肝移植术后乙型肝炎复发的原因及防治

乙肝复发是影响肝移植成功的重要因素,未作预防的乙肝病毒(HBV)感染者移植术后HBV的再感染率在80%以上,居乙肝肝硬化肝移植后死亡原因的首位.近年来,许多新的防治策略明显降低了该类患者术后的乙肝复发率.本文就肝移植术后乙肝复发的原因及防治作一综述.     

肝移植后乙肝复发的预防和治疗

目的 总结肝移植后预防乙肝复发的治疗方法和预防措施.方法 在肝移植手术前后,联合采用拉米夫定及乙肝免疫球蛋白预防乙肝病毒的再感染和复发,与只采用拉米夫定预防的对照组在治疗效果上进行对比.结果 对观察组使用拉米夫定配合乙肝免疫球蛋白的预防方法后,患者HBsAg水平的转阴率、乙肝病毒再感染率、复发率和 YMDD 变异率都明显低于对照组,且两组之间的差别具有统计学意义,P<0.05.结论 联合采用拉米夫定及乙肝免疫球蛋白预防肝移植术后乙肝复发的疗效显著,并且治疗费用低,符合当前我国国情,应在临床上进行推广使用.     

乙型肝炎相关肝病肝移植患者HBV复发因素临床分析

目的:探讨拉米夫定联合小剂量乙肝免疫球蛋白防治乙型肝炎相关肝病肝移植后HBV复发的影响因素。方法:对21例乙型肝炎相关肝病肝移植前后应用拉米夫定与小剂量乙肝免疫球蛋白预防HBV复发。结果:肝移植后6、12、24个月随访显示HBV复发率分别为14.3%(3/21)、11.8%(2/17)、11.1%(1/9)。3例HBV复发的病例显示:术前HBeAg(+)者较HBeAg(-)者易出现HBV复发(2χ=3.85,P<0.05)有统计学意义;而3例HBV复发的病例均为活动性乙型肝炎肝硬化,其中2例伴原发性肝癌;HBV复发的病例术中平均失血与未复发者相比有差异(两者分别为2063.2±427.4ml与2981.5±863.3ml)。结论:拉米夫定联合小剂量乙肝免疫球蛋白能有效地防治乙型肝炎相关肝病肝移植后HBV复发。术前HBV复制活跃者、乙型肝炎伴原发性肝癌、术中出血及输血量多是影响HBV复发的因素之一。     

乙肝免疫球蛋白预防肝移植后乙肝复发

目的探讨肝移植术后乙肝复发的预防方法,提高乙肝相关疾病患者肝移植的疗效。方法对120例成人乙肝患者肝移植的临床资料进行回顾性研究,比较小剂量HBIG Lamivudine与单纯应用Lamivudine预防肝移植术后乙肝复发的区别。结果Lamivudine组75例患者,12例患者发现有肝炎复发,复发率为16.7%(12/75),其中4例检测到YMDD变异株。联合用药组45例患者有3例乙肝复发,复发率为6.7%(3/45),未检测到YMDD变异株。结论小剂量HBIG Lamivudine比单纯使用Lamivudine能更有效预防肝移植术后乙肝复发,且术后发生YMDD变异的危险性降低。     

肝移植术后防治乙肝复发的策略

目的 探讨乙肝标志物阳性患者行肝肝移植治疗后如何防治乙肝复发的问题。方法 回顾性分析该研究院2000年10月-2003年10月40例乙肝病毒相关终末期肝病肝移植术后，联合应用乙肝免疫球蛋白和Lamivudine对预防乙肝病毒复发的疗效。结果 40例患者随访12-36个月，2例肝癌肝移植患者因肝癌复发分别于移植后8个月和13个月死亡。术后2周31例患者HBsAg、HBeAg及HBV-DNA均为阴性：6例因经济原因未能继续使用Lamivudine和HBIG的患者术后2-9个月HBsAg阳性，并出现明显的肝功能损害，经加用Lamivudine和HBIG并护肝治疗后转阴．肝功能明显好转；3例在术后4个月内HBV-DNA、HBsAg和HBeAg阳性。4个月后HBV-DNA降至10^4 copies／mL以下，HBsAg转阴。肝功能良好。结论 乙肝病毒相关终末期肝病肝移植术后，联合应用乙肝免疫球蛋白和Lamivudine对预防乙肝病毒复发有良好的疗效。     

肝移植术后长期联合应用拉米夫定和小剂量乙肝免疫球蛋白预防乙型肝炎复发的疗效

目的评估肝移植术后长期联合应用拉米夫定(LAM)和小剂量乙肝免疫球蛋白(HBIG)预防乙型肝炎复发的疗效,探讨肝移植术后乙型肝炎病毒(HBV)再感染和乙型肝炎复发的长期联合预防方案。方法通过前瞻性研究中山大学附属第三医院肝脏移植中心1993年10月至2005年8月符合研究标准的190例肝移植,术后应用拉米夫定联合小剂量乙肝免疫球蛋白预防,出现LAM耐药时加用阿德福维(ADV)。依据乙肝病毒标志物、HBVDNA定量、YMDD变异、生化指标和组织病理学检查诊断HBV再感染和乙型肝炎复发。结果190例中出现再感染15例(7.9%),其中肝炎复发7例,加用ADV治疗好转5例,再移植2例;其余HBV再感染8例均加用ADV治疗,血清HBVDNA水平下降5例,转为阴性3例;HBsAg阴转1例。随访时间12～34个月,平均再感染时间8.3月。结论长期联合应用拉米夫定和小剂量乙肝免疫球蛋白可有效预防乙型肝炎复发,加用阿德福维可有效治疗拉米夫定耐药。     

肝脏移植术后乙肝病毒复发和再感染的防治

HBV感染患者肝移植术后乙肝复发和再感染是导致移植物功能丧失和患者死亡的重要原因之一.目前乙肝复发和再感染的防治措施包括:被动免疫、主动免疫、抗病毒治疗以及联合治疗.     

拉米夫定联合乙型肝炎免疫球蛋白防治肝移植术后乙型肝炎复发的疗效研究

多项研究结果显示,肝移植术后乙型肝炎(下文简称乙肝)复发(指术后乙肝表面抗原阳性时间持续超过3周或转阴后又重新转阳)是导致其术后死亡的主要原因川.近年来随着乙肝免疫球蛋白及核苷类药物的应用,乙肝复发率已明显降低,但长期应用拉米夫定易增加乙肝病毒(HBV)变异的危险性,且术前发生YMDD变异与术后乙肝复发率有明显相关性;同时,大剂量长期应用乙肝免疫球蛋白不仅价格昂贵,且同样易造成HBV基因突变.     

肝移植术后预防乙肝复发的治疗进展

世界上首例肝移植术是由Starl在1967年成功完成的[1],10年后,我国第1例肝移植术在上海瑞金医院获得成功。此后,肝移植作为各种终末期肝病和肝功能衰竭唯一有效治疗方法,越来越多受到肝外科大夫的青睐[2]。在我国乙肝患者众多,乙肝患者占肝移植病人总数的80%以上。肝移植术后乙肝复发严重威胁移植肝及患者的存活率。未接受乙肝预防治疗的患者术后乙肝复发几率高达     

肝移植术后乙型肝炎患者再感染和复发的预防

目的 探讨乙型肝炎相关疾病患者行肝移植术后乙肝再感染和复发的预防措施.方法 选择符合条件的37例病例,术前开始口服拉米夫定,术中应用乙肝免疫球蛋白,术后联合应用拉米夫定和乙肝免疫球蛋白,观察术后1 a内乙肝再感染和复发的情况.结果 术后1 a内乙肝再感染率为16.2%,乙肝复发率为5.4%.结论 小剂量乙肝免疫球蛋白与拉米夫定联合应用可有效地预防肝移植术后乙型肝炎的再感染和复发.     

LIVER TRANSPLANTATION IN PATIENTS WITH FULMINANT HEPATITIS B：EXPERIENCE IN CANTON,CHINA

INTRODUCTIONFulminanthepatitisB（FHB）isaseriousdiseaseinAsia，particularlyinChinawithhighincidence，whichusuallyleadstoencephalopathywithan８０percentmor－talityrate．Themostfrequentcauseofdeathiscerebraledemafollowedbyblood－barrierpermeabilityimpairmen     

Liver transplantation at the Sun Yat-Sen University of Medical Sciences in China

Objectives To summarize the results of liver transplantation for various end-stage liver d iseases at the Sun Yat-Sen University of Medical Sciences (SUMS), define the ro le of liver transplantation in the treatment of hepatocellular carcinoma and ful minant hepatitis B, and assess the efficiency of lamivudine on preventing HBV re currence.Methods Seventy liver transplants performed at the SUMS between April 1993 and December 2000 were retrospectively analyzed. The main indications for liver transplant w ere hepatocellular carcinoma (26 cases), liver cirrhosis (21 cases), fulminant h epatitis B (12 cases), sclerosing cholangitis (4 cases) and other terminal liver diseases (7 cases). Lamivudine was used in twelve patients suffering from fulm inant hepatitis B. Logistic multivariate regression analysis was applied to det ermine the risk factors predicting liver transplantation outcomes.Results Fifty-four patients survived for more than one month, and 16 patients died with in 30 days after orthotopic liver transplantation (OLT). The overall hospital s urvival rate was 77.1%. The hospital survival rates in the Child’s A and B pat ients were 87.5% and 83.3%, respectively. Those rates were superior to those of the Child’s C patients (P&lt;0.05). The outcome of patients with small hep atocellular carcinoma (HCC) was superior to that of patients with large HCC. Pr eoperative APACE Ⅲ scores, the severity of ascites and serum creatine level had independent influence on outcome. Of the patients with fulminant HBV infection , 9 recipients survived for a follow-up period of 2-24 months. Treatment with lamivudine monotherapy was both well tolerated and efficacious in patients with fulminant hepatitis B.Conclusions The results indicate that orthotopic liver transplantation could provide long-t erm cure and palliation for patients with HCC, and that patient selection is ext remely important in predicting outcome. The results support the continued appli cation of liver transplantation as a therapeutic modality for various end-stage liver diseases and that lamivudine is an effective and safe monotherapy in OLT for patients with HBV infection.     

慢性重症乙型肝炎肝移植50例报告

目的:总结慢性重症乙型肝炎肝移植治疗的临床经验。方法:回顾分析了50例慢性重症乙型肝炎肝移植的临床资料及随访结果。结果:50例患者中术前肝功能状态全为Child C级;MELD指数平均为30;术前不同程度肝性脑病者占44%(22/50);术前腹腔感染占30%(15/50);术前肝肾综合征占40%(20/50);术前行人工肝支持治疗25例,共35例次;术前消化道出血8例,占16%;术前乙肝病毒活跃复制状态30例,占60%。全组围手术期死亡(术后30天内死手亡)6人,占12%;主要术后并发症按顺序排列如下:肺部感染25例占50%;多器官功能衰竭(MOF)10例,占20%,无原发性肝无功能,无血管系统并发症。围手术期(30天以内)生存率88%,一年生存率80%。用拉米呋啶加乙肝高价免疫球蛋白预防乙肝复发,平均随访12个月无一例乙肝复发。结论:慢性重症肝炎肝移植受体术前肝功能状态极差,多伴有全身各器官系统功能损害及内环境失调,术前应尽可能争取时间改善内环境和各器官系统功能,包括针对性地使用人工肝支持技术,术中注意凝血功能改善及尿量的维持,缩短手术时间;术后加强对肝、肺、肾功能的强化支持治疗,合理使用免疫抑制剂;有效预防和治疗肺部感染及二重感染。注意上述各个环节,慢性重症乙型肝炎肝移植治疗可获得满意的临床效果。     

Update on chronic viral hepatitis

Many recent and significant advances in the field of chronic viral hepatitis, including therapy, suggest that an update on chronic hepatitis is timely. Chronic hepatitis B virus infection remains a significant worldwide cause of liver cirrhosis and hepatocellular carcinoma, despite the wide availability of a long established and effective vaccine. Transmission occurs via perinatal, sexual, and parenteral routes (particularly intravenous drug abuse and although blood products still carry a risk, this is now extremely low in Western countries). Only a minority of infected adult cases develop chronic hepatitis but in children under 1 year, 90% develop chronic hepatitis. The clinical spectrum of chronic liver injury ranges from mild inflammation to end stage liver cirrhosis. Interferon alfa has been the mainstay of treatment for patients with active disease but nucleoside analogues (lamivudine and adefovir) are now available with similar efficacy. Patients with end stage liver disease and hepatocellular carcinoma can be offered transplantation but infection in the graft is commonplace. The combination of hepatitis B immunoglobulin and newer antiviral drugs reduce the incidence and severity of graft infection significantly. The hepatitis C virus epidemic of the latter half of the 20th century now affects more than 1% of populations worldwide. This RNA virus is spread parenterally and is becoming the leading indication for liver transplantation. The majority of patients develop chronic hepatitis, which may be progressive, evolving to significant liver disease (cirrhosis or hepatocellular carcinoma) in about 20% cases after decades. Treatment with the combination of interferon alfa and ribavirin is successful in up to 40% cases. Liver transplantation is a therapeutic option for some but graft infection is universal and often complicated by progressive liver fibrosis. A vaccine remains a remote prospect so that prevention is crucial. Hepatitis D virus infection occurs on a background of hepatitis B virus infection and can also cause liver damage. The response to antiviral therapy is poor. The newer "hepatitis" viruses G and TT do not cause significant liver injury.     

乙肝疫苗在肝移植后长期生存患者中的应用

目的为了评估乙肝疫苗预防乙肝相关疾病肝移植后乙肝复发的效果.方法肝移植后病人在拉米夫定和乙肝免疫球蛋白治疗24个月后,停用乙肝免疫球蛋白2个月,分别在第0,1,2,6个月时肌接种基因重组疫苗,每次20μg.接种第2,6个月时检测血清抗-HBs水平.如不能达到10 IU/L,再行一轮接种.结果接种后患者反应率为56%(5/9).结论结果表明乙肝预苗可以有效地诱导机体产生乙肝抗体,但其确切效果尚需进一步研究证实.     

Efficacy of hepatitis B immunoglobulin in relation to the gene polymorphisms of human leukocyte Fcγ receptor III (CD16) in Chinese liver transplant patients

Background Although the use of hepatitis B immunoglobulin (HBIG) may lead to a significant reduction in recurrent hepatitis B virus (HBV) infection and improve the survival of patients who have undergone liver transplantation (LT) for hepatitis B-related diseases, the recurrence of the disease still remains at a lower level. Different clinical curative effects were observed in patients with the same HBV-related diseases and the same therapy. This study was undertaken to investigate whether the efficacy of HBIG is associated with FCGR3A gene polymorphisms in Chinese liver transplant patients.Methods Altogether 77 patients who had received liver transplantation for hepatitis B-related diseases with more than one-year survival after surgery were studied. The recurrence of HBV was characterized by the appearance of HBsAg in serum after the operation. The FCGR3A genotyping was performed using genomic DNA sequencing (ABI 3037). Single nucleotide polymorphism at nucleotide 559 was detected by Polyphred. Results Of the 77 patients, 14 were complicated with HBV recurrence post-transplant. The FCGR3A at nucleotide 559 TT was observed in 35 (45.5％) subjects, whereas TG in 31(40.3％) and GG in 11(14.3％). In the 559G carrier group (n=42, 54.5%), the risk of HBV recurrence was 9.5%, and 1- and 2-year recurrence-free survival rates were 95.2% and 88.7%, respectively. In the 559G noncarrier group (n=35, 45.5%), the risk of HBV recurrence was 28.6%, and 1- and 2-year recurrence-free survival rates were 74.3% and 69.3%, respectively. The risk of HBV recurrence and the recurrence-free survival rate were both statistically different between the 559G carrier and noncarrier groups (P&lt;0.05).Conclusions A single nucleotide polymorphism（T/G）at position 559 of the FCGR3A gene was found in Chinese patients. The efficacy of HBIG in prophylaxis of HBV recurrence after LT is associated with the gene polymorphism, so detecting FCGR3A genotypes can be a clinical reference of the HBIG administration.     

YMDD变异受体肝移植术后乙型肝炎病毒再感染的预防

目的 探讨YMDD变异受体肝移植术后乙型肝炎病毒(HBV)再感染的预防方法.方法 2004年3月～2006年5月本中心20例术前合并YMDD变异的肝移植受体给予口服阿德福韦酯(ADV)联合肌肉注射乙肝免疫球蛋白(HBIG)作为预防方案,持续监测术前及术后的移植肝功能、血清HBV标志物、HBV-DNA定量、血肌酐等.结果 患者术后平均随访33.5个月,除1例死于肝癌复发外,其余患者均存活.术前HBV-DNA≥106copies/m1患者YMDD变异率为12.4%,HBV-DNA<106copies/ml患者为2.5%,两组间差异有统计学意义(P<0.05).95.0%(19/20)的患者于肝移植术后4周内HBV-DNA转阴性,5.0%(1/20)于术后6个月转阴性.此后长期复查HBsAg、HBeAg、HBV-DNA均阴性.所有患者均未出现HBV再感染.1例患者在服用ADV 1年后出现血肌酐水平持续增高.结论 应用ADV可有效预防YMDD变异受体肝移植术后HBV再感染.ADV有较低的肾毒性,用药期间仍需定期监测肾功能.     

不同程度慢性乙型肝炎患者肾脏移植术后的转归

目的：前瞻性随访观察慢性肾衰尿毒症合并不同程度的慢性乙型病毒性肝炎的患者，接受肾脏移植术后肝病转归情况。方法：开放性收集2000年8月至2002年2月39例肾脏移植患者，其中19例合并慢性乙型病毒性肝炎患者经皮肝活检组织病理学诊断，分为轻度（A组，n=8）、中度（B组，n=6）、重度（C组，n=5）肝炎3组，无肝炎组（D组，n=20），随访观察3年，术后定期观察血肌酐（Scr），肝功能相关指标（ALT，GGT，TB，CB，PT，A，G），环孢霉素A（CsA）谷值，乙肝病毒学相关指标、肝纤维化指标，肝脏B超，Child-Pugh评分变化，3组中各有2例进行重复肝活检组织病理学检查。结果：A组在随访3年中各项观察指标均无明显变化。B组从术后6个月开始GGT明显高于正常水平，在随访终点时Child-Pugh评分2例升至B级，2例重复肝活检显示已处于重度病变。C组从术后6个月开始GGT持续高于正常水平，24个月开始，血清白蛋白低于正常值，球蛋白高于正常值，随访终点时，Child-Pugh评分均在B级以上，有4例呈肝硬化改变，1例发现原发性肝癌改变，存活率仅为40％。结论：不同程度的慢性乙型病毒性肝炎患者肾脏移植术后预后有一定差别，肝脏组织病理学分组具有指导手术选择的意义。