephews and the grandchildren. Anti-HBs and anti-HBc were detected most often in the spouses and non-blood relatives. Evidence for past and present hepatitis B virus (HBV) infection was more frequently found in the Asian family members when compared to the non-Asians. The e antigen (HBeAg) was present in 38% of the HBsAg positive individuals, including four with PHC; antibody to HBcAg (anti-HBe) was rarely detected. These results indicate that clustering of HBV infection was commonly present in family members of patients with PHC. The HBsAg positive individuals may be major contributors to the endemic pool of the virus, and may themselves be potential cases of chronic active type B hepatitis, cirrhosis, and PHC.     

A case-control study of primary hepatocellular carcinoma in Taiwan

A case-control study was carried out to explore possible risk factors of primary hepatocellular carcinoma (PHC) in Taiwan. One hundred thirty-one PHC patients and 207 hospital control patients were interviewed and blood samples were collected for blood type and hepatitis B virus (HBV) infection marker tests. Eighty-three percent of the PHC patients were found to be hepatitis B surface antigen (HBsAg) positive as compared with 21.0% of the control patients with an odds ratio (OR) of 21.5. Hepatitis B e antigen (HBeAg) positive status increased the risk of PHC. No significant association was observed between erythrocyte genetic markers and PHC, except c of the Rh system, which was significantly lower in the PHC cases. As compared with the control patients, the PHC patients had a higher proportion with a history of liver diseases and more siblings affected with liver diseases. However, the variables such as cigarette smoking, alcohol drinking, peanut consumption, frequent intake of raw fish, heart diseases, peptic ulcer, malaria, hypertension, diabetes, color blindness, G-6-PD deficiency, surgical operation, blood transfusion, and liver diseases of parents and children were not found to be associated with PHC.     

Hepatitis B virus and cigarette smoking: risk factors for hepatocellular carcinoma in Hong Kong

One hundred seven Chinese patients with primary hepatocellular carcinoma (PHC) were compared with 107 hospital controls for the presence of hepatitis B surface antigen and smoking, drinking, and dietary habits. Eighty-two % of PHC cases were hepatitis B surface antigen positive compared to 18% of controls (relative risk, 21.3; 95% confidence limits, 10.1 and 45.9). Prior history of jaundice was significantly related to PHC, independent of hepatitis B surface antigen status. There was a significant association between cigarette smoking and PHC negative for hepatitis B surface antigen. The relative risk of hepatitis B surface antigen-negative PHC for heavy smokers (20 + cigarettes/day) was 3.3 compared to light smokers and nonsmokers (95% confidence limits, 1.0 and 13.4). Our data indicated that infection by the hepatitis B virus and cigarette smoking were independent risk factors for PHC.     

乙肝病毒和黄曲霉毒素与肝癌发生的关系

目的 探讨乙型肝炎病毒（ＨＢＶ）和黄曲霉素素（ＡＦ）与肝癌发生的关系。方法 对５６２例ＨＢｓＡｇ阳性的肝癌高危人群和７１９例ＨＢｓＡｇ阴性的对照人群进行１０年前瞻观察,同时采用抗ＡＦＭ１高亲和力的单克隆抗体系统,以免疫浓和高压液相（ＨＰＬＣ）系列测定由２５例肝癌和１２５例非肝癌对象组成的病例对照人（１：５）尿中ＡＦＭ１排出量。结果 （１）ＨＢｓＡｇｂｊ ｎｔｇ ｘｅｇ ｅｆｈ ｕｋｋｍｗ ｒｈ ｆ     

青少年原发性肝癌与乙型和丙型肝炎病毒感染的相关性分析

目的探讨青少年原发性肝癌(PHC)患者中乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)及HBV和HCV混合感染率及其相互关系。方法将50例青少年PHC患者纳入观察组,将同期住院的50例其他肝病患者纳入对照组,检测两组患者血清中HBV、HCV、HBV/HCV标志物阳性率等情况。结果观察组患者血清中HBsAg、抗Hbe和HBV-DNA阳性率均显著高于对照组患者,差异有统计学意义(P<0.05)。两组患者血清中HBeAg阳性率比较,差异无统计学意义(P>0.05)。观察组和对照组患者血清中抗HCV和HCV-RNA阳性率比较,差异无统计学意义(P>0.05);HBV(+)HCV(+)和HBV(+)HCV(-)与青少年PHC发病呈正相关性(P<0.05),HBV(-)HCV(+)与青少年PHC发病无相关性(P>0.05),HBV(-)HCV(-)与青少年PHC发病呈负相关性(P<0.05)。结论 HBV感染与青少年PHC发病有着较强的相关性,属高度危险因素。     

异基因造血干细胞移植中供受体乙肝病毒感染的意义

 目的 分析白血病患者移植前供、受者感染乙型肝炎病毒（HBV）对异基因造血干细胞移植（allo-HSCT）临床结果的影响。方法 对该院1996年5月至2005年2月间进行的31例合并HBV感染的HSCT患者临床资料进行回顾性分析。结果 31例受者均达到造血干细胞植活,乙型肝炎指标供者阳性、受者阴性8例,其中1例26个月死于肝硬化,2例在免疫抑制剂停用后,发展为慢性活动性肝炎;乙型肝炎指标供者阴性、受者阳性20例,其中2例乙型肝炎指标转阴,5例获得HBsAb（+）,4例移植后HBcAb转阴及HBeAb转阴,仅HBsAb（+）,1例转为"HBsAg（+）、HBeAg（+）、HBcAb（+）";乙型肝炎指标供者、受者均阳性3例,1例患者并发肝静脉闭塞病（VOD）,1例获得一过性HbsAg（+）,1例获得HbsAb（+）。结论 HBV感染对干细胞植活时间无明显影响;供、受者感染乙肝病毒不是HSCT的绝对禁忌证;HBsAg（+）及HBV滴度是影响移植后乙型肝炎复发的重要因素;HBsAg（+）的患者可作为HbsAb（+）受者的供者,但对HbsAb（-）受者则应慎重;拉米夫定及乙肝免疫球蛋白联合应用较乙肝疫苗单独使用更能有效地控制HBsAg（+）的供受者在移植后的乙型肝炎疾病的进展;HSCT有可能通过过继免疫治疗乙型肝炎。