肝移植围手术期HBV再感染的预防

目的探讨乙型肝炎病毒(HBV)相关疾病患者肝移植围手术期HBV再感染的预防措施。方法回顾近年相关文献并进行综述。结果对患HBV相关的急、慢性肝病的肝移植患者,预防移植后HBV再感染至关重要。目前不仅有多种预防HBV再感染的药物应用于临床,而且针对患者不同特点,在预防方案方面也有新的研究进展。结论肝移植是治疗HBV相关疾病的有效方法,围手术期合理准确地选择预防HBV再感染方案对延长患者肝移植术后存活期有重要意义。     

肝脏移植术后乙肝复发的防治进展

肝移植是治疗乙肝相关疾病的有效方法,但如何防治肝移植后乙型肝炎的复发,成为目前急需解决的问题。与HBV有关的急、慢性肝病是肝移植的主要适应证,围手术期的积极药物治疗,对提高乙肝相关疾病患者肝移植的成功率至关重要。     

预防肝移植后乙型肝炎复发的治疗现状

由于缺乏有效防止移植肝脏再感染HBV的方法，HBV相关的肝脏疾病一度被认为是肝移植（OLT）的手术禁忌症。上世纪90年代．随着乙肝免疫球蛋白（HBIG）以及拉夫米啶（LAM）的广泛应用HBV相关肝脏疾病的患者接受OLT术后的效果有了显著提高。     

肝移植术后乙肝复发的预防和治疗

乙型肝炎病毒(HBV)感染是亚洲良性终末期肝病的主要病因,欧美接受肝移植的患者中亦有5%~10%携带HBV。自1967年Starzl成功实施首例肝移植术,肝移植已成为治疗终末期肝病的有效方法,HBV相关急、慢性肝病逐渐成为肝移植的主要适应证,移植术后乙肝复发一直是影响移植肝存活和患者生存率的重要因素。近年来,乙肝免疫球蛋白(HBIg)、抗病毒药物等有效预防措施的应用,使HBV相关患者移植后疗效与HBsAg阴性患者相似甚至更好。研究表明,肝移植术后乙肝复发与以下因素有关:①术后大量免疫抑制剂的应用;②循环系统和/或肝外组织的HBV病毒颗粒感…     

肝移植术后预防乙型肝炎病毒再感染281例的分析

目的 分析乙型肝炎病毒（HBV）相关性肝病肝移植术后HBV再感染的原因及防治经验。方法 回顾性分析281例HBV相关性肝病，移植前后给予抗病毒药物拉米夫定＋人乙肝免疫球蛋白（HBIg）预防HBV再感染，其中9例为拉米夫定＋阿德夫韦＋HBIg，观察临床表现、血清HBV标志物、HBV DNA及肝活检免疫组织化学检测等指标。结果 用拉米夫定＋HBIg预防的272例中，有7例再感染，血清HBsAg、HBeAb和HBcAb阳性，肝活检免疫组织化学检测有HBsAg表达，其中2例血清HBV DNA阳性，4例经治疗后HBsAg又转阴。用拉米夫定＋阿德夫韦＋HBIg预防的9例中，血清学和肝活检免疫组织化学检测无HBsAg表达。结论 拉米夫定＋HBlg或拉米夫定＋阿德夫韦＋HBIg联合应用，可以有效预防HBV相关性肝病肝移植后HBV的再感染。     

肝移植术后肝癌复发对HBV再感染的影响

目的 探讨肝移植术后肝癌复发对HBV再感染的影响.方法 回顾性分析285例原发病为乙肝相关性疾病且术后随访超过半年的原位肝移植患者资料.结果 285例肝移植患者随访时间为6～59个月,术后HBV再感染10例,再感染率为3.5%.其中9例患者合并肝癌复发,HBV再感染发生于肝癌复发后1～7个月.肝癌复发患者与肝癌未复发和良性肝病患者HBV再感染的差异具有统计学意义.13例肝癌复发或转移灶切除标本中有1例免疫组化染色HBsAg阳性、HBcAg弱阳性.结论 乙肝免疫球蛋白联合核苷类似物是预防肝移植术后乙肝复发的有效治疗措施,肝癌复发是肝移植术后HBV再感染的重要原因.     

肝移植术后预防乙型肝炎病毒再感染281例的分析

目的分析乙型肝炎病毒(HBV)相关性肝病肝移植术后HBV再感染的原因及防治经验。方法回顾性分析281例HBV相关性肝病,移植前后给予抗病毒药物拉米夫定 人乙肝免疫球蛋白(HBIg)预防HBV再感染,其中9例为拉米夫定 阿德夫韦 HBIg,观察临床表现、血清HBV标志物、HBV DNA及肝活检免疫组织化学检测等指标。结果用拉米夫定 HBIg预防的272例中,有7例再感染,血清HBsAg、HBeAb和HBcAb阳性,肝活检免疫组织化学检测有HBsAg表达,其中2例血清HBV DNA阳性,4例经治疗后HBsAg又转阴。用拉米夫定 阿德夫韦 HBIg预防的9例中,血清学和肝活检免疫组织化学检测无HBsAg表达。结论拉米夫定 HBIg或拉米夫定 阿德夫韦 HBIg联合应用,可以有效预防HBV相关性肝病肝移植后HBV的再感染。     

肝移植术后HBV再感染的治疗

目的分析肝移植术后乙型肝炎病毒（HBV）再感染患者的抗病毒治疗与乙肝病毒基因变异情况。方法317例HBV相关终末期肝病患者肝移植术后15例单独使用LAM，302例使用小剂量乙肝免疫球蛋白（hepatitis B immune globulin，HBIG）和拉米夫定（lamivudine，LAM）（或adefovir dipivoxil，ADV）联合预防HBV再感染，同时检测HBV血清标志物、血清HBV DNA、YMDD区变异、及肝活检组织乙型肝炎标记物。结果术后LAM组有4例术前HBV DNA阳性患者术后HBV再感染，LAM＋HBIG联合用药组16例HBV再感染，两组术后HBV再感染差异有统计学意义（26．7％VS．5．30％，P〈0．01）。317例患者术后12例发生YMDD变异，发生率为3．79％，再感染病例60％（12／20）。经加用ADV治疗后5例HBV DNA转阴性，4名患者HBV DNA滴度下降，肝功能显著改善，3例发生纤维淤胆性肝炎，2例死亡，1例经再次肝移植治愈。结论小剂量HBIG＋LAM可以有效地预防肝移植术后HBV再感染；在小剂量HBIG＋LAM用药基础上HBV再感染可能产生YMDD（tyrosine，methionine，aspartate，aspartate）变异；ADV可作为LAM耐药后用药，对于发生突破性感染的患者应采取以ADV为主的综合治疗。     

拉米夫定联合小剂量乙肝免疫球蛋白预防肝移植术后HBV再感染的临床分析

目的探讨拉米夫定联合小剂量乙肝免疫球蛋白预防肝移植术后HBV再感染的效果。方法回顾性分析76例HBV相关性肝病患者肝移植术后采用拉米夫定联合小剂量乙肝免疫球蛋白预防HBV再感染的临床资料,分析HBV再感染的危险因素。结果 76例患者术后HBs Ag转为阴性,HBV再感染9例,术后1年内HBV再感染率为9.2%(7/76),2年内再感染率11.8%(9/76)。结论拉米夫定与小剂量乙肝免疫球蛋白联合应用可有效地预防肝移植术后HBV的再感染,肝移植术前HBe Ag阳性及HBV-DNA阳性是HBV再感染的危险因素。     

肌注型HBIg预防肝移植术后乙肝病毒再感染的疗效分析

目的评价小剂量肌肉注射剂型乙肝免疫球蛋白（HBIg）联合核苷类抗病毒药物预防肝移植术后乙肝病毒（HBV）再感染的疗效。方法对2003年9月至2004年12月在中山大学附属第三医院肝移植中心施行肝移植术且符合研究标准的130例病人进行前瞻性研究。采用肌肉注射剂型HBIg联合核苷类抗病毒药物预防术后乙肝病毒再感染，术后监测HBV再感染情况并同国内外研究进行比较。结果130例中128例术后血清HBsAg转为阴性并检测到HBsAb，平均随访12．2个月，HBV再感染率为6.3％（8／128）；对照组再感染率为3．1％，两组比较差异无显著性（P〉0．05）。结论肌注型HBIg联合核苷类抗病毒药物能有效预防肝移植术后HBV再感染。     

Viral load at the time of liver transplantation and risk of hepatitis B virus recurrence.

Hepatitis B virus (HBV) recurrence after liver transplantation is significantly reduced by prophylaxis with hepatitis B immune globulins (HBIG) or antiviral drugs in nonreplicating patients and by the combination of both drugs in replicating patients. However, the load of HBV DNA, which defines replicating status in patients undergoing liver transplantation, remains unclear. This study analyzes the correlation between the viral load, tested with a single amplified assay, at the time of liver transplantation, and the risk of hepatitis B recurrence in 177 HBV carriers who underwent transplantation in a single center from 1990 to 2002. Overall, HBV relapsed after surgery in 15 patients (8.5%) with a 5- and 8-year actuarial rate of recurrence of 8% and 21%, respectively. After liver transplantation hepatitis B recurred in 9% of 98 selected subjects treated only with immune globulins and in 8% of 79 viremic patients who received immune globulins and lamivudine (P = NS). A linear correlation was observed between recurrence and viral load at the time of surgery. In transplant patients with HBV DNA higher than 100,000 copies/mL, 200-99,999 copies/mL, and DNA undetectable by amplified assay, hepatitis B recurred in 50%, 7.5%, and 0% of patients, respectively. Overall, a viral load higher than 100,000 copies/mL at the time of liver transplantation was significantly associated with hepatitis B recurrence (P = .0003). In conclusion, spontaneous or antiviral-induced HBV DNA viral load at the time of surgery classifies the risk of HBV recurrence after liver transplantation and indicates the best prophylaxis strategy.     

受体相关肝移植术后乙肝复发的危险因素分析

目的 本研究旨在探讨影响受体相关肝移植术后乙肝复发的危险因素.方法 回顾性搜集、随访、分析北京朝阳医院2013—2019年7年中连续320例有乙肝病史并行肝移植手术治疗的患者的临床资料,搜集可能与乙肝复发有关的围术期参数,并对可能影响患者术后乙肝复发的危险因素进行分析.结果 在320例患者中,原发疾病为乙肝所致肝恶性肿...     

拉米夫定联合小剂量乙型肝炎免疫球蛋白预防肝移植术后乙型肝炎病毒复发

目的:初步探讨拉米夫定联合小剂量乙型肝炎免疫球蛋白预防肝移植术后乙型肝炎病毒(HBV)复发的疗效。方法:35例HBV相关疾病病人接受肝移植后使用拉米夫定联合小剂量乙型肝炎免疫球蛋白(HBIg)预防HBV复发,同时监测乙型肝炎血清标志物、血清HBV鄄DNA、YMDD区变异及肝活检组织乙型肝炎标记物免疫组化。结果:本组病例平均获随访557d,结果5例(14.3%)出现了HBV复发:复发病例中2例HBV鄄DNA阳性,无YMDD变异。病人术前HBeAg状态与肝移植术后HBV复发间无明显相关(P>0.05),而术前HBV鄄DNA阳性的病人术后HBV复发率显著增加(P<0.05)。结论:拉米夫啶联合小剂量HBIg预防肝移植术后HBV复发的近期疗效较为肯定。术前HBV鄄DNA状态是影响术后HBV复发的重要因素。     

小剂量HBIg联合核苷类似物预防肝移植术后乙肝复发1506例回顾性分析

目的 确定小剂量乙肝免疫球蛋白(HBIg)联合核苷类似物预防肝移植术后乙肝复发的效果.方法 对我院1998年12月至2009年11月间因乙肝相关性终末期肝病行肝移植手术并接受核苷类似物联合小剂量HBIg预防乙肝复发病例进行回顾性分析,调查其术前、术后乙肝相关检查、乙肝复发情况以及患者的生存情况.结果 在移植术后存活>30 d且获得随访(中位随访时间为27.8个月)的1506例患者中,术后出现乙肝复发者37例.术后1、2、3、4、5、6年累计复发率分别为1.3%、2.4%、2.7%、2.9%、3.7%、4.6%;术后乙肝复发时间为0.3～66.6个月(中位值为12.8个月).在37例乙肝复发患者中,9例检测出病毒变异,其中YMDD变异4例,YMDD+YIDD变异2例,YMDD+YVDD变异、YVDD变异、YIDD变异各1例.结论 肝脏移植为治疗乙肝相关性肝病的重要手段,术后采用核苷类似物联合小剂量HBIg可有效预防乙肝复发,乙肝复发患者及时采取挽救治疗可控制疾病,改善预后.

Abstract：

Objective To evaluate the preventive effect of combination of low-dose HBIg and Nucleoside analogues on recurrence of hepatitis B after liver transplantation. Methods Retrospectively analyzed HBV status and recurrence in patients accepting Nucleoside analogues plus low-dose HBIg as prophylaxis treatment after liver transplantation for HBV-related end-stage liver disease from December 1998 to Octomber 2009 in our center. Results In all the 1506 patients whose survival time >30 d after liver transplantation, 37 patients showed HBV recurrence, the HBV cumulative-recurrence rate of 1, 2, 3, 4, 5 and 6y was 1.3%,2. 4%,2. 7%,2. 9%,3. 7% and 4.6% respectively. The time of recurrence varied from 0. 3 to 66. 6 months (median 12. 8 months) after transplantation. Virus mutation could be tested in 9 cases of the 37 recurrence patients, including 4 YMDD cases, 2 YMDD + YIDD cases, 1 YMDD+YVDD cases, 1 YVDD case,and 1 YIDD case. Conclusions Liver transplantation is the principal therapeutic method for the patient with end-stage liver diseases related to HBV, with the effectively prophylaxis treatment to aim directly at HBV recurrence. If the patients who got HBV recurrence received targeted treatments, the situation can be controlled satisfactorily.     

肝移植术后预防乙型肝炎病毒再感染的策略

目的探讨预防肝移植术后乙型肝炎病毒（HBV）再感染的综合策略.方法对术前存在HBV感染的130例肝移植患者进行前瞻性研究,采用肌肉注射剂型乙型肝炎免疫球蛋白（IMHBIg）联合口服拉米夫定（lamivudine）作为预防术后HBV再感染的治疗方案;术后监测HBV再感染的情况.结果在130例患者中,128例术后HBsAg转为阴性,检测血清HBsAb呈阳性.平均随访12.2个月,8例出现HBV再感染,再感染率为6.3%;术前HBeAg阳性者再感染率为14.3%,阴性者4.0%,两组间差异有统计学意义（P＜0.05）;术后第一天HBsAg阳性者再感染率为21.1%,阴性者3.7%,两组间差异有统计学意义（P＜0.05）.结论拉米夫定联合肌肉注射剂型的人乙型肝炎免疫球蛋白可有效预防肝移植术后HBV再感染;术前血清HBeAg阳性以及术后第一天HBsAg者是术后HBV复发的高危因素.     

Posttransplantation Hepatitis B Prophylaxis with Combination Oral Nucleoside and Nucleotide Analog Therapy

Liver transplant recipients are at risk of developing recurrent hepatitis B after liver transplantation for hepatitis B virus (HBV)‐related liver disease. We evaluated the efficacy of a new hepatitis B prophylaxis regimen involving conversion from at least 12 months of HBIg with lamivudine to combination therapy with an oral nucleoside and nucleotide analog. Between June 2008 and May 2010, a total of 61 liver transplant recipients were converted to a combination of a nucleoside and nucleotide analog. The mean (±standard deviation) follow‐up time after conversion was 15.0 (±6.1) months. Recurrent HBV occurred in two (3.3%) patients at 3.1 and 16.6 months after HBIg cessation. The overall person time incidence rate for HBV recurrence after HBIg cessation was 2.7 cases per 100 person‐years. The estimate of HBV recurrence was 1.7% at 1 year after HBIg cessation. HBIg cessation a minimum of 12 months after liver transplantation with subsequent combination therapy with a nucleoside and nucleotide analog provides effective prophylaxis against recurrent HBV infection. The clinical implications of HBsAg detection without clinical, biochemical or molecular manifestations of recurrent hepatitis B require further study.     

拉米夫定对肝移植术后乙肝病毒再感染的预防作用

目的 探讨单一应用拉米夫定预防良性乙肝相关性肝病肝移植术后乙肝病毒再感染的疗效。方法 总结单一应用拉米夫定预防肝移植术后生存时间大于3个月的31例良性乙肝相关性终末期肝病患者的乙肝病毒再感染情况，同时检测肝移植手术前、后血清及肝穿刺组织乙肝表面标志物及HBVDNA的变化。结果 31例患者随访时间平均为38．2个月（3．2～70．2个月），随访期间死亡8例。乙肝病毒总的再感染率为19．4％（6／31），术后1、3、5年乙肝再感染率分别为7．1％（2／28）、16．0％（4／25）及26．1％（6／23），生存率分别为87．1％（27／31）、80．6％（25／31）及66．1％（20．5／31）。术前HBeAg和HBVDNA的清除率分别为54．5％（6／11）和50．0％（5／10）。术前HBVDNA和HBeAg阳性患者术后乙肝病毒再感染率高。结论 拉米夫定可以有效地预防良性乙肝相关性肝病患者肝移植术后乙肝病毒的再感染；术前应尽可能使HBVDNA和HBeAg转阴。     

Left Lobe Auxiliary Liver Transplantation for End‐stage Hepatitis B Liver Cirrhosis

Auxiliary liver transplantation (ALT) for hepatitis B virus (HBV)‐related liver cirrhosis previously showed poor results, because the native liver was a significant source of HBV recurrence and the graft could be rapidly destroyed by HBV infection in an immunosuppressive condition. Four patients with HBV‐related liver cirrhosis were unable to undergo orthotopic liver transplantation because the only available grafts of left lobe were too small. Under entecavir‐based anti‐HBV treatment, they underwent ALT in which the recipient left liver was removed and the small left lobe graft was implanted in the corresponding space. The mean graft weight/recipient weight was 0.49% (range, 0.38%–0.55%). One year after transplantation, the graft sizes were increased to 273% and the remnant livers were decreased to 44%. Serum HBV DNA was persistently undetectable. Periodic graft biopsy showed no signs of tissue injury and negative immunostaining for hepatitis B surface antigen and hepatitis B core antigen. After a mean follow‐up period of 21 months, all patients live well with normal graft function. Our study suggests that ALT for HBV‐related liver cirrhosis is feasible under entecavir‐based anti‐HBV treatment. Successful application of small left livers in end‐stage liver cirrhosis may significantly increase the pool of left liver grafts for adult patients.     

Lamivudine for hepatitis B in liver transplantation: a single-center experience

BACKGROUND: Liver transplantation for hepatitis B virus (HBV) has been associated with a high rate of reinfection and graft failure. Lamivudine, a potent inhibitor of HBV replication, has been shown to prevent viral recurrence after transplantation. METHODS: The effectiveness of lamivudine monotherapy for the management of HBV recurrence after liver transplantation was assessed. Lamivudine was used in three patient groups: (1) patients started before transplantation and continued after transplantation (n = 13); (2) patients treated after transplantation (n = 15); and (3) patients with de novo hepatitis B after transplantation (n = 4). RESULTS: Median follow-up on lamivudine was 24 months. Active viral replication (HBV-DNA+) was seen in 17 (53%) of 32 at treatment initiation. All lost HBV-DNA at a mean of 2.4+/-1.6 months after lamivudine initiation. Twenty-six (81%) patients remain free of viral recurrence. Six (19%) patients have evidence of breakthrough infection with the YMDD mutant of HBV, two of whom progressed to graft failure. All four patients in group 1 who developed breakthrough had evidence of hepatitis B surface antigen expression in the explanted liver by immunohistochemistry despite being serum HBV-DNA negative before transplantation. No difference was observed among the three groups in DNA clearance or breakthrough rates. CONCLUSIONS: Lamivudine achieves viral DNA clearance in almost all patients. Expression of viral antigens in the liver seems to identify patients at risk of developing HBV-DNA recurrence. Disease-free survival of 81% at 22 months is similar to data with hepatitis B immunoglobulin therapy. Given the safe clinical profile and high efficacy in the prevention of disease recurrence, lamivudine will favorably change the outlook of liver transplantation for HBV.