中国人群HBV和HCV双重感染与肝细胞癌关系的Meta分析

目的：综合评价中国人群中乙型肝炎病毒（hepatitis B virus，HBV）、丙型肝炎病毒（hepatitis C virus，HCV）双重感染者发生肝细胞癌（hepatocellular carcinoma，HCC）的危险是否高于单独感染者。方法：检索中国生物医学数据库和Medline，获得1990～2006发表的有关中国人群HBV和HCV双重感染与HCC关系的研究结果，并进行Meta分析。所有文献均为病例对照研究。采用随机效应模型D-L法计算合并0R值及其95％CI。结果：共检索到符合要求的37篇文献，累计病例、对照数分别为4203和5642例。与未感染者相比，HBV、HCV单独感染发生HCC的合并优势比（OR）分别为20．91（95％CI：15．40～28．40）和10．60（95％CI：6．74～16．65）；HBV、HCV双重感染发生HCC的合并优势比（OR）为50．27（95％CI：34．92～72．38）。结论：HBV、HCV感染是中国人群HCC高发的独立危险因素，HBV和HCV双重感染在HCC发生过程中呈协同作用。     

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。     

乙肝病毒前S1抗原检测在乙型肝炎向肝癌演变中的临床意义

目的探讨前S1抗原与原发性肝癌（PHC）的关系。方法采用ELISA法检测302例PHC患者的血清学乙肝病毒标志物（HBVM）及前S1抗原。结果302例PHC患者，HBVM检出率为99．0％（299／302）。其中单项阳性率HBsAg94．0％（284／302）、AntiHBs5．6％（17／302）、HBeAg20．2％（61／302）、AntiHBe72．8％（220／302）、AntiHBc97．4％（294／302）。61例HBeAg阳性样本中前S1抗原阳性46例（75．4％）；而196例HBeAg阴性AntiHBe阳性标本中前S1抗原阳性98例（50．0％）；而35例HBeAg和AntiHBe均阴性标本中前S1抗原阳性10例（26．3％）。前S1抗原在血清学表达上与HBeAg的阳性符合率高达75．4％。结论血清前S1抗原是乙型肝炎病毒（HBV）在体内复制的可靠标志，通过检测血清前S1抗原有助于提高认识PHC发生的可能性。     

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。     

HCC病理学和超微结构与HBV、HCV感染关系的研究

目的 探讨肝细胞癌（Hepatocellular carcinoma,HCC)组织学类型与分化度的关系，以及与乙肝病毒（HBV），丙肝病毒（HCV）感染的关系。方法 70例手术切除的HCC组织，常规制备石蜡切片和超薄切片，并检测血清中HBVM及Anti-HCV。结果 光镜下HCC的梁索型，电镜下癌细胞核为大而圆，染色质疏松，核膜薄，溶酶体和自噬体增多，线粒体增多；光镜下HCC的透明细胞型，电镜下核小，胞浆疏松化，细胞器减少，线粒体空泡变，粗面内质网脱核糖体。肝细胞癌中HBV感染61例，阳性率为87．14％，抗HCV阳性11例，阳性率为15．71％，二者重叠感染4 ，阳性率为5．71％。结论 梁索型HCC的分裂能力强，透明细胞型HCC易发生破裂和溶解。HCC与HBV，HCV感染密切相关，HBV是HCC发生的主要病因。     

原发性肝癌患者HBV感染血清学模式调查

目的：研究HBV感染血清学模式与原发性肝癌的关系。方法：分析1996年6月－2000年9月我院收治的500例原发性肝癌患者的HBV感染血清学模式，与同期收治的500例其他恶性肿瘤患者的HBV感染血清学模式进行比较，结果：原发性肝癌患者HBV感染率为89．6％，显著高于其他恶性肿瘤患者，HBsAg和HBcAb同时阳性者占HBV感染肝癌的79．9％，占HBV感染其他恶性肿瘤的13．3％，差异有极显著性（P＜0．01），出现HBsAb者占原发性肝癌中HBV感染病例的8．5％，其他恶性肿瘤中HBV感染病例的75．1％，两者差异亦有极显著性（P＜0．01），大三阳，小三阳和（HBsAg HBcAb )者与肝癌相关的OR分别为13．85，6．95和14．69。结论：HBsAg和HBcAb同时阳性的患者患肝癌的危险性最高；血清出现HBsAb的HBV感染者不易发展成肝癌。     

Epstein—Barr病毒在肝细胞癌发生中的作用探讨

目的：了解肝细胞癌(hepatocellular carcinoma，HCC)患者的EpsteinBarr病毒(EBV)感染情况，探讨EBV与肝炎病毒有无协同致癌作用。方法：研究组为78例HCC石蜡标本，对照组为26例非癌症肝组织标本。用PCR检测EBV，DNA(BarnHl W，LMP1)、HBV DNA(S基因、X基因)，用RT—PCR检测HCV RNA和HDV RNA，用免疫组化检测EBV(LMP1)、HBV(HBsAg、HbcAg)和HCV。结果：EBV DNA在HCC组阳性率高于对照组(28．2％vs8．0％)，X^2=4．622，P=0．032；HBV DNA在HCC组阳性率高于对照组(56．4％vs23．1％)，X^2=8．681，P=0．008；EBV与HBV在HCC组无相关关系，X^2=0．835，P=0．375。HCV RNA、HDV RNA在18例HCC中阳性分别为1和0例。免疫细化测EBV在HCC组阳性率高于对照细(32．1％vs2．5％)，X^2=6．02，P=0．012；HBV在HCC组阳性率高于对照细(57．7％vs5．1％)，X^2=10．03。P=0．001。结论：EBV在HCC发生中可能起作用，与HBV无明显协同致癌作用;HCV、HDV检出率不高，与EBV关系未能确定。     

淋巴细胞恶性增生性疾病患者肝炎病毒感染状况的分析

目的研究淋巴细胞恶性增生性疾病（MLPD）患者乙型（HBV）、丙型（HCV）肝炎病毒感染情况.方法回顾性分析67例初诊MLPD和170例正常体检人群血清乙型肝炎病毒标记物和抗HCV.结果 67例MLPD中HBV阳性10例（14 93%）.其中33例淋巴瘤（NHL/HD）中6例阳性,16例MM中2例阳性,18例淋巴细胞白血病（ALL/CLL）中2例阳性,170例体检人员中8例阳性（4.71%）,MLPD患者群体内HBV感染的阳性率高于正常人群的HBV感染的阳性率（P＜0.01）;67例MLpD中抗HCV阳性5例（7.46%）,其中33例淋巴瘤中2例阳性,16例MM中2例阳性,18例淋巴细胞白血病中1例阳性,170例体检人员中2例阳性（1.18%）.MLPD患者群体内抗HCV的阳性率高于正常人群抗HCV的阳性率（P＜0.05）.结论 MLPD患者有较高的HBV和HCV感染率.     

肝癌患者HBV、HCV、HGV、TTV感染状况及其介入治疗中术者感染的预防

目的 通过了解肝癌患HBV、HCV、HGV、TTV感染状况，探讨在肝癌介入治疗术中经血源传播病原体感染的可能性及预防。方法 采用免疫PCR检测HBVDNA、套式PCR检测HCV、RNA、HGV RNA、TTV DNA。结果 30例肝癌患血清中单纯HBV DNA阳性率（16/30）53.3%、HCV RNA阳性率（4/30）13.3%；二重感染HBV DNA、HCV RNA阳性率（2/30）6.7%、HBV DNA、HGVRNA阳性率（1/30）3.3%、HBVDNA、TTVDNA阳性率（10/30）33.3% ;HCVRNA、TTVDNA阳性率（1/30）3.3%,HCVRNA、HGVRNA阳性率（10/30）3.3%，HCVRNA、TTVDNA阳性率（1/30）3.3%、HCVRNA、HGVRNA阳性率（1/30）3.3%；三重感染HBVDNA、HCVRNA、HCVRNA、HGVRNA阳性率（1/30）3.3%。结论 肝癌与肝炎病毒的感染有关，且存在较高比率的重叠感染。介入治疗中存在被感染的可能性。其预防十分重要。     

原发性肝癌与其他恶性肿瘤患者HBV及HCV感染率调查

目的：研究原发性肝癌与其他恶性肿瘤患者HBV及HCV感染率，方法：对156例原发性肝癌患者，786例其他恶性肿瘤患者进行乙肝五项指标及抗HCV检测，并与180例健康对照者进行比较。结果：三组资料的HBV感染率分别为80．13％，23．92％和10．56％，差异有显著性；HCV感染率分别为5．13％，3．94％和2．78％，差异无显著性，结论：原发性肝癌与其他恶性肿瘤患者的HBV感染率明显高于健康对照组，HCV感染率与健康对照组相差异无显著性。     

ABO血型与PHC患者HBV感染标记相关性研究

研究伴ＨＢＶ感染的ＰＨＣ４４５例乙型肝炎抗原抗体与ＡＢＯ血型的关系，结果表明：１．伴ＨＢＶ感染的ＰＨＣＡ型血者显著高于对照组（Ｐ＜０．０１）。２．ＰＨＣ患者中ＨＢｓＡｇ、抗－ＨＢｃ的阳性率均以Ａ型血显著高于对照组（Ｐ＜０．０５）。３．ＰＨＣ患者中ＨＢｓＡｇ与抗－ＨＢｃ均阳性模式Ａ型血者显著多于对照组，而Ｂ型血者显著少（Ｐ＜０．０５）；抗－ＨＢｅ与抗ＨＢｃ均阳性的ＰＨＣ中，亦为Ａ型血者显著多（Ｐ＜０．０５）。提示有ＨＢＶ感染的Ａ型血者罹患ＰＨＣ的倾向性最高；而有ＨＢＶＭ、ＨＢｓＡｇ、抗－ＨＢｃ的Ａ型血者则为ＰＨＣ的易感人群，其中以ＨＢｓＡｇ和抗－ＨＢｃ同时阳性或抗－ＨＢｅ和抗－ＨＢｃ同时阳性的感染模式更易发生ＰＨＣ；也提示ＰＨＣ、ＨＢＶ、Ａ型血三者之间存在某种密切的、复杂的联系，对ＰＨＣ的发生有协同作用。对上述人群应密切关注，定期复查，以期早诊早治。     

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.     

Case-control study on hepatitis C virus (HCV) as a risk factor for hepatocellular carcinoma: the role of HCV genotypes and the synergism with hepatitis B virus and alcohol. Brescia HCC Study.

We performed a case-control study to evaluate the risk of hepatocellular carcinoma (HCC) for hepatitis C virus (HCV) infection. A total of 305 newly diagnosed HCC cases (80% males) and 610 subjects (81% males) unaffected by clinically evident hepatic disease admitted to the 2 main hospitals in Brescia, North Italy, were recruited as cases and controls, respectively. Among the 122 HCC cases positive for HCV RNA, genotype 1b was found in 83 patients (68%), genotype 2 in 36 (29.5%) and genotype 1a in 3 (2.5%). Among the controls, 15 were infected with genotype 1b and 15 with type 2. Analysis of HCV envelope 1 nucleotide sequence among 25 cases and 8 controls infected with genotype 2 showed subtype 2c in 96% of cases and in all controls, and subtype 2a in 1 HCC case. The odds ratio (OR) for HCV RNA positivity adjusted for hepatitis B virus (HBV) markers and alcohol intake was 26.3 [95% confidence interval (CI): 15.8-44], and it was higher for genotype 1b (OR = 34.2) than type 2 (OR = 14.4). The OR for HCV RNA was 35.6 (95% CI: 14.5-87.1) when the HBV markers were all negative and 132 (15.3-890) when HBsAg positivity was present; the OR was 26.1 (95% CI: 12.6-54.0) among subjects with alcohol intake of 0-40 g/day and increased to 62.6 (23.3-168) and 126 (42.8-373) with an alcohol intake of 41-80 and >80 g/day, respectively. In conclusion, synergism was found between HCV infection and HBV infection and alcohol intake in causing HCC.     

A meta-analysis of epidemiological studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma

The aim of the study was to assess whether co-infection by hepatitis-B virus (HBV) and hepatitis-C virus (HCV) is associated with a higher risk of developing hepatocellular carcinoma (HCC) than each infection alone. A meta-analysis of data published up to June 1997 was performed. HBsAg and anti-HCV antibodies or HCV RNA (anti-HCV/HCV RNA) were considered as serological markers of current HBV and HCV infection respectively. A total of 32 case-control studies were suitable for a quantitative overview. The summary odds ratios (OR) were 13.7 for HBsAg positivity and 11.5 for anti-HCV/HCV RNA positivity. The OR for anti-HCV was lower among studies using second- or third-generation anti-HCV or HCV RNA (OR, 8.2) with respect to studies with first-generation anti-HCV test (OR, 19.1). When combining data from the studies with second- or third-generation anti-HCV or HCV RNA, the OR for HBsAg positivity and anti-HCV/HCV RNA negativity was 22.5 (95% confidence interval (CI), 19.5–26.0), the OR for anti-HCV/HCV RNA positivity and HBsAg negativity was 17.3 (95% CI, 13.9–21.6), and the OR for both markers positivity was 165 (95% CI: 81.2–374, based on 191 cases and 8 controls exposed). A synergism was found between HBV and HCV infections, the OR for co-infection being greater than the sum and lower than the product of those for each infection alone. The interaction was therefore negative according to the multiplicative model, providing epidemiological evidence both of an independent effect and of interference between the 2 viruses in the carcinogenic process. Int. J. Cancer 75:347–354, 1998. © 1998 Wiley-Liss, Inc.     

肝癌患者同胞罹患原发性肝癌的因素及特征

本文对１５２例具有同胞患肝癌家族史的原发性肝癌先证者进行分析，结果表明：该组人群ＨＢＶ感染率为８１．５８％，感染标记类型有１２种，其中６８％为抗一ＨＢｃ阳性伴ＨＢｓＡｇ和（或）抗－ＨＢｅ阳性；发病高峰年龄为３０～４９岁（占７２％）；兄弟同患肝癌（６７．１１％）显著多于兄妹、姐弟同患，更显著多于姐妹同患（Ｐ＜０．００１），但伴有母患肝癌家族史的患者女性同胞也易患肝癌（Ｐ＜０．０２５）。提示具有同胞患肝癌史、年龄３０～４９岁、尤其是抗－ＨＢｃ阳性伴ＨＢｓＡｇ和（或）抗－ＨＢｅ阳性的男性乙肝患者为肝癌患者一级亲属中原发性肝癌最易感人群，应密切关注，警惕肝癌发生。     

肝癌患者一级亲属HBV感染的调查分析

本文从ＨＢＶ感染的角度研究肝癌家族内的遗传效应。结果表明：１，原发性肝癌（ＰＨＣ）患者一级亲属２２７人。其乙型肝炎病毒感染标记（ＨＢＶＭ）阳性率为７１．８１％，ＨＢｓＡｇ阳性率为４２．７３％，显著高于当地的自然人群（Ｐ＜０．０５）；其ＨＢＶＭ最常见模式是ＨＢｓＡｇ、抗－ＨＢｅ和抗－ＨＢｃ同时阳性，与有ＨＢＶ感染的ＰＨＣ患者ＨＢＶＭ的最常见模式相一致。２．患者同胞的ＨＢＶＭ阳性率为８２，９８％，ＨＢｓＡｇ为５１．０％，均显著高于患者双亲、子代（Ｐ＜０．０５）；且男性显著多于女性（Ｐ＜０．０５）。３．患者母亲组的ＨＢＶＭ明显高于父亲组（＋３１．４３％）。提示ＰＨＣ患者一级亲属确是一组ＨＢＶ易感人群，且肝癌家族内ＨＢＶ感染、ＰＨＣ都呈明显的、以母系亲代传递为特征的家族聚集现象；ＨＢＶ经垂直感染可导致家族性ＰＨＣ，ＰＨＣ患者同胞（尤其男性）是ＨＢＶ、ＰＨＣ最易感人群。因此，对该人群需密切关注，定期复查，警惕ＰＨＣ的发生。     

原发性肝癌与其他恶性肿瘤患者HBV及HCV感染率调查

目的 :研究原发性肝癌与其他恶性肿瘤患者HBV及HCV感染率。方法 :对 156例原发性肝癌患者、786例其他恶性肿瘤患者进行乙肝五项指标及抗HCV检测 ,并与 180例健康对照者进行比较。结果 :三组资料的HBV感染率分别为 80 .13%、2 3.92 %和 10 .56% ,差异有显著性 ;HCV感染率分别为5.13%、3.94 %和 2 .78% ,差异无显著性。结论 :原发性肝癌与其他恶性肿瘤患者的HBV感染率明显高于健康对照组 ,HCV感染率与健康对照组相比差异无显著性。     

HCV、HBV与肝硬变及原发性肝癌关系的初步探讨

作者对８０例肝硬变（ＬＣ）、１１２例原发性肝癌（ＰＨＣ）的血清抗ＨＣＶ及ＨＢＶ检测发现：（１）ＰＨＣ、ＬＣ的抗ＨＣＶ阳性率分别为２８．６％和１８．８％，ＨＢＶ阳性率分别为６４．３％和６７．５％；（２）有无用血液及血液制品者间的抗ＨＣＶ及ＨＢＶ阳性率差异显著；（３）ＬＣ、ＰＨＣ患者的抗ＨＣＶ阳性率在ＨＢＶ阴性（１５．４％和２５％）与ＨＢＶ阳性（２０．４％和３０．６％）间无明显差异；（４）在抗ＨＣＶ阴、阳性ＰＨｃ中，抗ＨＢｅ、抗ＨＢｃ单阳性率，抗ＨＢｓ与抗ＨＢＣ及抗ＨＢｃ与抗ＨＢｅ双阳性率，差异非常显著。结果表明，ＨＢＶ感染仍为ＬＣ及ＰＨＣ的主要致病因素，但ＨＣＶ与ＨＢＶ存在着重叠感染，亦可能起着共同作用。     

Dietary glycemic load and hepatocellular carcinoma with or without chronic hepatitis infection

BackgroundHepatitis B virus (HBV) and hepatitis C virus (HCV) are the major risk factors for hepatocellular carcinoma (HCC). The association of diabetes mellitus with HCC suggests that dietary glycemic load (GL) may influence HCC risk. We have examined the association between dietary GL and HCC.Patients and methodsWe conducted a hospital-based case–control study in Italy in 1999–2002, including 185 HCC cases and 412 controls who answered a validated food frequency questionnaire and provided blood samples. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were computed using unconditional multiple logistic regression.ResultsWe observed a positive association between GL and HCC overall, with an OR of 3.02 (95% CI 1.49–6.12) for the highest quintile of GL compared with the lowest and a significant trend. The OR among HCC cases with evidence of chronic infection with HBV and/or HCV was 3.25 (95% CI 1.46–7.22), while the OR among those with no evidence of infection was 2.45 (95% CI 0.69–8.64), with no significant trend. The association was not explained by the presence of cirrhosis or diabetes.ConclusionsHigh dietary GL is associated with increased risk for HCC. The positive association was most pronounced among HCC cases with HBV and/or HCV markers.