广州地区424例乙型肝炎患者病毒基因亚型分布与乙型肝炎疾病谱的关系探讨

目的调查广州地区乙型肝炎病毒(HBV)基因亚型分布情况,并探讨其与HBV感染疾病谱的关系。方法采用直接测序法测定S基因序列并构建基于S基因进化树,对424例HBV感染者进行研究,随机选择慢性乙型肝炎(CHB)137例,HBV相关慢加急性肝衰竭(HB-ACLF)90例,肝硬化(LC)90例和肝细胞癌(HCC)107例,应用SPSS 13.0软件进行x~2检验、方差分析和多元Logistic回归分析。结果在424例HBV感染者中,B2亚型269例(63.44%),C1亚型117例(27.59%),C2亚型36例(8.49%),C5亚型2例(0.47%),未发现其他亚型;CHB患者感染HBV B2亚型、C1亚型、C2亚型和C5亚型分别为70.1%、24.09%、5.11%和0.73%;HB-ACLF患者感染HBV B2亚型、C1亚型和C2亚型分别为87.78%、7.78%、4.44%,其中HBV B2基因亚型显著高于CHB(x~2=9.641,P=0.002)、LC(x~2=19.565,P=0.000)、HCC患者(x~2=26.789,P=0.000);LC患者感染HBV B2亚型、C1亚型和C2亚型分别为50.00%、36.67%、13.33%,其中HBV C1和C2亚型显著高于CHB患者(x~2=6.262,P=0.012;x~2=4.790,P=0.029)或HB-ACLF患者(x~2=25.894,P=0.000;x~2=4.390,P=0.036);HCC患者感染HBV B2亚型、C1亚型、C2亚型和C5亚型分别为45.79%、41.12%、12.15%、0.93%,其中HBV C1和C2亚型也显著高于CHB患者(x~2=11.264,P=0.001;x~2=3.957,P=0.047)或HB-ACLF患者(x~2=28.327,P=0.000;x~2=3.904,P=0.048);LC和HCC患者HBV C1和C2基因亚型无明显差异(x~2=0.429,P=0.512;x~2=0.804,P=0.833);多因素Logistic回归分析提示B2亚型是HB-ACLF发生的危险因素(OR=2.597,95%CI=1.145~5.891,P=0.022),C型是HCC发生的危险因素(OR=3.257,95%CI=1.49~7.194,P=0.003)。结论广州地区HBV基因亚型主要由B2、C1和C2亚型构成,同时也存在C5亚型;广州地区B2亚型感染者可能更易发生HBV相关慢加急性肝衰竭,而C1和C2亚型感染者可能更易进展为肝硬化和肝细胞癌。     

慢性乙型肝炎患者HBV基因型分布及其耐药基因突变分析*

目的 探讨慢性乙型肝炎（CHB）患者HBV基因型及其耐药突变发生情况。方法 纳入240例接受核苷（酸）类似物单药或联合或序贯治疗的CHB患者,采用PCR扩增HBV逆转录（RT）区和序列测定鉴定耐药基因突变,采用HBV S基因测序法鉴定基因型。结果 在35例单用拉米夫定治疗的CHB患者中,发生耐药突变14例（40.0%）,突变位点为rtL80I/V、rtVl73L、rtLl80M、rtM204V/I和rtV207I,23例单用阿德福韦治疗者发生耐药突变11例（47.8%）,突变位点为rtAl81T/V、rtS213T/N、rtV214A、rtQ215S/H/P、rtl233V、rtN236T、rtP237H和rtN/H238A/K/D/S,70例单用恩替卡韦治疗者发生耐药突变10例（14.3%）,突变位点为rtM204I,12例单用替比夫定治疗者发生耐药突变5例（41.7%）,突变位点为rtI169T、rtL180M、rtT184G/S/A/I/L/F、rtS202I/G、rtM204V和rtM250V/I/L,100例接受联合或序贯治疗者发生耐药突变51例（51.0%）,突变位点为rtA194T,恩替卡韦治疗患者耐药突变发生率最低（P<0.05）;240例CHB患者中,HBV基因B型21例（8.8%）、C型216例（90.0）和D型3例（1.2%）;在发生耐药突变的91例患者中,B型6例（6.6%）、C型83例（91.2%）和D型2例（2.2%,x²=1.22,P>0.05）;在发生耐药突变的6例B型感染者中有2例（33.3%）和83例C型感染者中有15例（18.1%）发生了多重耐药突变。结论 检测CHB患者感染HBV基因型并及时获得耐药突变基因分布,将有助于指导临床治疗。     

贵州地区慢性乙型肝炎病毒感染者病毒基因亚型研究

目的调查贵州省B、C基因型慢性HBV感染者的病毒基因亚型。方法PCR扩增HBV P区长309 bp的基因片段,扩增产物分别经限制性内切酶NciⅠ、VspⅠ、BstEⅡ酶切,琼脂糖凝胶电泳,根据酶切图谱多态性,用限制性片段长度多态性分析（PCR-RFLP）检测HBV C基因亚型。直接测序确定B基因亚型、对178例用S基因限制性片段长度多态性鉴定为B、C基因型的不同临床类型慢性HBV感染者进行亚型分析。结果84例C基因型HBV感染者中,27例（32.14%）为C1亚型、56例（66.67%）为C2亚型,1例为C1、C2亚型混合感染。94例B基因型HBV感染者中,93例（98.94%）为Ba、1例为Bj亚型感染。从无症状乙型肝炎表面抗原携带者、CHB到肝硬化/肝癌,C1亚型在各组中的比例逐渐降低,分别为60.00%、30.65%和16.67%;而C2亚型在各对应组中的分布逐渐增高,分别为40.00%、67.74%和83.33%。结论贵州地区B、C基因型慢性HBV感染者中,以Ba、C2亚型为主。C1、C2亚型在疾病中的分布有一定差异。PCR-RFLP分析HBV C1、C2亚型,方法简便、特异性强,适合较大样本分析,可用于流行病学调查。     

慢性乙型肝炎的免疫治疗研究进展*

临床上应用的抗乙型肝炎病毒（HBV）药物主要有干扰素和核苷（酸）类似物两类,在大多数慢性HBV感染者即使经过长期的抗病毒治疗仍不能彻底清除病毒。感染的控制和病毒的清除有赖于机体的免疫系统。感染慢性化与机体特异性免疫功能,尤其是细胞免疫功能低下密切相关。通过增强抗HBV感染的免疫治疗是被人们寄予厚望的一种治疗策略。目前研究的热点主要包括免疫激动剂、特异性细胞毒性T淋巴细胞（CTL）负调节分子阻断剂、特异性CTL调节分子激动剂或佐剂、治疗性疫苗、特异性T细胞受体（TCR）转基因技术、携带嵌合抗原受体的T细胞和多糖类物质等,本文对近年来这方面的研究进展进行了综述。     

1例输入性HIV-1 G亚型毒株的检出及基因组序列分析

目的 对1例输入性HIV-l G亚型感染者病毒基因组进行序列测定,并进行系统进化分析.方法 采集在本地区艾滋病监测中发现的1例HIV-1 G亚型感染者的血清,提取病毒RNA,利用反转录巢式-PCR技术扩增并测定病毒近似全长基因序列.结果 获得此毒株近似全长基因组序列,长度为8695 bp.重组分析结果显示,此毒株序列中...     

39例成人急性乙型肝炎患者血清HBV基因变异检测及其临床意义探讨*

目的了解成人急性乙型肝炎患者流行的病毒基因型及基因变异情况。方法在2010年12月~2014年1月北京佑安医院收治39例急性乙型肝炎患者,采用直接基因测序法和平行等位基因特异性检测技术检测HBV基因型、P区、S区、前C区（PreC）和基本核心启动子（BCP） 区序列。结果在39例患者中,成功测序35例。35例急性乙型肝炎患者感染HBV B基因型12例（36.4%）,C基因型21例（57.6%,D基因型2例（6.0%）;通过直接测序法和PASS法均检测到同1例患者存在A181S耐药变异,变异病毒占准种池比例达100%;直接测序法检测到1例患者存在S区S132F和W172C变异;1例患者存在PreC/BCP 区G1896A和T1758C变异。结论急性乙型肝炎患者感染病毒基因型与文献报道的慢性乙型肝炎患者感染病毒基因型分布一致,以C型和B型为主,存在P区、S区和PreC/BCP区变异可能,未见不同病毒株感染引起转归的不同。     

慢性乙型肝炎病毒携带者血清GP73水平与肝组织病理学变化的关系研究*

目的 探讨慢性乙型肝炎病毒携带者血清高尔基体蛋白73（GP73）水平与肝组织病理学变化的关系。方法 2014年1月~2016年12月我院诊治的慢性HBV携带者150例、慢性乙型肝炎患者150例和乙型肝炎肝硬化患者150例,另选同期健康人50例,采用ELISA法检测GP73水平,对150例慢性HBV携带者进行肝穿刺活检,采用Metavir评分对肝组织炎症和纤维化进行评价。结果 慢性HBV携带者血清GP73水平为（46.5±7.8） ng/ml,慢性乙型肝炎组为（90.2±10.9） ng/ml,乙型肝炎肝硬化组为（231.6±20.1） ng/ml,均显著高于健康人组的（36.7±6.6） ng/ml,差异有统计学意义（P<0.05）,肝硬化患者血清GP73水平也显著高于慢性乙型肝炎或HBV携带者（P<0.05）;经肝组织检查,150例慢性HBV携带者肝内炎症活动度分级和纤维化分期表现为G₀~G₁ 105例,G₂ 30例,G₃~G₄ 15例,其血清GP73水平分别为（45.2±12.8）ng/ml、（63.8±15.0）ng/ml和（83.7±20.1）ng/ml,S₀~S₁ 98例,S₂ 3₀例,S₃~S₄ 22例,其血清GP73水平分别为（45.1±16.8）ng/ml、（67.3±16.4）ng/ml和（72.0±18.4）ng/ml,肝组织炎症活动度分级和纤维化分期严重的患者血清GP73水平显著升高,与分级或分期轻的人群比,差异有统计学意义（F=16.8,F=19.2,P均<0.05）;Logistic回归分析发现血清GP73水平升高是慢性HBV携带者肝组织显著炎症（OR=1.1,95 % CI:1.0~1.1,P<0.05）和显著肝纤维化（OR=2.1,95% CI:0.8~1.2,P<0.05）的高危因素。结论 检测血清GP73水平可能有助于对慢性HBV携带者肝组织炎症分级和纤维化分期的判断,能否作为预测慢性HBV携带者肝组织炎症分级和纤维化分期的潜在标志物,还需要扩大验证。     

乙型肝炎病毒感染者病毒基因型和亚型分布及其临床意义

目的研究不同类型乙型肝炎病毒（HBV）感染者中HBV基因型和亚型分布情况及其临床意义。方法应用基因型和亚型特异性引物聚合酶链反应法（PCR），对北京、长春、汉川，深圳，清远和南京等6个城市445份HBV感染者血清进行基因型及亚型分型，其中急性肝炎7例，无症状携带者36例，慢性乙型肝炎352例，肝硬化28例，肝细胞癌22例。通过对PCR产物测序确定其基因型，以验证该法的准确性。结果445份血清中，239例（53．7％）为C型，其中13例（5．4％）为C1亚型，135例（56．5％）为C2亚型，91例（38．1％）为非C1／C2亚型；145例（32．6％）B型，其中100例（69．0％）为Ba亚型，25例（17．2％）为Bj亚型，20例（13．8％）为非Ba／Bj亚型；61例（13．7％）为B型与C型混合感染，其中6例（9．8％）为Ba与C1亚型混合感染，3例（4．9％）为Bj与C1亚型混合感染，15例（24．6％）为Ba与C2亚型混合感染，8例（13．1％）为Bj与C2型混合感染，11例（18．0％）为Ba与非C1／C2亚型混合感染，7例（11．5％）为Bj与非C1／C2亚型混合感染，2例（3．3％）为非Ba／Bj亚型与C1亚型混合感染，3例（4．9％）为非Ba／Bj亚型与C2亚型混合感染，6例（9．8％）为非Ba／BJ亚型与非C1／C2亚型混合感染。未检测到其他基因型及亚型。在不同类型乙型肝炎病毒感染者中，B型，C型、B与C型混合感染及亚型分布差异有统计学意义，在肝硬化和肝细胞癌患者中C型所占比例较高（分别为78．6％和86．4％），无症状携带者中B型所占比例较高（72．2％）。但不同性别患者中，HBV基因型和亚型分布无差异。在HBeAg阳性和阴性感染者中，HBV基因型和亚型分布差异也有统计学意义。结论该6个城市HBV感染者中，以B2和C2亚型占优势，C基因型可能与肝硬化和肝细胞癌的发生有关。     

乙型肝炎病毒导致的肝硬化伴肝癌患者血清中N糖组学改变

肝细胞癌（HCC）是最常见的肿瘤和最主要的死因之一，多发生于HBV和HCV感染导致的肝硬化患者，筛查肝硬化人群，早期诊断HCC可降低肿瘤的病死率。甲胎蛋白（AFP）是目前广泛应用的辅助诊断HCC的血清学指标，是对B超、CT等影像学诊断的有效补充。最近的荟萃分析表明，不同研究论文报道的AFP的灵敏度和特异度有很大的不同，这种现象不能完全用AFP的临界值不同解释。血清中的N糖蛋白主要由肝脏和B淋巴细胞合成，N糖成分的改变可反应肝脏或B淋巴细胞功能的改变，糖链的改变常常反应出机体的异常改变。糖组学在诊断领域的应用曾经因为缺少合适的分析技术而受限制，血清中N糖组学分析技术克服了这一屏障。本研究的目的是评价血清中N糖指纹图谱应用于乙型肝炎后肝硬化伴肝癌辅助诊断的意义。     

乙型肝炎和肝癌患者乙型肝炎病毒前C区1896位点突变的研究

为探索乙型肝炎病毒前Ｃ区突变是否与肝损程度及肝癌发生有关，对１３９例ＨＢｓＡｇ、ＨＢＶＤＮＡ和抗－ＨＢｅ阳性，ＨＢｅＡｇ阴性的慢性ＨＢＶ感染者和肝癌患者的血清标本，采用３＇碱基特异性聚合酶反应进行了第１８９６位核苷酸突变的检测分析。     

厦门市乙型肝炎病毒亚基因型分布的初步研究

目的探讨厦门地区乙型肝炎患者血清乙型肝炎病毒（HBV）基因型的分布情况。方法应用混合性型特异性引物聚合酶链反应法结合琼脂糖电泳，根据PCR产物片段大小直接判定HBV基因型；应用PCR扩增全S基因序列-DNA测序-生物信息学分析方法确定部分样本的亚基因型，并探讨前前S区编码的流行情况。结果在217例可以通过混合性型特异性引物聚合酶链反应法确定基因型的感染者中，B型83例（38．2％）、C型71例（32．7％），B／C混合型63例（29．0％）。HBeAg阳性患者中感染B基因型占50％，B／C型混合感染占22％；抗-HBe阳性患者中B／C型混合感染36％，B型38％；在慢性乙型肝炎患者中，以B基因型多见（46％），在肝硬化和肝癌患者中，以C（41％和42％）或B／C混合基因型（38％和33％）感染为主；20例患者血清经过DNA测序-生物信息学分析方法确定了亚基因型，其中B2亚型2例，C2亚型18例，其中混合性型特异性引物聚合酶链反应判断为B型的4例经过测序分析为C2亚型。B2亚型不编码前前S区，18例C2亚型均编码前前S区。结论本研究提示厦门地区乙型肝炎患者群的HBV基因型B、C型的感染率大致相同，亚基因型分析提示C2亚基因型占90％，可能是B／C基因型重组的结果。C2亚基因型病毒株均编码前前S区，提示前前S区的编码可能具有亚基因型特异性。     

Molecular identification of hepatitis B virus genotypes/subgenotypes: Revised classification hurdles and updated resolutions

The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term “recombino-subgenotype”. Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term “immigro-subgenotype” to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.     

乙型肝炎e抗原阴性慢性乙型肝炎和肝硬化患者病毒基因型及丙氨酸氨基转移酶水平分析

目的观察乙型肝炎e抗原(HBeAg)阴性慢性乙型肝炎(CHB)及肝硬化患者的乙型肝炎病毒(HBV)基因型及丙氨酸氨基转移酶(ALT)水平。方法采用酶联免疫吸附法检测62例CHB和41例肝硬化患者HBV标志物和血清ALT水平,用聚合酶链反应法检测其HBV基因型。结果CHB患者中,21 例(33.9%)为HBeAg阴性,41例(66.1%)为HBeAg阳性;肝硬化患者中,28例(68.3%)为HBeAg阴性,13例(31.7%)为HBeAg阳性。CHB患者中,53例(85.5%)为C基因型,9例(14.5%)为B基因型; 肝硬化患者中39例(95.1%)为C基因型,2例(4.9%)为B基因型。HBeAg阴性CHB患者ALT>40 U/L 者的比例低于HBeAg阳性组(分别为47.6%和85.4%),差异有统计学意义(P<0.01)。HBeAg阴性肝硬化患者ALT>40 U/L者的比例低于HBeAg阳性组(分别为64.3%和92.3%)但差异无统计学意义。结论CHB 和肝硬化患者中,HBeAg阴性者的比例较高,此类患者的ALT水平较低,以C基因型占优势。     

HBsAg及HBV DNA定量水平在慢性乙型肝炎、肝硬化和肝癌患者中的变化

目的 了解HBsAg定量水平在慢性乙型肝炎、乙型肝炎肝硬化、HBsAg阳性的原发性肝癌患者中的变化及其在3组患者中与HBV DNA的相关性. 方法 采集47例慢性乙型肝炎患者(乙型肝炎组),72例乙型肝炎肝硬化患者(肝硬化组)及54例肝癌患者(肝癌组)的血清标本,用雅培化学发光法进行HBsAg定量测定,荧光PCR定量法检测HBV DNA量水平.多组分析采用Kruskal-Wallis检验,两组间比较采用Mann-WhitneyU检验,相关性分析采用Spearman检验.结果 HBsAg定量值在乙型肝炎、肝硬化、肝癌组患者中的中位数分别为2361.10、1001.64、594.35IU/ml,3组间呈逐渐下降趋势,x2= 24.394,P＜0.05,差异有统计学意义;乙型肝炎组与肝硬化组比较,Z= -3.754,P＜0.05,差异有统计学意义;乙型肝炎组与肝癌组比较,Z=-4.630,P＜0.05,差异有统计学意义;而肝硬化组与肝癌组比较,差异无统计学意义.HBeAg阳性患者,HBsAg定量值在乙型肝炎组、肝硬化组、肝癌组患者的中位数分别为3259.83、1077.30、789.72 IU/ml,3组间呈下降趋势,x2= 15.643,P＜0.01,差异有统计学意义.对于HBeAg阴性患者,HBsAg定量值在乙型肝炎组、肝硬化组、肝癌组患者的中位数分别为1669.00、1001.64、582.05 IU/ml,3组间呈下降趋势,x2 =6.423,P＜0.05,差异有统计学意义.HBV DNA定量值在乙型肝炎组、肝硬化组、肝癌组患者的中位数分别为5.3579、 4.2207、1.0000 log10拷贝/ml,4分位数间距分别为(4.3579 ～6.8745)、(0.0000 ～ 5.7393)、(0.0000 ～ 4.6651)log10拷贝/ml,3组HBV DNA定量值比较,x2=31.412,P＜0.05,差异有统计学意义; HBsAg与HBV DNA在乙型肝炎组(r= 0.297,P＜0.05)、肝硬化组(r= 0.346,P＜0.05)、肝癌组(r=0.452,P＜0.05)均呈正相关.结论 HBsAg定量值在慢性乙型肝炎、肝硬化、肝癌患者中逐渐降低,且与HBV DNA水平正相关.     

Impact of occult hepatitis B virus infection and prior hepatitis B virus infection on development of hepatocellular carcinoma in patients with liver cirrhosis due to hepatitis C virus

Objective. Although hepatitis B virus (HBV) DNA can be detected in liver or sera of patients without serum hepatitis B surface antigen (HBsAg), its clinical relevance in hepatocarcinogenesis remains controversial. This observational cohort study was conducted to clarify the risk factors, including the presence of serum HBV DNA and hepatitis B core antibody (anti-HBc), for hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). Material and methods. The study comprised 123 patients with LC due to HCV, and negative for HBsAg. The risk factors for HCC development were analyzed by univariate and multivariate analysis. Serum samples were assayed for HBV DNA using real-time polymerase chain reaction. Results. Serum HBV DNA was detectable in 14 patients (11.4%) and serum anti-HBc in 96 (78.0%). During the follow-up period (mean 53.3 months), 80 patients (65.0%) developed HCC. The cumulative HCC development rate was significantly higher in the anti-HBc-positive group than in the anti-HBc-negative group (p=0.0039), but did not differ between the serum HBV DNA-positive and -negative groups (p=0.8570). The multivariate analysis indicated that male gender, alpha-fetoprotein (AFP) 20 ng/ml or greater, average serum alanine aminotransferase (ALAT) 80 IU/l or greater and the presence of anti-HBc were independent risk factors for development of HCC (p=0.038, p=0.013, p=0.020 and p=0.001, respectively). Conclusions. Serum anti-HBc, which indicates a previous HBV infection, has clinical significance in hepatocarcinogenesis in patients with HCV-related LC, but serum HBV DNA does not. Therefore, anti-HBc in serum is a significant predictor for HCC.     

慢性HBV感染者HBsAg血清学清除后为什么还发生肝细胞癌?

本文综述了慢性HBV感染者HBsAg血清学清除后发生肝细胞癌的风险、机制及启示。     

Hepatitis B virus genotypes and subgenotypes in China

Eight Hepatitis B virus (HBV) genotypes (A to H) have been identified based on an intergenotype divergence of 8% or more in the entire nucleotide sequence. Subgenotypes have also been identified in different HBV genotypes. As a highly endemic area for HBV infection, the prevalence of chronic HBV infection in China is between 8 and 20% of the general population. Genotypes B and C were identified as the most common HBV strains and account for approximately 95% of Chinese patients. Further study confirmed all genotype B strains belong to subgenotype Ba. Two of genotype C subgenotypes, C1 (Cs) and C2 (Ce), were found in China and they showed different geographic distributions. Genotype A was very rarely found, while genotypes E, F, G and H have not beenreported until now. Two types of HBV C/Drecombinant viruses have been identified in west China and distinct geographic and ethnic distributions were observed. Significant differences were observed ( P  < 0.001) in the prevalence of A1896 and T1762/A1764 mutations among HBV Ba, C1 and C2 subgenotypes in Chinese patients. Accumulating evidence showed the response rate to antiviral therapy in Chinese patients is higher in genotype B than genotype C patients on interferon treatment, but no difference was observed on nucleoside/nucleotide analog treatment.     

Intrahepatic distribution of hepatitis B virus antigens in patients with and without hepatocellular carcinoma

AIM: To study the intrahepatic expression of hepatitis B surface antigen(HBs Ag) and hepatitis B core antigen(HBc Ag) in chronic hepatitis B patients with and without hepatocellular carcinoma. METHODS: A total of 33 chronic hepatitis B patients(mean age of 40.3 ± 2.5 years), comprising of 14 HBe Ag positive and 19 HBe Ag negative patients; and 13 patients with hepatitis B virus related hepatocellular carcinoma(mean age of 49.6 ± 4.7 years), were included in our study. Immunohistochemical staining for HBc Ag and HBs Ag was done using standard streptavidin-biotin-immunoperoxidase technique on paraffin-embedded liver biopsies. The HBc Agand HBs Ag staining distributions and patterns were described according to a modified classification system. RESULTS: Compared to the HBe Ag negative patients, the HBe Ag positive patients were younger, had higher mean HBV DNA and alanine transaminases levels. All the HBe Ag positive patients had intrahepatic HBc Ag staining; predominantly with "diffuse" distribution(79%) and "mixed cytoplasmic/nuclear " pattern(79%). In comparison, only 5% of the HBe Ag-negative patients had intrahepatic HBc Ag staining. However, the intrahepatic HBs Ag staining has wider distribution among the HBe Ag negative patients, namely; majority of the HBe Ag negative cases had "patchy" HBs Ag distribution compared to "rare" distribution among the HBe Ag positive cases. All but one patient with HCC were HBe Ag negative with either undetectable HBV DNA or very low level of viremia. Intrahepatic HBc Ag and HBs Ag were seen in 13(100%) and 10(77%) of the HCC patients respectively. Interestingly, among the 9 HCC patients on anti-viral therapy with suppressed HBV DNA, HBc Ag and HBs Ag were detected in tumor tissues but not the adjacent liver in 4(44%) and 1(11%) patient respectively. CONCLUSION: Isolated intrahepatic HBc Ag and HBs Ag can be present in tumors of patients with suppressed HBV DNA on antiviral therapy; that may predispose them to cancer development.