血管内皮生长因子936*T/C基因多态性与原发性肝癌的关系

目的 通过研究血管内皮生长因子(VEGF)936*T/C基因多态性与原发性肝癌之间的关系,了解该基因多态性对原发性肝癌生成及发展的影响.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法 检测原发性肝癌及正常对照的VEGF 936*T/C基因型.结果 原发性肝癌病人VEGF 936*T/C基因型或等位基因与对照组相比无差异(精确概率法计算基因型P=0.275;卡方检验等位基因χ2=0.877,P=0.349).在肿瘤直径≥8 cm的病人C/C基因型和c等位基因比例(66.7%和82.0%)明显大于肿瘤直径<8 cm病人的比例(40.0%和65.0%),两者差异有统计学意义(C/C基因型χ2=4.722,P=0.029;C等位基因χ2=5.393,P=0.020).结论 VEGF936*C/C基因型或936*C等位基因与原发性肝癌的生成无关,但VEGF 936*C/C基因型和C等位基因有助促进肿瘤的生长.     

162例HBV感染者的基因型分析及临床意义

目的 HBV基因型与HBV传播方式、临床疾病谱、疾病进展、病情预后、以及抗病毒疗效均有一定的相关性,本研究拟进一步探讨HBV感染者基因型的临床意义.方法 对我院162例HBV感染者进行HBV基因型分析,并对其肝功能、乙型肝炎病毒血清标志物(包括前-S1抗原)、HBVDNA定量和T细胞亚群等进行检测和分析.结果 HBV基因型存在地域分布,北方人基因型以C型为主,南方人基因型以B型为主.在无症状携带者或急性肝炎-慢性肝炎-肝硬化-肝癌的进展顺序中,基因型B的比例逐渐减少,而基因型C的比例则逐渐增多.基因型C和BC混合型的前白蛋白水平(前-A)、白蛋白水平(ALB)以及白蛋白/球蛋白比例(A/G)较基因型B显著降低(分别为P=0.03、P=0.03、P=0.01和P=0.005、P=0.001、P＜0.001),基因型C的胆碱酯酶(CHE)水平较基因型B降显著低,基因型C和BC混合型的球蛋白水平(GLO)较基因型B显著增加(分别为P＜0.001和P=0.013);而在ALT、AST、TBil、GGT、ALP和TBA水平则差异不显著(P＞0.05).基因型C和BC混合型的HBV感染者中,前-S1抗原阳性率较高(分别为71.3%和66.7%),而基因型B的则低(阳性率30%);相反,基因型B的HBV感染者前-S1抗原阴性率高(66.7%),而基因型C和BC混合型的前-S1抗原阴性率低(分别为26.6%和25.9%).结论 HBV感染者的HBV基因型存在地域分布,基因型C较基因型B的肝功能损害严重,进展为慢性肝炎、肝硬化、肝癌的比例高.基因型C的前-S1抗原阳性率较高,基因型B的前-S1抗原阴性率高,它们的相关关系有待进一步研究.     

慢性乙型肝炎病毒感染者病毒基因型分布及其与肝纤维化和肝细胞癌的关系

目的 调查浙江省杭州地区慢性乙型肝炎病毒(HBV)感染者的HBV基因型分布,并分析基因型与肝纤维化和肝细胞癌的关系.方法 回顾性分析2007年6月至2012年6月在杭州市第一人民医院就诊的190例慢性HBV感染者的血清学、病毒学指标和临床病理学资料.190例患者根据病理及相关检测分为慢性乙型肝炎(CHB)组(62例)、肝硬化组(60例)和肝细胞癌组(68例).HBV基因型测定采用多重PCR扩增,基因亚型测定采用PCR扩增结合限制性片段长度多态性(RFLP)方法.采用SPSS 11.0软件进行统计学分析.结果 190例慢性HBV感染者中,B基因型感染61例(32.1％),C基因型感染126例(66.3％),3例为B、C基因混合型感染.其中,B基因型全部为B2亚型,C基因型中C2亚型占绝对优势(97.6％,123/126).B基因型在CHB组的比例(46.8％,29/62)高于肝硬化组(20.0％,12/60)和肝细胞癌组(29.4％,20/68)(x2=8.73和4.16,P＜0.01或＜0.05);C基因型在肝硬化组和肝细胞癌组的比例高于CHB组(x2=9.54和4.17,P＜0.01或＜0.05).三组患者中感染C2基因亚型的血清透明质酸(HA)水平高于感染B2基因亚型的患者(t=2.685,2.433和2.015,P＜0.01或＜0.05).CHB患者中感染C2基因亚型者比感染B2基因亚型者有更高的肝纤维化分期(x2=6.726,P=0.010),而肝脏炎症分级差异无统计学意义(x2=0.601,P＞0.05).肝细胞癌患者中,感染B2基因亚型者肿瘤直径≥5 cm的比例更高(x2=7.231,P＜0.01),感染C2基因型者伴肝硬化更常见(x2 =4.910,P＜0.05).结论 浙江省杭州地区CHB患者以C2和B2基因亚型为主.感染C2基因亚型的患者可能更易发展为严重肝纤维化,而感染B2基因亚型的患者和大肝癌相关.     

湖南省怀化市少数民族及汉族慢性乙型肝炎患者病毒基因分型及临床分析

目的 了解湖南省怀化市少数民族及汉族慢性乙型肝炎患者病毒基因型分布特点及不同基因型与临床肝病的相关性.方法 采用S基因序列分析法对湖南省怀化市111例慢性乙型肝炎患者进行乙型肝炎病毒基因分型,并分析相关流行病学、病例构成、HBV DNA载量、HBeAg阳性率及肝功能情况.结果 该地区111例慢性乙型肝炎患者HBV基因型检测到B型及C型,其中B型90例(81.08%),C型19例(17.12%),2例(1.80%)无法分型. B、C基因型分布情况:33例少数民族组患者B基因型31例(93.93%),C型2例(6.07%);76例汉族组患者B基因型59例(77.63%),C基因型17例(22.37%).C基因型患者肝硬化及肝癌构成比高于B基因型患者,HBV DNA载量、HBeAg阳性率及球蛋白水平高于B基因型,而白蛋白水平低于B基因型.结论 该地区乙型肝炎病毒基因型以B型为优势基因型,少数民族与汉族患者HBV基因型构成有显著差异,C基因型患者HBeAg血清转换率低,可能较易发生肝病进展.     

乙肝相关性肝癌病人在根治术后的复发和生存分析——病例对照研究

目的:探讨乙型肝炎病毒(HBV)感染对原发性肝细胞肝癌病人行根治术后复发和生存的影响。方法:回顾性观察2005年至2008年我科按照HBV抗原阳性和HBV五项(包括丙肝)全阴性,将肝癌病人分为HBV组(n=79)和非HBV组(n=79)。按年龄、性别、肿瘤直径、血管侵犯及肿瘤数目进行1∶1配对研究,分析两组间临床病理资料的特点,以复发和死亡作为终点事件,对外科治疗的复发率、生存率及预后相关危险因素进行分析总结。结果:HBV组1、3和5年总体复发率和生存率分别为48%、80%、85%和75%、41%、35%;非HBV组1、3和5年总体复发率和生存率分别为27%、65%、76%和86%、58%、44%;两者有统计学差异,HBV组复发率高于非HBV组(P=0.012),而生存率低于非HBV组(P=0.010)。经COX风险比例模型分析后发现HBV阳性、肿瘤多发、血管侵犯、包膜侵犯和TNM分期是影响肝癌术后复发的危险因素;HBV阳性、肿瘤多发、术中输血、血管侵犯、包膜侵犯和TNM分期是影响肝癌术后生存的危险因素。结论:HBV相关性肝癌病人比HBV阴性肝癌病人术后的复发率高,生存率低。     

上海地区慢性乙型肝炎患者HBV基因型特点分析

目的 探讨上海市乙型肝炎病毒(HBV)基因型分布及与HBV感染患者的临床意义.方法 选择2005年2月至2006年2月上海华山医院门诊及住院患者中HBV DNA阳性(荧光定量PCR法)的HBV感染者45例,采用S基因序列分析法检测HBV基因型,并分析相应的前-C/C基因序列特点.根据患者的HBV标志物和HBV DNA水平判断不同基因型与疾病的相关性.结果 45例HBV感染者中基因型B共15例,C型30例,无A、D、E、F、G、H基因型.15例HBV/B均为Ba亚型,其中2例的前-C/C基因与HBV/C在nt 1975～nt 2293之间发生重组.HBV/C的HBeAg阳性率显著高于HBV/B(分别为83.3%,33.3%;P＜0.05),抗-HBe阳性率则显著低(分别为53.3%,73.3%;P=0.02).2种基因型的HBV DNA水平无显著差异.结论 本次抽样检查结果中HBV基因型为B型和C型,以C型为主,未发现A、D、E、F、G、H型.HBV/C型与B型相比有较高的HBeAg阳性率和较低的抗-HBe阳性率.     

乙型肝炎病毒基因型与肝细胞肝癌关系的研究

目的 探讨HBsAg阳性肝细胞肝癌(HCC)患者乙型肝炎病毒(HBV)DNA基因型与其患HCC之间的关系.方法 运用PCR条带分析与基因测序相结合的方法对我院500例HBsAg阳性患者(其中HCC患者150例)的HBV DNA进行分型,并对分型结果进行分析.结果 HBV DNA B型和C型基因型是HBsAg阳性HCC患者和非HCC患者的共同优势基因型.但HCC患者中C型基因型所占比例为65.33%(98/150),明显高于非HCC患者的25.14%(88/350),而B型则相反,分别为28.67%(43/150)与68.86%(241/350),x2=75.45,P<0.05.HCC患者中,HBV的B型与C型基因型分布在不同性别及不同年龄段之间的差异无统计学意义(P>0.05).结论 HBV DNA C型基因型在HCC患者中多见,可能与HCC的发生有关.     

乙型肝炎病毒基因型及S、P基因变异与肝移植术后乙型肝炎病毒感染的关系

目的 探讨乙型肝炎病毒(HBV)基因型和S、P基因变异与肝移植术后HBV再感染的关系.方法 因乙型肝炎相关终末期肝病接受肝移植,术后随访1.5～3年,发生HBV再感染者14例(再感染组),移植前服用拉米夫定,移植后采用拉米夫定和抗乙型肝炎球蛋白(HBIG)预防HBV再感染.采用聚合酶链反应测定血清中HBV DNA水平,基因测序法分析HBV基因型、S基因及P基因变异,微粒子捕捉酶免法检测血清HBIG浓度.随机选取同期因乙型肝炎相关终末期肝病接受肝移植而未发生HBV再感染者20例为对照.结果 再感染组移植前血清HBV DNA≥103拷贝/ml者占71.4%,明显高于对照组的30%(P<0.05).再感染组移植前HBV基因型有B型(2例)和C型(12例),移植后基因型不变;对照组B型11例,C型9例.再感染组3例术前发生拉米夫定耐药位点变异者,9例C型者在P区拉米夫定耐药位点变异以外发生多位点氨基酸变异,且变异位点差异较大.再感染组50%的患者HBIG浓度为0,其S区"a-决定簇"的基因均发生变异.结论 乙型肝炎相关终末期肝病患者肝移植后的HBV再感染与HBV基因型有关,C基因型者更易发生HBV再感染;再感染可能与P基因区存在多位点变异及S区的"a-决定簇"基因变异密切相关.     

HBV基因B型感染者不同病程反转录酶区预存变异的研究

目的 比较不同病程阶段的慢性肝病患者HBV反转录酶区(RT)预存变异的情况.方法 收集201 1年1月至2013年6月浙江省上虞市人民医院和浙江大学医学院附属第一医院收治的慢性肝病患者474例,其中慢性乙型肝炎(CHB)组205例,肝硬化组153例和肝癌组116例,所有患者均未接受过核苷(酸)类药物抗病毒治疗.采用PCR后直接测序法检测HBV RT区变异,同时确定基因型.应用SPSS 14.0软件进行统计学分析.结果 患者以HBV基因B型为主,共387例(81.6％),其中CHB组156例,肝硬化组124例,肝癌组107例.387例B基因型患者均存在核苷(酸)类药物耐药变异位点,HBV RT区rtS106C变异阳性率在CHB组(14.1％,22/156)和肝硬化组(14.5％,18/124)高于肝癌组(4.7％,5/107)患者(x2=6.126和6.207,P值均＜0.05);rtD134E/G/N/S变异阳性率在CHB组(21.8％,34/156)和肝硬化组(20.2％,25/124)高于肝癌组(10.3％,11/107)(x2=5.933和4.263,P值均＜0.05).HBV RT区rtD134E/G/N/S和rtS106C变异与HBeAg和性别有一定的关系,而与HBV DNA载量和年龄无关.CHB组(5.3％,157/2964)和肝硬化组(5.6％,132/2356)的HBV RT区A-B间域的变异频率高于肝癌组(3.5％,71/2033)(x2=9.018和11.018,P值均＜0.01).结论 未接受核苷(酸)类药物抗病毒治疗的不同阶段慢性肝病患者均可能存在核苷(酸)类药物耐药相关变异.HBV RT区rtS106C和rtD 134E/G/N/S变异可能与不同阶段慢性肝病中严重免疫应答引起的活动性炎症坏死有关.HBV RT区的A-B间域变异可能与炎症坏死、免疫反应和肝纤维化进展有关.     

肝癌多中心发生与肝内转移的临床病理学差异研究

目的 探讨HBV相关的多结节肝癌病人中,多中心发生与肝内转移肝癌的发病情况和两种类型肝癌的临床病理学差异因素.方法 收集天津医科大学附属肿瘤医院经手术切除的多结节肝癌病人的临床病理资料.根据多结节肝癌的病理学特征,分为多中心发生组和肝内转移组,统计学分析两种类型肝癌的差异因素和预后.结果 89例多结节肝癌病人中,16例(18.0%)为多中心发生,57例(64.0%)为肝内转移;逐步回归多因素分析显示肿瘤分级、肿瘤大小、胆碱酯酶、Child's分级和门静脉侵犯在两组间差异显著(P<0.05);多中心发生组的总体生存情况优于肝内转移型病人(P=0.003);多发肿瘤类型(多中心发生或肝内转移)和Child's分级是独立的预后因素.结论 笔者收治的HBV相关的多结节肝癌,以肝内转移型肝癌为主,多中心发生型肝癌比例较低,对于多中心发生的病人,应积极手术切除.其预后优于肝内转移者.临床医生可以通过肿瘤分级、肿瘤大小、胆碱酯酶、Child's分级和门静脉侵犯评价多结节肝癌的类型.     

乙肝相关性肝细胞癌患者血清外泌体miR-1290 水平的变化及其诊断价值

目的:探讨乙型肝炎病毒(HBV)相关性肝细胞癌(HCC)患者血清外泌体miR-1290水平的变化及其诊断价值。方法:收集31例HBV相关HCC患者,20例HBV携带患者,20例乙型肝炎肝硬化患者以及19例健康体检者的血液样本,分离纯化血清外泌体并鉴定,用RT-PCR检测外泌体miR-1290水平。利用ROC曲线评价外泌体miR-1290对HBV相关HCC的诊断效能。结果:纯化提取的样品中含有大量外泌体颗粒,并且具备外泌体的典型特性。与健康个体比较,外泌体miR-1290水平在HBV携带患者中未见明显差异(P0.05)在HBV相关HCC患者中明显升高(P0.001),且晚期HCC患者高于早期HCC患者(P=0.036),而在乙型肝炎肝硬化患者中明显降低(P=0.006)。外泌体miR-1290的ROC曲线的曲线下面积(AUC)为0.82(95%CI=0.73～0.91),具有较好的特异性(88.1%),且其诊断效能优于AFP(AUC=0.792)。结论:血清外泌体miR-1290在HBV相关HCC患者中升高,对HBV相关HCC具有较好的诊断效能,并有望成为诊断HBV相关HCC的血清学标志物。     

Significance of Hepatitis B Virus Genotype in Liver Transplantation for Chronic Hepatitis B

Hepatitis B virus (HBV) genotype influences chronic hepatitis B disease profile but its relevance in liver transplantation (LTx) is not known. HBV genotype was identified by direct sequencing from pre-transplant sera of 119 patients who underwent LTx using lamivudine prophylaxis (genotype A,1; B,43; C,74; D,1). The baseline characteristics and outcome of 43 genotype B and 74 genotype C patients were compared. Genotype B patients had significantly more pre-transplant acute flare, worse liver functions and higher model for end-stage liver disease score. Fewer genotype B patients had HBeAg (13% vs. 32%; p=0.017), but HBV DNA seropositivity (by bDNA assay) was comparable (26% vs. 23%; p=0.727). The 3-year graft survival was 83% for genotype B and 89% for genotype C (p=0.2). The rate of HBsAg clearance or seroreversion was the same. The cumulative rate of viral breakthrough due to lamivudine-resistant mutants at 3 years was 4% for genotype B and 21% for genotype C (p=0.017). Liver biopsy after viral breakthrough showed recurrent hepatitis B in 7 of 10 genotype C patients, including 2 with fibrosing cholestatic hepatitis, and no histologic recurrence in 2 genotype B patients. In conclusion, HBV genotypes B and C are associated with different patterns of end-stage liver diseases that required transplantation, and genotype C may carry a greater risk and severity of recurrence due to lamivudine-resistant mutants.     

肝移植治疗乙肝相关疾病

目的 总结原位肝移植（OLT）治疗乙肝相关疾病的疗效,并评价了拉米夫定对肝移植术后乙肝复发的防治作用。方法 自1993年4月-2000年12月,中山医科大学器官移植中心为54例乙肝相关疾病患者实施了肝移植,其中乙肝坏死后肝硬化17例,为第1组,25例同时合并肝癌者为第2组、其余12例暴发性肝功能衰竭患者为3组。回顾性地分析了3组患者术后存活率、早期死亡原因以及拉米夫定对术后乙肝复发的防治情况。结果 乙肝相关疾病患者肝移植术后早期存活率为75.9%,暴发性肝衰组患者术后早期并发症发生率明显高于其它2组;OLT对小肝癌患者的疗效明显优于大肝癌患者;拉米夫定防治乙肝复发辣效好且未发现副作用。结论 结合拉米夫定,OLT是治疗暴发性乙肝、乙肝肝硬化及小肝癌甚或某些选择性大肝癌患者的有效手段。     

miR-22启动子区域的遗传变异与HBV相关肝癌发病风险的关系

目的：探讨微小RNA 22（miR-22）启动子区域的遗传变异与中国人群乙型肝炎病毒（HBV）相关肝癌易感性的关系。方法：采用病例-对照方法,收集1 020例确诊的乙型肝炎病毒（HBV）阳性HCC患者（病例组）和1 046例健康对照个体（对照组）静脉血标本。用TaqMan等位基因分型方法对miR-22启动子区域多态位点rs6502892（C→T）和rs721576（A→G）进行基因型检测,结合研究对象的基本资料,应用Logistic回归法分析不同基因型与HBV相关肝癌发病风险的关系。结果：rs6502892的基因型分布在病例组与对照组间差异有统计学意义（P=0.018）,而rs721576的基因型的分布在两组间差异无统计学意义（P>0.05）。与rs6502892野生型（CC）比较,rs6502892突变基因型（CT/TT）的HBV相关肝癌的发病风险明显增加（调整后OR=1.23,95% CI=1.02~1.47,P=0.029）。进一步的分层分析表明,rs6502892突变基因型（CT/TT）的危险效应在52岁以下年龄组、女性、吸烟者和饮酒者中更明显（均P<0.05）;而rs721576突变基因型（AG/GG）在男性和非吸烟者中HBV相关肝癌的发病风险降低（均P<0.05）。结论：miR-22 rs6502892突变基因型（CT/TT）增加中国人群HBV相关肝癌的发病风险,而rs721576突变基因型（AG/GG）降低男性和非吸烟者患HBV相关肝癌的风险。这一结论有待进一步的关联研究以及功能学研究的证实。

     

Preliminary results: Outcome of liver transplantation for hepatitis B virus varies by hepatitis B virus genotype

Hepatitis B virus (HBV) is a leading cause of liver failure throughout the world. HBV has seven different genotypes based on variations within the viral nucleotide sequence. Initially, patients who underwent liver transplantation for HBV had high recurrence rates and poor survival. Recently, improved outcomes have been reported when patients are administered hepatitis B immunoglobulin (HBIg) infusions to maintain high serum hepatitis B surface antibody titers after transplantation. Unfortunately, recurrence rates are still high in patients with active pretransplant HBV replication. The aims of this study are to evaluate the impact of HBV genotype on pretransplantation HBV replication and posttransplantation HBV recurrence rate, morbidity, and mortality. Sera from 22 patients who underwent transplantation for HBV at our center were tested for HBV genotype by an enzyme-linked immunosorbent assay technique using monoclonal antibodies to the pre-S2 region. All patients were administered HBIg after transplantation; 5 patients were administered both lamivudine and HBIg. HBV genotypes were distributed as follows: genotype A (10 patients), genotype C (6 patients), genotype D (5 patients), and genotype E (1 patient). Pretransplantation HBV replication was most common with genotype A (80%), whereas less so with genotypes C (33%) and D (40%). Nine patients (41%) developed recurrent HBV infection: genotype A (2 patients; 20%), genotype C (3 patients; 50%), and genotype D (4 patients; 80%). Mortality was greatest with genotype D (40%). Our data suggest that patients with genotype A have the lowest risk for HBV recurrence despite having the highest rate of pretransplantation HBV viral replication. Patients with genotype D appear to have the highest risk for HBV recurrence and mortality. Additional larger multicenter studies are needed to confirm these findings. (Liver Transpl 2002;8:550-555.)     

Comparison of Surgical Outcomes for Hepatocellular Carcinoma in Patients With Hepatitis B Versus Hepatitis C: A Western Experience

Background: We reviewed our experience in patients with hepatocellular carcinoma (HCC) and chronic hepatitis to determine if differences exist in preoperative status and postoperative survival between those with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections.Methods: We reviewed the records of 240 consecutive patients with HCC who underwent hepatic resection or liver transplantation at Mount Sinai Hospital between February 1990 and February 1998. Patients who tested negative for hepatitis B antigen and hepatitis C antibody (74 patients) as well as those who tested positive for both (2 patients) were excluded. Age as well as preoperative platelet count, prothrombin time (PT), albumin, and total bilirubin were measured in all patients. The presence of encephalopathy or ascites also was noted. Explanted livers and resection specimens were examined for size, number, and differentiation of tumors as well as the presence of vascular invasion and cirrhosis in the surrounding parenchyma.Results: One hundred twenty-one patients with HCC tested positive for HCV, and 43 tested positive for HBV. A significantly higher proportion of patients with HCV required transplant for the treatment of their HCC when compared to those with HBV. In the resection group, patients with HCV were significantly older that those with HBV. They also had significantly lower mean preoperative platelet counts and albumin levels and higher mean PT and total bilirubin levels. Resected patients with HCV had significantly less-differentiated tumors and a higher incidence of vascular invasion and cirrhosis when compared to those with HBV. There was no statistical difference in the multicentricity and size of tumors between the two groups. The 5-year disease-free survival was significantly higher for HBV patients treated with resection when compared to those with HCV (49% vs. 7%, P 5 .0480). Patients with HCC and HCV had significantly longer 5-year disease-free survival with transplant when compared to resection (48% vs. 7%, P 5 .0001).Transplanted patients with HBV and HCC had preoperative status, pathological findings, and survival similar to those of patients with HCV.Conclusions: Based on preoperative liver function and tumor location, a much higher proportion of HCC patients with HBV were candidates for resection. Significant differences in preoperative status, tumor characteristics and disease-free survival exist between HCC patients with chronic HBV and HCV infection who have not yet reached end-stage liver disease. Serious consideration should be given to transplanting resectable HCC with concomitant HCV, especially in cases with small tumors.Presented at the 52nd Annual Meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

Hepatitis B Prophylaxis Using Lamivudine and Individualized Low-dose Hepatitis B Immunoglobulin in Living Donor Liver Transplantation

Background

Currently, most available experience concerning prophylaxis against hepatitis B virus (HBV) recurrence after living donor liver transplantation (LDLT) is limited to studies of small size and short follow-up. The objective of this study was to evaluate the efficacy of a prophylactic regimen using lamivudine and individualized low-dose intramuscular hepatitis B immunoglobulin (HBIG) in LDLT.

Methods

We used a database of adult-to-adult right-lobe LDLT procedures performed from June 2002 to April 2012 at our center for HBV-related end-stage liver diseases. Patients were divided into 3 groups: group A, HBV-related decompensated liver cirrhosis; group B, fulminant hepatitis B; and group C, hepatocellular carcinoma (HCC).

Results

During a mean follow-up of 38.3 ± 28.9 months, 8 of 165 (4.8%) recipients developed HBV recurrences. The mean time for HBV reinfection was 15.8 + 11.0 months after transplantation. The overall 1-, 3-, and 5-year HBV recurrence rates were 3%, 7%, and 8.2%, respectively. Both patients with fulminant hepatitis B or HCC seemed to have higher rates of HBV recurrence than those with decompensated liver cirrhosis, albeit not significantly. The independent predictor of HBV recurrence was high HBV DNA level (≥10⁵ copies/mL) at LDLT.

Conclusions

Lamivudine and individualized low-dose intramuscular HBIG provides effective prophylaxis against HBV recurrence after LDLT. Pre-LDLT HBV DNA of ≥ 10⁵ copies/mL was associated with HBV recurrence.     

慢性乙型肝炎和肝硬化及肝癌与HLA-DQA1基因多态性关系的研究

目的:研究HLA-DQA1等位基因多态性与慢性乙型肝炎(HBV)病毒感染、肝硬化及肝癌的关系。方法:采用聚合酶链序列特异性引物(PCR-SSP)技术分别对168例慢性HBV感染者(包括48例慢性乙型肝炎、42例乙型肝炎肝硬化和78例乙型肝炎后肝癌患者)以及100例对照(感染后自发恢复者)进行HLA-DQA1等位基因的检测。结果:慢性HBV感染者HLA-DQA1*0102的表型频率显著低于对照组(25.6%vs47.0%,OR=0.39,Pc=0.003),DQA1*0601表型频率高于对照组(4.2%vs0,OR=0.96,P=0.039),但后者差异无统计学意义(Pc>0.05)。肝硬化患者DQA1*0104的表型频率显著低于无肝硬化患者(6.4%vs28.4%,OR=0.17,Pc=0.001),DQA1*0201的表型频率高于无肝硬化患者(27.7%vs12.2%,OR=2.76,P=0.014),但后者差异无统计学意义(Pc>0.05)。HLA-DQA1各等位基因的表型频率在肝癌患者与非肝癌患者间差异无统计学意义。结论:HLA-DQA1*0102等位基因可能降低慢性HBV感染的风险,而DQA1*0104等位基因可能降低乙型肝炎肝硬化的风险。乙型肝炎后肝癌的发生与HLA-DQA1等位基因无明显相关性。     

乙肝相关性肝癌和丙肝相关性肝癌的临床病理特征及意义

【摘要】〓目的〓探讨乙肝相关性肝癌和丙肝相关性肝癌在临床病理特征的差异,以及这些差异的临床意义和对预后的影响。方法〓收集2003年12月~2010年10月在南方医科大学附属南方医院行手术治疗C-HCC标本18例和2011年3月~2012年12月行手术治疗的B-HCC标本34例,以及这些肝癌患者的临床病理资料。分析乙肝相关性肝癌和丙肝相关性肝癌在临床病理特征的差异,以及这些差异的临床意义和对预后的影响。结果〓乙肝相关性肝癌平均年龄(46.9±10.5)显著低于丙肝相关性肝癌组(59.0±9.9),平均住院天数(17.9±6.8)显著低于丙肝相关性肝癌组(34.9±16.5),平均术后住院天数(11.5±4.3)显著低于丙肝相关性肝癌组(19.4±11.9),肝功能分级中A级肝功明显较丙肝相关性肝癌组多,最大肿瘤直径明显大于丙肝相关性肝癌组,差异均有统计学意义(P<0.05)。B-HCC组患者中位无瘤生存时间为13个月,1年、2年无瘤生存率分别为56.3%和32.0%;C-HCC组患者中位无瘤生存时间为16.5个月,1年、2年无瘤生存率分别为75%和75%。Cox模型分析提示肝炎类型是肝细胞癌术后复发的独立影响因素。乙肝相关肝细胞癌术后复发的风险是丙肝相关性肝癌的2.35倍(P=0.108)。结论〓乙肝病毒与丙肝病毒相关肝细胞癌的临床病理特征及预后有显著差异。乙肝相关性肝癌术后恢复较丙肝相关性肝癌快,而丙肝相关肝细胞癌术后复发风险低于乙肝相关肝细胞癌。     

Comparison of clinical outcomes in chronic hepatitis B liver transplant candidates with and without hepatocellular carcinoma.

Patients with hepatocellular carcinoma (HCC) receive a higher MELD score and may undergo liver transplantation (OLT) earlier compared to patients with cirrhosis, potentially decreasing waiting list mortality. However, post-OLT survival may be reduced by recurrence of HCC. We compared clinical outcomes between patients with HBV-cirrhosis and no HCC and patients with HBV-HCC. A total of 279 patients (HBV-cirrhosis = 183; HBV-HCC = 96) in the US HBV-OLT study were followed for a median of 30.2 months from listing. Patients with HCC were older, more likely to be Asian, and had less severe liver impairment than patients with HBV-cirrhosis. Despite a higher rate of OLT in patients with HCC (78.1% vs. 51.4%; P < 0.001), intention-to-treat (ITT) survival (73% vs. 78%) and survival without OLT (82% vs. 79%) at 5 years were similar for patients with and without HCC. Cox regression analysis identified higher albumin, lower MELD, no HCC at listing, and being transplanted to be associated with better ITT survival. Ninety-four patients with HCC (including 19 new HCC) and 75 with HBV-cirrhosis underwent OLT. Post-OLT survival (83% vs. 90%) and HBV recurrence (11% vs. 10%) at 3 years were similar, while disease (HBV and/or HCC) recurrence (19% vs. 10%; P = 0.043) was higher in patients with HBV-HCC vs. HBV-cirrhosis. Disease recurrence was the only independent predictor of post-OLT survival. In conclusion, despite more advanced liver disease and a lower rate of transplantation, ITT survival of patients listed for HBV-cirrhosis was comparable to those with HBV-HCC, possibly related to beneficial effects of antiviral therapy.