预防肝移植患者慢性乙型肝炎复发抗病毒治疗现状及进展

在中国,因乙型肝炎病毒(HBV)感染相关终末期肝病或者肝癌而行肝移植治疗的病例居于肝移植首位。乙型肝炎免疫球蛋白(HBIG)和口服抗HBV药物的上市及抗病毒治疗的不断发展,显著改善了HBV相关肝移植患者的预后。在肝移植术前进行积极的抗病毒治疗可显著降低术后HBV的复发。所有出现HBV相关终末期肝病或原发性肝癌(HCC)等待肝移植的HBsAg阳性患者,在移植前均应接受强效、有高耐药基因屏障的核苷(酸)类药物(NAs)治疗,在移植前达到尽可能低的血清HBV DNA水平。肝移植术中属于无肝期,加用HBIG可以取得更好的效果。术后需HBIG和NAs联合用药以预防HBV复发。术后抗HBV复发常需终身治疗,长期联合应用强效高耐药基因屏障核苷(酸)类似物和小剂量HBIG后,可逐渐停用HBIG,并最好以强效与高基因耐药屏障药物口服NAs药物单药治疗,已成为目前术后预防HBV复发的重要推荐方案。     

肝移植术后乙型肝炎复发患者的预后分析

目的 分析肝移植术后乙型肝炎复发患者的预后及其相关资料.方法 回顾性分析天津市第一中心医院器官移植中心1998年12月至2009年11月因乙型肝炎相关终末期肝病行肝移植术,且术后接受小剂量乙型肝炎免疫球蛋白联合核苷(酸)类似物预防乙型肝炎复发的1506例患者资料.对其中出现复发病例的资料及其预后进行分析.所有患者术后均行HBV相关血液学检测,检测HBV DNA水平、肝功能,HBV血液学标志物阳性时行肝脏病理学活组织检查,随访至2010年11月.生存分析及复发率采用Kaplan-Meier生存分析,复发率及生存率的比较采用log-rank test检验.结果 共有38例肝移植术后病例确诊为乙型肝炎复发,中位随访时间为45.1个月,非肝癌肝移植患者乙型肝炎中位复发时间为31.8个月(0.3 ～ 72.8个月),肝癌肝移植患者乙型肝炎中位复发时间为13.7个月(0.3 ～ 66.6个月);8例患者检测出HBV耐药基因变异;18例病例接受恩替卡韦或阿德福韦酯挽救治疗,病毒复制转为阴性,肝功能恢复正常;其中22例病例由于肝癌复发、肝功能衰竭及其他原因死亡,16例病例生存.结论 HBV耐药基因变异及肝癌复发是肝移植术后乙型肝炎复发的重要原因,良性肝病肝移植患者乙型肝炎复发后接受阿德福韦酯或恩替卡韦挽救治疗可获得较好预后,而肝癌肝移植术后乙型肝炎复发患者预后较差.     

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复发

目的比较单用拉米夫定和拉米夫定联合个体化小剂量肌肉注射乙型肝炎免疫球蛋白两种方案,预防乙型肝炎相关良性终末期肝病患者肝移植术后乙型肝炎复发的疗效。方法111例因乙型肝炎相关良性终末期肝病患者在肝移植术前根据乙型肝炎免疫球蛋白的可获得性非随机分为单用组和联用组,单用组32例患者在移植术后接受拉米夫定100mg/d单药治疗,联用组79例患者在移植术后接受拉米夫定100mg/d和个体化小剂量肌肉注射乙型肝炎免疫球蛋白(维持血清抗- HBs滴度>100U/L)联合治疗。研究总体中位随访时间为32(1～88)个月,监测患者HBsAg、HBV DNA、抗-HBs和YMDD变异情况,随访患者生存率及乙型肝炎复发率。结果单用组共有5例患者乙型肝炎复发,其中3例发生HBV YMDD变异;肝移植术后1、2、3年累积乙型肝炎复发率分别为7.1%、14.3%、17.9%,患者生存率分别为87.5%、84.4%、74.6%。联合组共有2例患者乙型肝炎复发,且均发生YMDD变异;肝移植术后1、2、3年累积乙型肝炎复发率分别为0、1.8%、5.7%,患者生存率分别为83.5%、80.9%、77.6%。两组患者乙型肝炎复发率之间差异有统计学意义(P<0.05),单用组肝移植术前HBV DNA活跃复制与肝移植术后乙型肝炎复发相关(P<0.05),而联用组两者之间无相关性(P>0.05)。结论个体化小剂量肌肉注射乙型肝炎免疫球蛋白联合拉米夫定与单用拉米夫定相比,能更有效地降低良性终末期乙型肝炎患者肝移植术后乙型肝炎复发的风险。     

HBV感染患者经核苷(酸)类似物抗病毒治疗后病毒血症的临床分析

目的:观察HBV感染相关慢性肝病患者经核苷(酸)类似物抗病毒治疗后HBV DNA载量的分布情况,并探讨病毒血症的临床特点及意义。方法:采用COBAS^? TaqMan 48系统核酸定量仪对服用核苷(酸)类似物抗病毒治疗至少1年的541例患者的HBV DNA进行检测,分析经核苷(酸)类似物治疗后病毒血症分布情况。结果:在541例患者中,有153例(28.28%)检出HBV DNA,其中HBV DNA≥2000 IU/mL有31例(5.73%),低病毒血症(LLV)有122例(22.55%)。慢性乙型肝炎、肝硬化、肝癌患者LLV检出率分别为14.29%、17.00%、33.51%,差异有统计学意义(P<0.05)。LLV组患者HBsAg、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平显著高于HBV DNA<20 IU/ml组,低于HBV DNA≥2000 IU/ml组(P<0.05);LLV组患者肝硬度值(LSM)显著高于HBV DNA<20 IU/ml组(P<0.05),与HBV DNA≥2000 IU/ml组组间差异无统计学意义(P>0.05)。结论:HBV感染相关慢性肝病患者经核苷(酸)类似物抗病毒治疗后仍有一部分患者采用高灵敏度检测方法可以检出病毒标志物,其中大部分为低病毒血症,病毒血症与肝脏持续活动性炎症、肝纤维化进展及肝癌的发生密切相关。     

肝移植后病毒性肝炎的复发及肝炎病毒再感染

肝移植是目前治疗终末期肝病的有效方法,在我国,病毒性肝炎相关性肝病是接受肝移植患者的主要病因.随着经验的积累,肝移植就手术过程而言已有相当高的成功率,影响术后生存率的主要因素有术后感染、慢性排斥及胆道梗阻、移植后肝炎复发等.众多的研究结果表明,乙型肝炎免疫球蛋白(hepatitis Bimmunoglobulin,HBIG)联合核苷(酸)类似物能显著降低肝移植术后HBV再感染率及肝炎复发率,但该方案仍存在HBIG费用昂贵、使用不便及部分抗HBV药物耐药率高等问题.对于丙型肝炎,目前仍没有特效的预防方案可以很好地预防术后再感染及复发,在移植前用干扰素联合利巴韦林进行抗病毒治疗降低病毒载量可以减少术后复发的机会和严重程度,但由于药物的不良反应、移植术前患者的肝功能状态以及移植时间的不确定性,很难在术前常规对丙型肝炎患者进行抗病毒治疗.     

不同风险人群肝移植术后预防乙型肝炎复发治疗17年的疗效研究

目的观察不同风险人群在肝移植术后乙型肝炎的复发情况, 为以后是否早期停用乙型肝炎免疫球蛋白(HBIG)提供有用信息。方法根据肝移植术后乙型肝炎复发防治指南分为高、低风险人群及特殊人群[尤其原发性肝细胞癌(HCC)], 观察这部分人群乙型肝炎复发情况及复发的危险因素。计量资料组间比较采用t检验、秩和检验;计数资料组间比较采用χ2检验。结果最终纳入532例乙型肝炎相关肝移植患者。肝移植术后共35例出现HBV复发, 其中HBsAg阳性34例, HBsAg阴性1例, 乙型肝炎病毒(HBV) DNA阳性10例。乙型肝炎总的复发率为6.6%。术前HBV DNA阳性的高风险人群乙型肝炎的复发率为9.2%, HBV DNA阴性低风险人群的复发率为4.8% (P = 0.057)。肝移植术前诊断为HCC的293例患者中术后30例出现乙型肝炎复发, 复发率为10.2%。HCC患者肝移植术后乙型肝炎复发的独立相关因素为HCC复发(HR = 181.92, 95%CI 15.99～2 069.96,P < 0.001)、术后吗替麦考酚酯分散片(MMF)剂量高(HR = 5.190, 95%CI 1.28...     

非乙型肝炎相关性肝移植术后新发乙型肝炎病毒感染的9年队列研究

目的了解非乙型肝炎相关性肝移植术后患者新发HBV感染的发生率、危险因素、临床特点及转归。方法随访单中心非乙型肝炎相关性肝移植术后患者97例,在肝移植术前及术后随访期间规律记录患者的肝功能、乙型肝炎病毒标志物、HBV DNA定量及相关用药等情况。结果 97例患者的供体均HBsAg阴性,平均随访54个月(6~112个月),15例出现HBsAg阳性(15.46%),受体抗-HBc阴性是术后新发乙型肝炎的危险因素(RR=4.62),抗-HBs/抗-HBc双阳性是术后新发乙型肝炎的保护因素(RR=5.16),而低水平抗-HBs阳性并不能防止术后新发乙型肝炎(RR=1.32)。15例新发乙型肝炎时间为肝移植术后2~47个月(中位时间8个月),13例(86.67%)同时出现HBV DNA阳性,7例(46.67%)出现生物化学异常(均为HBV DNA阳性)。经核苷类似物治疗11例(73.33%)发生HBsAg血清学转换,但1例停药后HBsAg复阳,5例持续HBsAg阳性,慢性化率为33.33%,高于非移植人群。结论非乙型肝炎相关性肝移植术后存在新发乙型肝炎的风险,慢性化率高于非移植人群,应规范预防措施。     

不同用法的乙型肝炎免疫球蛋白对肝移植患者术后复发的预防作用

目的:评价乙型肝炎免疫球蛋白(HBIg)不同用法联和拉米夫定(LAM)对乙型肝炎相关性终末期肝病患者行原位肝移植术(OLT)后复发的预防作用.方法:2003-07/2008-02行同种异体肝移植患者89例,根据HBIg用法的不同分为2组:试验组43例,静点HBIg联合LAM; 对照组46例,肌肉注射HBIg联合LAM.分析患者乙型肝炎患者再感染率和复发率.结果:试验组2例再感染,再感染率4.65%,1例证实有乙型肝炎复发,复发率为2.33%; 对照组4例再感染,再感染率8.69%,3例证实有乙型肝炎复发,复发率为6.52%; 2组中再感染及复发病例均发生在术前1 wk内HBV DNA阳性的患者中,两者相比有显著统计学差异( P<0.05).结论:LAM联合静点HBIg可以有效降低HBVDNA阳性患者OLT后乙型肝炎复发率.     

肝移植术后原发性肝癌复发与乙型肝炎病毒再感染的关系

目的 探讨肝移植术后原发性肝癌复发与HBV再感染的关系.方法 对2004年1月-2008年12月在中山大学附属第三医院因乙型肝炎相关性终末期肝病行肝移植手术并长期随访的340例患者回顾性分析.患者被列入肝移植等待名单后给予核苷(酸)类似物抗病毒治疗,术中和术后均给予核苷(酸)类似物联合低剂量乙型肝炎免疫球蛋白进行预防.术后定期随访并监测患者HBV再感染的发生率及生存率,用多因素COX回归分析筛选出影响术后HBV再感染的危险因素.计量资料用t检验、计数资料用x2检验进行统计学处理.用Kaplan-Meier方法进行生存率分析,对HBV再感染危险因素用COX多因素回归分析,对HBV再感染与原发性肝癌复发的时间进行Spearman线性相关分析.结果 340例患者术后发生HBV再感染33例,术后1、3、5年再感染率分别为7%、10%、13%.HBV再感染的时间为1～21个月,中位数为5个月.原发病为原发性肝癌(风险比为2.98;95%可信区间为1.08～8.25,P＜0.05)、术前HBV DNA载量＞5log10拷贝/ml(风险比为3.99;95%可信区间为1.85～8.62,P＜0.01)是发生HBV再感染的危险因素.原发性肝癌复发者HBV再感染发生率高于未复发者,分别为27.9%和8.7%(风险比为4.58; 95%可信区间为1.88～11.12;P＜0.01).12例患者肝移植术后发生HBV再感染和原发性肝癌复发,两者的复发时间具有相关性(r=0.583,P＜0.05).结论肝移植术后原发性肝癌复发是HBV再感染的危险因素.

Abstract：

Objective To investigate the relationship between hepatocellular carcinoma (HCC)recurrence and hepatitis B virus (HBV) recurrence. Method The clinical data of 340 patients underwent liver transplantation due to HBV related end-stage liver disease and received long-term follow up in our hospital from Jan 2004 to Dec 2008 were retrospectively analyzed. All patients received nucleoside analogues therapy formally before entering into the waiting list and nucleoside analogues combined low-dose HBIG therapy during and after transplantation. Patients were regularly followed up at the outpatient, monitoring the HBV recurrence and survival. Multivariate Cox regression analysis was used to evaluate the risk factors for hepatitis recurrence. Result 33 patients suffered from HBV recurrence post transplantation.The 1-, 3- and 5- year recurrence rates were 7.0%, 10% and 13% respectively. The median HBV recurrence time was 5 months (1-21 months). COX regression analysis revealed that risk factors for HBV recurrence were HCC (HR = 2.98; 95% CI 1.08-8.25; P＜0.05) and pre-transplantation HBV-DNA load over 5 log10 copies/ml (HR = 3.99; 95% CI 1.85-8.62; P＜0.01). Further stratified analysis showed that patients who suffered from carcinoma recurrence had a higher incidence of HBV recurrence than those who did not, which were 27.9% and 8.7% (HR =- 4.58;95% CI 1.88-11.12; P＜0.01) respectively. 12 patients suffered from both HCC and HBV recurrence. Spearman correlation analysis demonstrated a strong correlation between HBV and HCC recurrence times (r= 0.583, P＜0.05). Conclusion Post transplantation HCC recurrence is a risk factor for HBV recurrence.     

肝移植术后乙型肝炎复发的防治经验

近年来随着新一代核苷类似物如拉米夫定的应用、免疫抑制方案的改进，在预防肝移植术后乙型肝炎复发方面取得了良好的效果。我院1999年1月至今实施肝移植88例，其中70例为乙型肝炎病毒(HBV)相关肝病。现将预防乙型肝炎复发的经验报道如下。     

乙型肝炎相关性肝移植后乙型肝炎复发的临床特点分析

目的 总结和探讨乙型肝炎相关性终末期肝病患者在肝移植术后乙型肝炎复发的临床特点.方法 回顾性分析2005年4月至2010年4月期间的253例乙型肝炎相关性肝移植患者的术后随访资料.结果 253例肝移植患者中乙型肝炎复发16例,复发率6.32%(16/253),中位复发时间为术后13个月,术后1、3、5年的累积复发率分别...     

Prophylactic managements of hepatitis B viral infection in liver transplantation

Liver transplantation (LT) is a considerably effective treatment for patients with end-stage hepatitis B virus (HBV)-related liver disease. However, HBV infection often recurs after LT without prophylaxis. Since the 1990s, the treatment for preventing HBV reinfection after LT has greatly progressed with the introduction of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues (NAs), resulting in improved patient survival. The combination therapy consisting of high-dose HBIG and lamivudine is highly efficacious for preventing the recurrence of HBV infection after LT and became the standard prophylaxis for HBV recurrence. However, mainly due to the high cost of HBIG treatment, an alternative protocol for reducing the dose and duration of HBIG has been evaluated. Currently, combination therapy using low-dose HBIG and NAs is considered as the most efficacious and cost-effective prophylaxis for post-LT HBV reinfection. Recently, NA monotherapy and withdrawal of HBIG from combination therapy, along with the development of new, potent high genetic barrier NAs, have provided promising efficacy, especially for low-risk recipients. This review summarizes the prophylactic protocol and their efficacy including prophylaxis of de novo HBV infection from anti-HBc antibody-positive donors. In addition, challenging approaches such as discontinuation of all prophylaxis and active immunity through hepatitis B vaccination are discussed.     

Recent advances in prevention of hepatitis B recurrence after liver transplantation

Liver transplantation is the only effective treatment for hepatitis B virus(HBV)-related end-stage liver disease.However,without antiviral prophylaxis,the recurrence rate of hepatitis B is as high as 80%-100%,which leads to a 50% mortality rate in the first 2 years after liver transplantation.Combination therapy of hepatitis B immunoglobulin(HBIG) and lamivudine demonstrated a higher efficacy of prophylaxis and further reduced the rate of recurrence to < 10%.The strategy of HBIG combined with lamivudine has been the standard treatment in many centers.However,the high rate of lamivudine resistance and the many disadvantages of HBIG have compelled surgeons to reconsider the longterm efficacy of this strategy for the prevention of HBV reinfection.Recently,new nucleos(t)ide analogues,such as entecavir and tenofovir,have been approved as first-line monotherapies for the treatment of chronic hepatitis B infection.These antiviral medicines have replaced lamivudine as the first choice in the prevention of HBV recurrence after liver transplantation.Various therapies that are composed of entecavir,tenofovir,and lamivudine plus adefovir,with or without HBIG have been adopted in several liver transplant centers.This article reviews the recent advances in prophylaxis for the recurrence of hepatitis B after liver transplantation.     

Hepatitis B prophylaxis post liver transplantation with newer nucleos(t)ide analogues after hepatitis B immunoglobulin discontinuation

Newer nucleos(t)ide analogues (NUCs) have better resistance profiles making hepatitis B immunoglobulin (HBIG)‐sparing protocol an attractive prophylactic approach against hepatitis B virus (HBV) recurrence after liver transplantation (LT). We evaluated the risk of HBV recurrence after withdrawal of HBIG in patients who had been under HBIG plus NUCs after LT. Stable patients without HBV recurrence after LT while receiving combination of HBIG plus NUCs for at least 12 months were eligible for HBIG discontinuation. The patients were at low risk for HBV recurrence (only 4.5% had detectable HBV DNA at the time of LT, and 32% had HBV/hepatitis D virus co‐infection). All patients were followed up with HBV serum markers, HBV‐DNA, and evaluation of renal function, including glomerular filtration rate. Forty‐seven recipients discontinued HBIG and were maintained on newer NUCs. Median follow‐up post‐HBIG withdrawal was 24 months (range: 6–40 months). Twenty‐eight (60%) patients continued on lamivudine in combination with adefovir dipivoxil (n = 23, 82%) or tenofovir (n = 5, 18%); 10 (21%) and 9 (19%) of the 47 patients continued on tenofovir and entecavir monoprophylaxis, respectively. Although 3 (6.3%) patients developed detectable hepatitis B surface antigen, all of them had undetectable HBV DNA and no clinical manifestations of HBV recurrence. Renal function was similar between the different groups of patients. In conclusion, maintenance therapy with newer NUCs after discontinuation of HBIG prophylaxis was effective, but further studies in larger cohorts with longer follow‐up are needed.     

Lamivudine plus low-dose hepatitis B immunoglobulin to prevent recurrent hepatitis B following liver transplantation

BACKGROUND AND AIMS: High-dose intravenous hepatitis B immunoglobulin (HBIG) may prevent recurrent hepatitis B virus (HBV) infection, but the cost has limited its widespread use in countries with endemic HBV infection. We report on long-term safety and efficacy of an alternative strategy of very low doses (400-800 IU/month) of intramuscular (IM) HBIG plus lamivudine. METHODS: Australian and New Zealand patients who received low-dose HBIG plus lamivudine following liver transplantation for HBV-related end-stage liver disease were studied. Prior to transplantation, patients with detectable serum HBV DNA received lamivudine 100 mg daily. Posttransplantation, all patients received lamivudine 100 mg daily plus IM HBIG 400 or 800 IU daily for 1 week then monthly thereafter. Serum HBV DNA levels were measured prior to lamivudine, at transplantation, and at 12 months posttransplantation. Serum titers of antibody to HBV surface antigen were measured at 1, 3, and 12 months posttransplantation. RESULTS: Between February 1996 and October 2004, 147 patients received low-dose HBIG plus lamivudine. Thirty-one percent were hepatitis B e antigen positive, and 85% were HBV DNA+ prior to transplantation. The median duration of pretransplantation lamivudine was 92 days (range, 1-1775). Median follow-up posttransplantation was 1860 days. Kaplan-Meier patient survival was 92% at 1 year and 88% at 5 years. The actuarial risk of HBV recurrence was 1% at 1 year and 4% at 5 years. Baseline HBV DNA titer was associated with HBV recurrence. CONCLUSION: Low-dose IM HBIG plus lamivudine provides safe and effective long-term prophylaxis against recurrent HBV at <10% the cost of the high-dose regimen.     

High-dose hepatitis B immunoglobulin therapy in hepatocellular carcinoma with hepatitis B virus-DNA/hepatitis B e antigen-positive patients after living donor liver transplantation

AIM: To investigate the impact of high-dose hepatitis B immunoglobulin(HBIG) on hepatocellular carcinoma(HCC) and hepatitis B virus(HBV) recurrence and overall survival after living donor liver transplantation(LDLT).METHODS: We investigated 168 patients who underwent LDLT due to HCC, and who were HBV-DNA/hepatitis B e antigen(HBe Ag)-positive, from January 2008 to December 2013. After assessing whether the patients met the Milan criteria, they were assigned to the low-dose HBIG group and high-dose HBIG group. Using the propensity score 1:1 matching method, 38 and 18 pairs were defined as adhering to and not adhering to the Milan criteria. For each pair, HCC recurrence, HBV recurrence and overall survival were analyzed by the Kaplan-Meier method and the log rank test according to the HBIG dose. RESULTS: Among those who met the Milan criteria, the 6-mo, 1-year, and 3-year HCC recurrence-free survival rates were 88.9%, 83.2%, and 83.2% in the low-dose HBIG group and 97.2%, 97.2%, and 97.2% in the high-dose HBIG group, respectively(P = 0.042).In contrast, among those who did not meet the Milan criteria, HCC recurrence did not differ according to the HBIG dose(P = 0.937). Moreover, HBV recurrence and overall survival did not differ according to the HBIG dose among those who met(P = 0.317 and 0.190, respectively) and did not meet(P = 0.350 and 0.987, respectively) the Milan criteria. CONCLUSION: High-dose HBIG therapy can reduce HCC recurrence in HBV-DNA/HBe Ag-positive patients after LDLT.     

Hepatitis B and Liver Transplantation: Update in Management before and after Transplantation

Patients who undergo liver transplantation (LT) for chronic hepatitis B virus (HBV) infection are at high risk of developing recurrent HBV in the absence of effective prophylaxis. Pre-LT management should focus on suppression of HBV DNA levels, which have been associated with HBV recurrence. Evidence linking hepatocellular carcinoma (HCC) recurrence to HBV recurrence has been less clear. Prophylaxis against recurrent HBV after LT with combination HBIG and antiviral therapy is the current standard of care and is effective in >90% of patients, but investigation is ongoing to determine the most cost-effective treatment regimens. While antiviral therapy with newer nucleos(t)ide analogues without HBIG is assumed to be effective, no recent studies have examined the long-term efficacy of salvage regimens for recurrent HBV. Large, prospective trials are urgently needed. Overall, LT for HBV is highly effective with appropriate pre- and post-LT antiviral therapy.     

Prophylaxis against hepatitis B virus recurrence after liver transplantation: A registry study

AIM: To evaluate the prophylactic efficacy of hepatitis B immunoglobulin(HBIG) in combination with different nucleos(t)ide analogues.METHODS: A total of 5333 hepatitis B surface antigenpositive patients from the China Liver Transplant Registry database were enrolled between January 2000 and December 2009. Low-dose intramuscular(im) HBIG combined with one nucleos(t)ide analogue has been shown to be very cost-effective in recent reports. Hepatitis B virus(HBV) prophylactic outcomes were compared based on their posttransplant prophylactic protocols [group A(n = 4684): im HBIG plus lamivudine; group B(n = 491): im HBIG plus entecavir; group C(n = 158): im HBIG plus adefovir dipivoxil]. We compared the related baseline characteristics among the three groups, including the age, male sex, Meld score at the time of transplantation, Child-Pugh score at the time of transplantation, HCC, pre-transplantation hepatitis B e antigen positivity, pre-transplantation HBV deoxyribonucleic acid(HBV DNA) positivity, HBV DNA at the time of transplantation, pre-transplantation antiviral therapy, and the duration of antiviral therapy before transplantation of the patients. We also calculated the 1-, 3- and 5-year survival rates and HBV recurrence rates according to the different groups. All potential risk factors were analyzed using univariate and multivariate analyses.RESULTS: The mean follow-up duration was 42.1 ± 30.3 mo. The 1-, 3- and 5-year survival rates were lower in group A than in groups B(86.2% vs 94.4%, 76.9% vs 86.6%, 73.7% vs 82.4%, respectively, P 0.001) and C(86.2% vs 92.5%, 76.9% vs 73.7%, 87.0% vs 81.6%, respectively, P 0.001). The 1-, 3-and 5-year posttransplant HBV recurrence rates were significantly higher in group A than in group B(1.7% vs 0.5%, 3.5% vs 1.5%, 4.7% vs 1.5%, respectively, P = 0.023). No significant difference existed between groups A and C and between groups B and C with respect to the 1-, 3- and 5-year HBV recurrence rates. Pretransplant hepatocellular carcinoma, high viral load and posttransplant prophylactic protocol(lamivudine and HBIG vs entecavir and HBIG) were associated with HBV recurrence.CONCLUSION: Low-dose intramuscular HBIG in combination with a nucleos(t)ide analogue provides effective prophylaxis against posttransplant HBV recurrence, especially for HBIG plus entecavir.     

Adefovir dipivoxil therapy in liver transplant recipients for recurrence of hepatitis B virus infection despite lamivudine plus hepatitis B immunoglobulin prophylaxis

BACKGROUND: Treatment of post-transplantation recurrence of hepatitis B virus (HBV) infection despite prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine combination therapy is not easy. Because HBV reinfection has a severe course and could result in graft failure in liver transplant recipients, prompt medication is essential. Herein is reported the authors' experience with adefovir dipivoxil (AD) therapy in 11 liver transplant recipients who had HBV reinfection despite the administration of lamivudine and HBIG. METHOD: Two-hundred and nine patients underwent liver transplantation (100 deceased donor liver transplantations [DDLT], 109 living donor liver transplantation [LDLT]) due to chronic hepatitis B infection between April 1997 and May 2005 in Ege University Medical School, Liver Transplantation Unit. Patients had prophylaxis with lamivudine and low-dose HBIG combination after liver transplantation. Treatment of recurrence consisted of AD 10 mg once a day and lamivudine 300 mg/daily and HBIG was discontinued in those patients. RESULTS: In total there were 11 HBV recurrences: five occurred in DDLT recipients and six in LDLT recipients, at a median follow up of 18 months (range, 6-48 months). In one of 11 patients, pretransplant HBV-DNA and HBeAg were positive. Three patients had a severe course and one patient had fibrosing cholestatic hepatitis. After AD treatment, HBV-DNA level decreased in all patients and became negative in seven patients. Two patients died due to hepatocellular carcinoma recurrence after 12 and 14 months of follow up. Serum creatinine level increased mildly in one patient and no other side-effect was observed, and all patients continued therapy. CONCLUSION: Adefovir dipivoxil is a safe, effective treatment option for post-transplant HBV recurrence even among patients with fibrosing cholestatic hepatitis caused by lamivudine-resistant HBV.