拉米夫定及乙型肝炎免疫球蛋白预防肝移植后乙型肝炎复发的疗效观察

目的:研究单用拉米夫定或与乙型肝炎(乙肝)免疫球蛋白(HBIG)联合应用对乙肝相关肝病病人肝移植术后预防乙肝复发的效果。方法:应用酶联免疫试验(EIA)检测HBsAg、抗鄄HBs、HBeAg、抗鄄HBe及抗鄄HBc;用聚合酶链反应法(PCR)检测乙肝病毒(HBV)DNA。26例单用拉米夫定15例,联合应用拉米夫定和HBIG11例。结果:26例乙肝相关肝病病人于肝移植术后随访3～24个月,2例死亡,4例出现乙肝复发,其余20例病人HBsAg持续阴性。结论:肝移植是治疗乙肝终末期病人的有效方法,拉米夫定与HBIG联合应用可有效预防肝移植术后乙肝复发。     

肝移植术后乙肝复发的预防与处理

目的总结和探讨肝移植术后乙肝复发的预防与处理。方法回顾性分析253例乙肝相关性肝病行肝移植术患者乙肝防治方法、术后乙肝复发的处理。结果术后乙肝复发者7例,复发率2.76%。复发后分别采用加大乙肝免疫球蛋白(HB IG)剂量、改用恩替卡韦、加用贺维力等措施,2例HBsAg经治疗后转阴,2例HBsAg明显下降,总有效率57%。结论肝移植术后HB IG 拉米夫丁能有效预防肝移植术后乙肝复发,HB IG、恩替卡韦、贺维力能不同程度控制肝移植术后乙肝复发。     

恩替卡韦联合乙肝免疫球蛋白预防肝移植术后乙肝复发

肝移植是乙肝相关终末期肝病的最主要适应证,而肝移植术后乙肝复发则是影响肝移植受者长期生存的主要原因之一.文献报道,拉米夫定联合乙型肝炎免疫球蛋白(hepatitis B immuno globulin,HBIG)预防移植术后乙肝复发,其1年复发率为2.1%～13.5%,2年复发率为4.5%～15.2%[1-2].目前,用恩替卡韦联合HBIG预防肝移植后乙肝复发的文献报道较少.本文对我中心2007年1月至2009年4月采用恩替卡韦联合HBIG以及拉米夫定联合HBIG预防肝移植术后乙肝复发的104例临床资料进行了回顾性分析.     

小剂量乙肝免疫球蛋白(HBIG)联合拉米夫定(LAM)防治肝移植术后乙肝复发的应用研究

肝移植术后乙肝再感染与复发导致移植肝失功严重地影响了病人的预后。因此，防治乙肝复发已成为临床急需解决的重要课题。研究报告乙肝免疫球蛋白联合拉米夫定在防治乙肝复发方面具有较大优势。现将我院采用该治疗方案防治乙肝复发的临床效果进行总结分析。     

肝移植术后乙型肝炎复发的预防和治疗

目的探讨拉米夫定联合低剂量乙型肝炎（乙肝）免疫球蛋白（HBIG）预防肝移植术后乙肝复发的效果及乙肝复发后的治疗。方法对2000年12月至2003年5月因乙肝相关性终末期肝病和（或）合并肝细胞癌于我院接受肝移植手术并经随访的11例患者进行回顾性分析。所有患者均接受拉米夫定联合低剂量HBIG预防乙肝复发方案。观察术后近期乙肝转阴情况、术后较远期乙肝复发情况以及乙肝复发后的治疗情况。结果（1）所有患者HBsAg、HBeAg、HBV-DNA均于术后1-4d转为阴性,术后1周所有患者对HBIG均有反应,HBsAb滴度水平逐渐上升;（2）所有患者于观察期内生存情况均良好,对患者HBsAb滴度水平定期进行监测结果示大部分患者HBsAb滴度水平与预期治疗水平基本符合;（3）1例患者于术后25个月乙肝复发,通过改用阿德弗韦并加大HBIG用量,基本得到控制。结论拉米夫定联合低剂量HBIG预防肝移植后乙肝复发疗效确切,而且可显著降低治疗费用。     

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。     

重建主动免疫预防肝移植术后乙肝复发的临床应用前景

乙肝相关肝病目前仍是肝移植的主要指征。在现有的小剂量乙肝免疫球蛋白（hepatitis B immune globulin,HBIG）联合拉米夫丁（lamivudine,LAM）预防方案的保护下,乙肝相关肝病肝移植术后5年乙肝病毒再感染/乙肝复发的总体发生率已能控制于5%以下。基于HBIG＋LAM的良好效果,近10年来临床已将其作为肝移植术后预防乙肝复发的＂金标准＂。但是,该方案也存在某些缺陷或不足。     

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。     

联合应用拉米呋定和乙肝免疫球蛋白预防肝移植术后乙肝复发的疗效观察

目的观察联合应用拉米呋定和小剂量乙肝免疫球蛋白预防肝移植术后乙肝复发的临床疗效。方法回顾性分析35例乙肝病毒（hepatitis B virus．HBV）相关终末期肝病患者行肝移植术后联合应用拉味夫定和小剂量乙肝免疫球蛋白的临床资料．观察此方案对预防肝移植术后乙肝病毒再感染的疗效。结果4例肝移植术后发生乙肝复发,复发率11％．其余31例病毒标志物均为阴性。结论联合应用拉米呋定和小剂量乙肝免疫球蛋白可以有效地预防乙肝病毒相关终末期肝病肝移植术后乙肝复发,小样本短期随访效果满意,有待于进一步大样本长期观察     

肝移植患者采取不同的方法应用乙型肝炎免疫球蛋白的随机和对照研究

目的研究肝移植患者术中和术后早期经不同方法应用乙型肝炎免疫球蛋白（HBIG）对血清乙型肝炎表面抗原（HBsAg）、乙型肝炎e抗原（HBeAg）和乙型肝炎病毒（HBV）-DNA阴转速度的影响。方法将入选的乙型肝炎相关性肝病肝移植患者随机分为3组，每组30例。静脉注射组（静注组）：通过静脉注射给予HBIG；肌肉注射组（肌注组）：通过肌肉注射给予HBIG；序贯给药组（序贯组）：即先静脉注射后肌肉注射给予HBIG。每组均在联合使用拉米夫定的情况下，于术中和术后6d内给予相同剂量的HBIG。术后7d内动态观察HBsAg、HBeAg和HBV-DNA的血清学转化情况。结果静注组和序贯组血清HBV-DNA在术后第2天全部转阴，肌注组第4天全部转阴。静注组和序贯组HBeAg于第3天全部转阴，肌注组于第4天全部转阴。静注组和序贯组HBsAg于第4天全部转阴，而肌注组经在第4天和第5天追加HBIG用量后，于第6天才全部转阴；静注组和序贯组术后5d内每个时间点HBsAg的阴转率都显著高于肌注组（P〈0．05）。结论静脉给药和序贯给药的血清HBV-DNA、HBeAg及HBsAg的阴转速度都显著快于肌肉注射给药，而序贯给药不仅能获得静脉给药的等同效果，且简单、易行，是一种更为合理的给药方法。     

肝移植术后乙肝复发的临床特点分析

目的探讨肝移植术后乙肝复发的特点和治疗的可行性。方法回顾性分析2例肝移植术后乙肝复发病例和1例移植后早期血清HBsAg( )、HBV-DNA( )病例的临床诊疗经过,分析比较肝移植术后乙肝复发的临床特点。结果2例肝移植乙肝复发病例治疗后乙肝病毒未能清除,1例移植后早期血清HBsAg( )、HBV-DNA( )病例治疗后乙肝病清除。结论肝移植术后乙型肝炎病毒变异和肝移植术前高病毒量是移植术后乙肝复发的重要原因;移植术后及时的病理能够提示抗病毒治疗结果。     

重型乙型肝炎肝移植术后乙型肝炎病毒再感染的防治

目的探讨重型乙型肝炎肝移植术后乙型肝炎病毒(HBV)再感染的防治。方法回顾性分析了73例重型乙型肝炎患者,移植前后给予抗病毒药物预防乙型肝炎病毒再感染,拉米夫定 乙肝免疫球蛋白(HBIG)71例,阿德夫韦 拉米夫定 乙肝免疫球蛋白2例,观察临床表现、血清HBSAg、血清HBeAg、血清HBV DNA及肝活检免疫组织化学检测等指标。结果应用拉米夫定 HBIG预防的71例中,有2例再感染,血清HBSAg为阳性,肝活检免疫组织化学检测有HBSAg表达,其中1例血清HBV DNA阳性,另1例经治疗后HBSAg又转阴。用阿德夫韦 拉米夫定 HBIG预防的2例中,血清学和肝活检免疫组织化学检测均无HBSAg表达。结论拉米夫定 HBIG或拉米夫定 阿德夫韦 HBIG联合应用以及合理的使用免疫抑制剂可以有效预防重型乙型肝炎患者移植术后乙型肝炎病毒的再感染。     

Hepatitis B surface antigenemia following recombinant Engerix B hepatitis B vaccine in an 81-year-old ESRD patient on hemodialysis

The first cases of transient hepatitis B surface antigenemia (HBsAg) in adults following hepatitis B virus (HBV) immunization were reported in the 1990s. HBV immunization is mandatory for all hemodialysis (HD) patients. Ly et al. who demonstrated transient HBsAg in eight out of nine HD patients following HBV vaccine concluded that HD patients should not be screened for HBV within a week of HBV immunization and that positive HBsAg within a month of HBV immunization must be interpreted with caution. We present an 81-year-old woman on HD, who needed a booster Recombivax (Merck, Whitehouse Station, NJ, USA) vaccine after remaining hepatitis B surface antibody (HBsAb) negative from previous vaccinations. The HD Unit had switched to Engerix B (GlaxoSmithKline, Atlanta, GA, USA) HBV vaccine. Two days after the first Engerix B vaccine, HBsAg was detected. She was asymptomatic; ALT was 25 U/L. Repeat testing for HBsAg, HBsAb, hepatitis B E antigen (HB E Ag), and hepatitis B DNA (HB DNA), a week later, all returned negative. Previous reports of transient HBsAg following HBV vaccines were after Engerix B vaccination. Our patient is unusual since she had received both brands of HBV vaccines, sequentially, at different times. Twice, HBsAg tests completed as early as 5 days following Recombivax vaccine were negative. We submit that positive HBsAg tests are more likely following Engerix B vaccines. We reemphasize previous recommendations that patients should not be screened for HBsAg < 4 weeks following HBV immunization. This is particularly important in HD units where hepatitis B screening is carried out routinely all year round and hepatitis B vaccinations are commonplace. Very strict schedules must be adopted to avoid false positive HBsAg tests.     

乙型肝炎产妇乳汁乙肝病毒标志物检测与哺乳指导

目的：探讨乙型肝炎产妇产后能否进行母乳喂养。方法：选择住院分娩 的乙型肝炎产妇150例（肝功能均正常），其中血清HBsAg阳性79例为单阳组，HBsAg及HBeAg均阳性71例为双阳组，分别留取产后3－5d的初乳进行乳汁乙肝病毒标志物（HBV－M）检测，结果：两组乳汁中HBsAg,HBeAg,HBcAb,HBV DNA阳性率比较，差异有显著性意义（P＜0．05），结论：根据HBV－M各项指标阳性的临床价值分析产妇初乳中HBeAg,HBV DNA阳性及产妇血清中双阳者（HBsAg,HBeAg阳性）不宜哺乳，初乳中单纯HBsAg阳性，而HBV DNA为阴性的产妇可以哺乳，但应给予正确的哺乳指导。     

Long-term lamivudine monotherapy prevents development of hepatitis B virus infection in hepatitis B surface-antigen negative liver transplant recipients from hepatitis B core-antibody-positive donors

BACKGROUND: Liver transplantation from hepatitis B core-antibody (HBcAb)-positive donors to hepatitis B surface-antigen (HBsAg)-negative recipients has been associated with a risk of hepatitis B virus (HBV) infection in the absence of antiviral prophylaxis. The aim of this study is to assess the efficacy of long-term lamivudine monotherapy to prevent development of HBV infection in HBsAg-negative recipients of liver allografts from HBcAb-positive donors. METHODS: From 315 cadaveric adult liver transplantations performed at our unit between July 1999 and March 2005, 18 recipients (5.7%) received liver allografts from HBcAb-positive donors, 13 of whom were HBsAg-negative pre-transplantation. The recipients consisted of four females and 14 males, age range 28-65 yr (median 49.5 yr). Post-transplantation, HBsAg-negative recipients were administered lamivudine 100 mg daily long term. HBsAg-positive recipients were administered low-dose hepatitis B immunoglobulin (HBIg) and lamivudine according to our usual protocol. Standard post-transplantation immunosuppression was given. Recipients were followed up regularly (range 2-69 months, median 21 months) for development of de novo HBV infection. RESULTS: Ten HBsAg-negative recipients received long-term lamivudine. One patient (HBcAb and HBsAb positive pre-transplant) did not receive lamivudine and, in two patients, lamivudine was discontinued following urgent re-transplantation for primary graft non-function. All 13 of the HBsAg-negative recipients were still alive, with no evidence of HBV infection at the end of follow-up. CONCLUSION: Long-term lamivudine monotherapy was effective in preventing development of HBV infection in HBsAg-negative liver transplant recipients from HBcAb-positive donors.     

乙型肝炎病毒基因型与肝细胞癌发生关系的研究现状

目的总结目前国内外对乙型肝炎病毒X蛋白(HBx)、乙型肝炎病毒(HBV)基因亚型和肝细胞癌三者之间关系的研究现状,并对其在临床工作中的意义进行展望。方法查阅近年来国内外关于HBx、HBV基因亚型和肝细胞癌研究的相关文献并加以综述。结果 HBx和肝细胞癌的发生、发展、迁徙以及转移之间有着密切的关系,HBV基因亚型与肝细胞癌存在一定的关联,但具体机制尚未阐明。结论 HBx和HBV基因亚型在肝细胞癌的发生发展过程中扮演着重要的角色,随着分子机制的不断深入研究,必将推动乙型肝炎、肝硬化和肝细胞癌的诊治工作,为临床工作者提供更为个体化的干预手段。     

Long‐term outcome of patients with lamivudine after early cessation of hepatitis B immunoglobulin for prevention of recurrent hepatitis B following liver transplantation

Yuefeng M, Weili F, Wengxiang T, Ligang X, Guiling L, Hongwei G, Wencai L, Xiaoguang W, Wei M, Zhongyi F. Long‐term outcome of patients with lamivudine after early cessation of hepatitis B immunoglobulin for prevention of recurrent hepatitis B following liver transplantation.
Clin Transplant 2011: 25: 517–522. © 2010 John Wiley & Sons A/S. Abstract: Background: The aim of this study is to examine the efficacy of long‐term prophylaxis with lamivudine (LAM) after a course of post‐operative hepatitis B immunoglobulin (HBIG) in patients who underwent liver transplantation (LT) for hepatitis B virus (HBV)‐related disease. Result: The medical records of HBV‐infected patients who underwent a LT in our institution between July 2001 and May 2005 were reviewed. There were 15 liver transplant recipients who were administered HBIG for <18 months and used LAM as a maintenance prophylaxis regime enrolled in this study. At enrollment, all patients were hepatitis B surface antigen (HBsAg) positive and three patients were HBeAg positive. There were 13 patients who were HBV DNA positive with a mean viral load of 5.4 log copies/mL, and among them, 12 recipients were on antiviral therapy with LAM (100 mg/d orally) for 12–168 d, resulting in HBV DNA negative levels in nine patients prior to their transplant. HBV recurrence post‐LT was noted in two patients who had very high‐HBV DNA levels pre‐LT. Both of these patients showed LAM‐resistant mutation at the time of recurrence. The 11 patients who were HBV DNA negative before LT (low‐risk patients) had no HBV recurrence during a follow‐up at a median of 58 months post‐LT. This included five patients who had intermittent low‐level HBV DNA post‐LT (HBsAg negative), of whom two had YMDD mutation and these two were given adefovir in addition to LAM. Conclusion: Our retrospective study demonstrated excellent long‐term outcomes in the low‐risk patients treated with LAM after a short course of HBIG.     

Prevalence of hepatitis B and hepatitis C in haemodialysis patients

The prevalence of hepatitis B surface antigen (HBsAg), hepatitis B exposure and antibodies against the hepatitis C virus (anti-HCV) was assessed in 86 haemodialysis patients at the National Kidney and Transplant Institute (NKTI) using the commercial radioimmunoassay and ortho HCV ELISA assay. Of the 86 patients included in the study, 42 were male with a mean age of 44.9 years and a mean duration of dialysis of 2.4 years. Forty-four were female with a mean age of 48.4 years and a mean duration of dialysis of 2.3 years. Hepatitis B exposure was 57% and 12.8% of haemodialysis patients were positive for HBsAg, whereas 39.8% of patients were positive for anti-HCV. There was a significant correlation ( P =0.00007) between anti-HCV positivity and the length of time on haemodialysis. However, there was no significant correlation found between the number of blood transfusions received and anti-HCV positivity. There was also no significant correlation found between HBsAg and antibodies to hepatitis B core antigen (anti-HBc) positivity and the number of blood transfusions or the length of time on haemodialysis, nor between hepatitis B and C exposure and elevated aminotransferase levels.     

Prevalence of hepatitis B and hepatitis C in haemodialysis patients

SUMMARY: The prevalence of hepatitis B surface antigen (HBsAg), hepatitis B exposure and antibodies against the hepatitis C virus (anti-HCV) was assessed in 86 haemodialysis patients at the National Kidney and Transplant Institute (NKTI) using the commercial radioimmunoassay and ortho HCV ELISA assay. of the 86 patients included in the study, 42 were male with a mean age of 44.9 years and a mean duration of dialysis of 2.4 years. Forty-four were female with a mean age of 48.4 years and a mean duration of dialysis of 2.3 years. Hepatitis B exposure was 57% and 12.8% of haemodialysis patients were positive for HBsAg, whereas 39.8% of patients were positive for anti-HCV. There was a significant correlation ( P = 0.00007) between anti-HCV positivity and the length of time on haemodialysis. However, there was no significant correlation found between the number of blood transfusions received and anti-HCV positivity. There was also no significant correlation found between HBsAg and antibodies to hepatitis B core antigen (anti-HBc) positivity and the number of blood transfusions or the length of time on haemodialysis, nor between hepatitis B and C exposure and elevated aminotransferase levels.