Clinical study on prevention of HBV re-infection by entecavir after liver transplantation

Cai C‐j, Lu M‐q, Chen Y‐h, Zhao H, Li M‐r, Chen G‐h. Clinical study on prevention of HBV re‐infection by entecavir after liver transplantation.
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01448.x.
© 2011 John Wiley & Sons A/S. Abstract: Purpose: This aims to evaluate the effects of lamivudine (LAM) and entecavir (ETV) in preventing hepatitis B virus (HBV) re‐infection after liver transplantation (LT). Methods:  A retrospective matched case‐control method was used in this study. From June 2005 to May 2007, the patients who received LAM (100 mg qd) or ETV (0.5 mg qd) were chosen. The LAM and ETV groups were matched using a 3:1 ratio based on the factors, such as age, gender, LAM or ETV antiviral duration, primary disease, and HBV DNA levels at the initiation of antiviral therapy. Data on serum HBV markers, HBV DNA, and cumulative recurrence were collected. Results: Two hundred and fifty‐two patients were enrolled. The average duration of follow‐up was 38.5 and 41.2 months (LAM and ETV groups) (p > 0.05). Duration of pre‐operative antiviral therapy was 30.3 and 25.8 d (LAM and ETV groups) (p > 0.05). The HBV DNA level decreased from 3.89 × 10⁶ to 5.31 × 10⁵ copies/mL before LT in the LAM group, and decreased from 8.74 × 10⁶ to 5.49 × 10⁴ copies/mL in the ETV group (p < 0.05). Eighteen patients in LAM group developed HBV re‐infection and 0 in ETV group. Conclusion: ETV is superior to LAM for preventing HBV re‐infection following LT.     

Use of telbivudine in kidney transplant recipients with chronic hepatitis B virus infection: A preliminary experience

Telbivudine is a relatively novel oral nucleoside analogue with favourable efficacy and tolerability in treatment‐naïve chronic hepatitis B virus (HBV) infection, but its data in kidney transplant recipients (KTRs) was lacking. The efficacy and tolerability of telbivudine in four treatment‐naïve HBsAg‐positive KTRs were reviewed (treatment duration 54 (36–72) months) HBV DNA declined from 2.6 × 10⁵(7.8 × 10³–1.5 × 10⁷) copies/mL at baseline to 170 (0.0–3.2 × 10⁴) copies/mL at 12 months, and became undetectable at 24 and 36 months (P = 0.060, 0.118 and 0.005 compared with baseline). Alanine aminotransferase levels dropped from 46.5 (30–48) IU/mL at baseline to 28 (13–45) IU/mL, 34.5 (15–71) IU/mL and 26 (12–41) IU/mL at 12, 24 and 36 months, respectively (P = 0.109, 0.715 and 0.068 compared with baseline). Serum creatinine level and estimated glomerular filtration rate (eGFR) remained stable after 36 months of treatment (P all > 0.05 compared with baseline). No virological breakthrough, cirrhosis or hepatocellular carcinoma occurred. Our pilot data suggests that telbivudine has favourable efficacy and renal safety profiles in HBsAg‐positive KTRs.     

拉米夫定应答不佳慢性乙型肝炎患者加用阿德福韦酯与换用恩替卡韦疗效比较

目的比较拉米夫定应答不佳慢性乙型肝炎（CHB）患者加用阿德福韦酯联合治疗与换用恩替卡韦单药治疗48周疗效。方法采用前瞻性研究方法观察2010年6月—2011年6月在浙江省诸暨市人民医院感染科和浙江大学医学院附属第一医院接受拉米夫定抗病毒治疗24周以上,但HBVDNA仍阳性的住院及门诊CHB患者120例,以随机数字表法将患者分为两组,每组各60例,一组在用拉米夫定的基础上加用阿德福韦酯联合抗病毒治疗,另一组则换用恩替卡韦单药治疗,疗程均为48周。每1～3个月检测患者的肝功能、肾功能、甲胎蛋白、HBV血清学标志物、HBVDNA、凝血酶原时间（PT）、肝脏的超声波或行CT检查。采用χ2检验比较治疗48周时两组的病毒学、血清学的应答率和耐药发生率,观察两组的不良反应。结果基线HBVDNA介于3～5lg拷贝／mL的拉米夫定应答不佳者,加用阿德福韦酯治疗至48周后有86．8％（33／38）的患者HBVDNA转阴,而换用恩替卡韦单药治疗组有69．2％（27／39）的患者转阴,两组比较差异具有统计学意义（χ2=4．578,P〈0．05）;基线HBVDNA〉5lg拷贝／mL的拉米夫定应答不佳者,加用阿德福韦酯的患者HBVDNA转阴率为72．7％（16／22）,而换用恩替卡韦单药治疗患者只有52．4％（11／21）,两组差异也具有统计学意义（χ2=4．865,P〈0．05）。拉米夫定应答不佳者经加用阿德福韦酯联合治疗后48周无一例发生病毒学突破,也无耐药的发生;而换用恩替卡韦治疗组则有5例发生病毒学突破,3例检测到基因突变,其中2例为rtM204V、rtL180M和rtS202G变异,1例为rtM204V、rtL180M和rtT184A,所有发生基因突变的病例均为基线HBVDNA〉10。拷贝／mL者。结论拉米夫定应答不佳CHB患者加用阿德福韦酯比换用恩替卡韦单药治疗更能抑制HBV复制,且可减少病毒耐药的发生。     

New nucleos(t)ide analogue monoprophylaxis after cessation of hepatitis B immunoglobulin is effective against hepatitis B recurrence

New nucleos(t)ide agents (NAs) [entecavir (ETV) and tenofovir (TDF)] have made hepatitis B immunoglobulin (HBIG)‐sparing protocols an attractive approach against hepatitis B virus (HBV) recurrence after liver transplantation (LT). Twenty‐eight patients transplanted for HBV cirrhosis in our centre were prospectively evaluated. After LT, each patient received HBIG (1000 IU IM/day for 7 days and then monthly for 6 months) plus ETV or TDF and then continued with ETV or TDF monoprophylaxis. All patients had undetectable HBV DNA at the time of LT, and they were followed up with laboratory tests including glomerular filtration rate (GFR) after LT. All patients (11 under ETV and 17 under TDF) remained HBsAg/HBV DNA negative during the follow‐up period [median: 21 (range 9–43) months]. GFR was not different between TDF and ETV groups of patients at 6 and 12 months and last follow‐up (P value >0.05 for all comparisons). The two groups of patients were similar regarding their ratio of maximum rate of tubular phosphate reabsorption to the GFR (TmP/GFR). In conclusion, in this prospective study, we showed for the first time that maintenance therapy with ETV or TDF monoprophylaxis after 6 months of low‐dose HBIG plus ETV or TDF after LT is highly effective and safe.     

High Genetic Barrier Nucleos(t)ide Analogue(s) for Prophylaxis From Hepatitis B Virus Recurrence After Liver Transplantation: A Systematic Review

The combination of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues [NA(s)] is considered as the standard of care for prophylaxis against HBV recurrence after liver transplantation (LT), but the optimal protocol is controversial. We evaluated the efficacy of the newer NAs with high genetic barrier (hgbNA) [i.e. entecavir (ETV) or tenofovir (TDF)] with or without HBIG as prophylaxis against HBV recurrence after LT. In total, 519 HBV liver transplant recipients from 17 studies met the inclusion criteria and they were compared to those under lamivudine (LAM) and HBIG who had been selected in our previous review. Patients under HBIG and LAM developed HBV recurrence (115/1889 or 6.1%): (a) significantly more frequently compared to patients under HBIG and a hgbNA [1.0% (3/303), p < 0.001], and (b) numerically but not significantly more frequently compared to the patients who received a newer NA after discontinuation of HBIG [3.9% (4/102), p = 0.52]. The use of a hgbNA without any HBIG offered similar antiviral prophylaxis compared to HBIG and LAM combination, if the definition of HBV recurrence was based on HBV DNA detectability [0.9% vs. 3.8%, p = 0.11]. Our findings favor the use of HBIG and a hgbNA instead of HBIG and LAM combined prophylaxis against HBV recurrence after LT.     

Antiviral treatment for hepatitis B virus recurrence following liver transplantation

The purpose of this study was to identify the factors associated with the recurrence of hepatitis B virus (HBV) following liver transplantation (LT) for HBV‐related disease and to recognize the outcome of treatment for HBV recurrence with oral nucleos(t)ide analogues. Six hundred and sixty‐seven LTs were performed for HBsAg‐positive adult patients in our institute from 1996 to 2010. HBV prophylaxis was performed by hepatitis B immunoglobulin (HBIG) monotherapy or HBIG and entecavir combination therapy. There were 63 cases (11.4%) of HBV recurrences during a median follow‐up of 51 months. The median time to HBV recurrence was 22 months. A preoperative HBV DNA load of more than 10⁵ IU/mL, HBIG monotherapy, and hepatocellular carcinoma in the explant liver were independent risk factors for HBV recurrence following LT in multivariate analysis. Patient survival at 10 yr was 54.2% for HBV‐recurrent patients. Among patients with HBV recurrence, HBsAg seroclearance was achieved in 13 patients (20.6%), but HBsAg seroclearance did not affect survival in these patients after the recurrence of HBV (p = 0.28). The recurrence of HBV led to graft failure in six cases. HBV recurrence should be prevented by strict management of pre‐transplant HBV viremia and an effective post‐transplant HBV prophylaxis.     

Hepatitis B virus vaccination of recipients and donors of allogeneic peripheral blood stem cell transplantation

Abstract: Background: The aim of this study was to determine the role of hepatitis B virus (HBV) vaccination as defined by the seroconversion to hepatitis B surface antibody (anti‐HBs) positivity in peripheral blood stem cell transplants. Methods: A total of 65 recipients and their donors were enrolled in this study. Recipients were divided into four distinct groups. Group 1 consisted of individuals who were vaccinated, group 2 consisted of individuals who were naturally immunized, group 3 consisted of individuals who were HBs‐Ag positive, and group 4 consisted of individuals who were HBV naïve and not vaccinated. Results: Eighty‐eight percent of the HBV‐vaccinated recipients (14 of 16), who had vaccinated‐donors, seroconverted to anti‐HBs positivity. Eighty‐three percent of HBV‐naïve recipients (five of six), who received stem cells from HBV‐immune donors, seroconverted to anti‐HBs positivity. Two of the four HBs‐Ag positive recipients with HBV‐immune donors seroconverted to anti‐HBs positivity after transplantation. Fifty‐seven percent of previously vaccinated‐recipients (eight of 14) lost detectable anti‐HBs antibody following transplantation. Finally, 31% of HBV‐naïve recipients with HBV‐naïve donors acquired a de novo HBV infection. Conclusions: (i) Hepatitis B virus immunization of recipients of allogeneic hematopoietic cell transplantation results in an effective antibody response. (ii) The HBV‐immune status of the donor plays an important role in post‐transplantation HBs‐Ab on seroconversion. (iii) Systematic re‐immunization of recipients will be necessary to maintain HBV immunity in long‐term serving recipients.     

恩替卡韦治疗慢性乙型肝炎48周疗效观察

目的以拉米夫定（LAM）为对照,观察恩替卡韦（ETV）治疗慢性乙型肝炎（CHB）的抗病毒疗效。方法84例CHB患者,分为ETV组（0.5mg/d）和LAM组（100mg/d）各42例,用药时间至少48周。于第4、12、24和48周时,分别检测丙氨酸氨基转移酶（ALT）水平及应用PCR定量法检测血清病毒载量。治疗前和治疗48周时分别检测乙型肝炎病毒血清学指标。结果经过48周治疗后ALT的复常率,ETV组为90.5%,LAM组为73.8%（P＆lt;0.05）;HBV DNA＆lt;103拷贝/ml的患者比例,ETV组为92.7%,LAM组为71.4%（P＆lt;0.05）,ETV组均优于LAM组。两组患者HBeAg血清转换率差别无统计学意义,而HBeAg低于检测下限的比率ETV组（39.4%）高于LAM组（17.7%）（P＆lt;0.05）。治疗48周时ETV组无1例患者出现病毒反弹,而LAM组有8例（19.0%）出现病毒反弹,经检测系YMDD变异。结论ETV治疗CHB患者,在改善肝脏生化指标、抑制病毒、HBeAg低于检测下限和减少病毒变异方面均优于LAM。     

拉米夫定联合阿德福韦酯与恩替卡韦单药治疗失代偿期乙型肝炎肝硬化二年疗效比较

目的比较拉米夫定（LAM）与阿德福韦酯（ADV）初始联合与恩替卡韦（ETV）单药治疗失代偿期乙型肝炎肝硬化2年的疗效。方法选取2007年1月—2008年4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120例失代偿期乙型肝炎肝硬化患者作为研究对象,其中60例接受LAM联合ADV初始抗病毒治疗,60例接受ETV单药抗病毒治疗。每1～3个月检测患者肝功能、肾功能、甲胎蛋白、HBV血清学标志物、HBVDNA、凝血酶原时间（PT）、肝脏超声波或CT。采用重复测量方差分析和X检验比较两组在治疗12和24个月时的疗效、不良反应和累计生存率。结果LAM和ADV初始联合治疗组和ETV单药治疗组各有45例至随访结束。两组HBVDNA转阴率和ALT复常率在治疗12个月（X^2=2．12和2．88,P〉0．05）和24个月时（X^2=3．21和3．24,P〉0．05）差异均无统计学意义;治疗24个月时HBeAg血清学转换率分别为43．5％（10／23）和36．4％（8／22）,差异有统计学意义（X^2=4．09,P〈0．05）。治疗12个月和24个月后,LAM和ADV初始联合组分别有2例（4．4％）和3例（6．7％）发生病毒学突破,但均未检测到病毒学变异;ETV单药组分别有I例（2．2％）和2例（4．4％）发生病毒学突破,并在24个月检测到1例（2．2％）发生病毒变异。LAM＋ADV初始联合组和ETV组治疗24个月后分别与治疗前（基线）相比,Alb水平上升（F=18．9和17．3,P〈0．05）,TBil和ALT下降（F=16．5、17．1和23．7、24．8,P〈0．05）,PT缩短（F=22．7和24．5,P〈0．05）,CTP评分和MELD评分下降（F=18．5、17．8和24．2、23．8,P〈0．05）。LAM和ADV初始联合治疗组累计病死率（或肝移植）为16．7％（10／60）,ETV单药组累计病死率（或肝移植）为18．3％（11／60）。两组均未发现有血清肌酐超过正常值上限的病例。结论LAM与ADV初始联合或ETV单药治疗失代偿期乙型肝炎肝硬化患者均能明显抑制HBV复制,改善肝功能,降低病死率,且耐药变异率低;联合组HBeAg血清学转换率在24个月时高于单药组,两种方案在临床上均可使用。     

The impact of internet and simulation‐based training on transoesophageal echocardiography learning in anaesthetic trainees: a prospective randomised study

With the increasing role of transoesophageal echocardiography in clinical fields other than cardiac surgery, we decided to assess the efficacy of multi‐modular echocardiography learning in echo‐naïve anaesthetic trainees. Twenty‐eight trainees undertook a pre‐test to ascertain basic echocardiography knowledge, following which the study subjects were randomly assigned to two groups: learning via traditional methods such as review of guidelines and other literature (non‐internet group); and learning via an internet‐based echocardiography resource (internet group). After this, subjects in both groups underwent simulation‐based echocardiography training. More tests were then conducted after a review of the respective educational resources and simulation sessions. Mean (SD) scores of subjects in the non‐internet group were 28 (10)%, 44 (10)% and 63 (5)% in the pre‐test, post‐intervention test and post‐simulation test, respectively, whereas those in the internet group scored 29 (8)%, 59 (10)%, (p = 0.001) and 72 (8)%, p = 0.005, respectively. The use of internet‐ and simulation‐based learning methods led to a significant improvement in knowledge of transoesophageal echocardiography by anaesthetic trainees. The impact of simulation‐based training was greater in the group who did not use the internet‐based resource. We conclude that internet‐ and simulation‐based learning methods both improve transoesophageal echocardiography knowledge in echo‐naïve anaesthetic trainees.     

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.     

Simulation‐based teaching versus point‐of‐care teaching for identification of basic transoesophageal echocardiography views: a prospective randomised study

In recent years, the use of transoesophageal echocardiography has increased in anaesthesia and intensive care. We explored the impact of two different teaching methods on the ability of echocardiography‐naïve subjects to identify cardiac anatomy associated with the 20 standard transoesophageal echocardiography imaging planes, and assessed trainees' satisfaction with these methods of training. Fifty‐two subjects were randomly assigned to one of two groups: a simulation‐based and a theatre‐based teaching group. Subjects undertook video‐based tests comprised of 20 multiple choice questions on echocardiography views before and after receiving echocardiography teaching. Subjects in simulation‐ and theatre‐based teaching groups scored 40% (30–40 [20–50])% and 35% (30–40 [15–55])% in the pre‐test, respectively (p = 0.52). Following echocardiography teaching, subjects within both groups improved upon their pre‐test knowledge (p < 0.001). Subjects in the simulation‐based teaching group significantly outperformed their theatre‐based group counterparts in the post‐intervention test (p = 0.0002).     

Risk of de novo hepatitis in liver recipients from hepatitis-B core antibody-positive grafts - a systematic analysis

Skagen CL, Jou JH, Said A. Risk of de novo hepatitis in liver recipients from hepatitis‐B core antibody‐positive grafts – a systematic analysis.
Clin Transplant 2011: 25: E243–E249. © 2011 John Wiley & Sons A/S. Abstract: Many transplant programs utilize liver grafts from hepatitis‐B core antibody (HBcAb)‐positive and hepatitis‐B surface antigen (HBsAg)‐negative donors. However, there is risk for de novo hepatitis B (DNH) in recipients of these grafts. We reviewed 26 studies reporting the rates of DNH in recipients receiving HBcAb‐positive liver grafts. Four hundred and sixty‐two donor–recipient pairs were included to evaluate the risk of DNH stratified by the recipient’s immune status to hepatitis B and type of prophylactic therapy given, if any. The rate of DNH was highest (58%) in the stratum of hepatitis‐B (HBV) naïve recipients who did not receive prophylaxis. In HBV naïve recipients, prophylactic therapy (lamivudine and/or hepatitis‐B immunoglobulin – HBIG) reduced DNH to 11% (odds ratio [OR] = 11.1, 95% CI 4.98–25, p < 0.0001 for DNH without prophylaxis). Recipients with hepatitis‐B surface antibody (HBsAb) positivity had DNH rates of 18% without prophylaxis and 0% with prophylaxis (OR = 9.2, 95% CI 1.1–83.3, p = 0.039). Recipients with both HBsAb and HBcAb positivity had DNH rates of 4% without prophylaxis and 3% with prophylaxis (p = 1.00), while recipients with HBcAb positivity alone had DNH rates of 14% without prophylaxis and 3% with prophylaxis (p = 0.21). There was no significant difference between the types of HBV prophylaxis received whether lamivudine, HBIG or both. However, in the subgroup who received HBIG alone, rates of DNH were higher after cessation of HBIG prophylaxis compared to DNH rates with indefinite HBIG (p = 0.0002). In summary, the risk of DNH is highest for HBV naïve liver recipients from HBcAb‐positive donors. Recipients who are HBV naïve as well as those recipients with isolated HBsAb positivity derive significant benefit from HBV prophylaxis after transplantation with a HBcAb‐positive graft. The ideal prophylactic regimen for prevention of DNH is unclear, but based on our analysis of the literature, antivirals alone may suffice. More data are needed with the newer antivirals for hepatitis B.     

Real‐world effectiveness of fulvestrant monotherapy as first endocrine treatment in patients with metastatic breast cancer

Fulvestrant monotherapy is approved for postmenopausal women with hormone receptor‐positive, metastatic breast cancer (MBC) who progressed following antiendocrine therapy, or those with hormone receptor‐positive, human epidermal receptor 2‐negative advanced breast cancer (BC) not previously treated with endocrine therapy (ET). However, real‐world data are lacking. Retrospective reviews of 10 United States community oncology practices identified patients diagnosed with MBC between 1 January 2011 and 31 December 2015 who received fulvestrant as the first ET, either as initial therapy for metastatic disease or after progression following one line of chemotherapy. Endpoints were progression‐free survival (PFS) and overall survival (OS). Patients were classified as ET‐naïve or by relapse status following adjuvant ET (“early” recurrence during or ≤12 months of completing adjuvant ET, or “late” >12 months after completing adjuvant ET). Outcomes were evaluated using Kaplan‐Meier methods. Among 121 patients, median PFS (95% confidence interval) was 8.3 months (4.8‐12.3) for early relapse, 15.4 months (10.2‐21.2) for late relapse, and 18.7 months (10.1‐20.8) among ET‐naïve patients (P = .018). Median OS was 39.8 months (25.0‐55.1) for early relapse and 61.4 months (47.1‐61.4) for late relapse, but was not reached (NR; 55.6–NR) for ET‐naïve patients (P = .002). Fulvestrant monotherapy as the first ET after MBC diagnosis demonstrates PFS comparable to clinical study results; outcomes appeared better in patients without prior ET exposure and in patients with disease recurrence >12 months following adjuvant ET. These findings support fulvestrant monotherapy in patients with hormone receptor‐positive MBC.     

A Very Short Course of HBIg+NA Followed by Entecavir or Tenofovir Monotherapy Prevents HBV Recurrence in Low-Risk Liver Transplant Recipients

BackgroundMonoprophylaxis with third-generation nucleos(t)ide analogues (NAs) can be safely adopted in hepatitis B virus (HBV)-positive, liver transplantation (LT) patients after at least 6 months of HBV immunoglobulin (HBIg)+NA. We investigated the efficacy of earlier initiation of post-LT entecavir (ETV) or tenofovir (TDF) monoprophylaxis.MethodsBetween September 2011 and January 2017, all consecutive hepatitis B surface antigen (HBsAg)-positive transplanted patients were scheduled to receive HBIg with ETV or TDF for a period related to the risk for HBV reinfection: 1. low-risk patients (HBeAg-negative and HBV DNA < 12 IU/mL before LT) were due to withdraw from HBIg once HBsAg had become negative after a minimum of 7 days of HBIg+NA; 2. high-risk patients were due to receive HBIg for at least 6 months, after which they continued with third-generation NA monotherapy, only.ResultsTwenty patients with a median interquartile range (IQR) follow-up of 46 (64-39) months were enrolled in the study (40% receiving ETV, 60% receiving TDF). Two low-risk patients refused early HBIg withdrawal and were therefore treated and analyzed along with the high-risk group. Eventually, there were 2 groups: group A, which included 12 low-risk patients, and group B, which included 8 patients (six high-risk, 2 low-risk). After transplantation, group A and B patients received HBIg+NA for a median (IQR) time of 7 (9-7) days and 9 (13-5) months, respectively. All 20 recipients demonstrated HBV DNA < 12 IU/mL and stable graft function during follow-up. Two patients (10%), 1 from each group, had HBsAg relapse. Notably, both patients who relapsed had hepatocellular carcinoma (HCC) diagnosed before LT and showed very low levels (< 0.25 IU/mL) of HBsAg after recurrence.ConclusionIn low-risk HBsAg-positive recipients, HBIg may be safely discontinued within 2 weeks of LT and replaced by ETV or TDF monotherapy.     

Prophylactic use of low-dose, on-demand, intramuscular hepatitis B immunoglobulin and lamivudine after liver transplantation

The combination of hepatitis B immunoglobulin (HBIG) and antivirals (nucleos[t]ide analogs) has extended the applicability of orthotopic liver transplantation (OLT) for patients with hepatitis B virus (HBV)-related liver disease. However, HBIG administrations have an extremely high cost. Herein, we evaluated our results with low-dose, on-demand, intramuscular HBIG plus lamivudine (LAM) prophylaxis after OLT. The HBV DNA status in 40 patients at the time of OLT determined the treatment: group A (n = 22), HBV DNA (-), no antiviral pretreatment; group B (n = 11), HBV DNA (-), after LAM; group C (n = 3), HBV DNA (+) after LAM (LAM resistance/Adefovir [ADV] unavailable); group D (n = 2), HBV DNA (+), no antiviral pretreatment; and group E (n = 2), HBV DNA (-) after LAM + ADV (LAM resistance/ADV available). Five patients died within 12 months after OLT unrelated to HBV infection. The remaining 35 patients were followed for a median duration of 16 months (range, 6-93 months). Only two recipients from group C, who were transplanted despite LAM resistance + no ADV pretreatment, revealed recurrent HBV infections at 14 and 16 months posttransplantation; they were then treated successfully with ADV as it became available. The third group C recipient had undetectable HBV DNA at 18 months after OLT. The mean cumulative doses of HBIG administered within the first, second, and third years were 34,014, 5258, and 5090 IU, respectively. In conclusion, low-dose, on-demand, intramuscular HBIG plus (LAM +/- ADV) prophylaxis is a safe, efficient, and cost-effective regimen to prevent recurrent HBV infection following OLT. OLT despite untreated LAM resistance may require sustained higher serum HBsAb levels after surgery.     

阿德福韦酯初治耐药与阿德福韦酯挽救治疗再耐药患者的临床特征比较

目的：研究阿德福韦酯（ADV）初治耐药和ADV挽救治疗拉米夫定（LAM）耐药者再耐药的临床和病毒学特点。方法对ADV治疗过程中出现病毒突破的患者进行耐药位点的检测。明确耐药位点患者中单用ADV者37例,LAM耐药后换用ADV的患者40例,患者发生病毒学突破时留取血清标本,行血生化检测并收集其临床资料。结果 ADV初治耐药（ADVr）组和ADV挽救LAM耐药再耐药（LAMr/ADVr）组患者临床特征中的平均年龄、性别分布、HBsAg定量、HBV DNA载量、基因型分布、肝功能指标（TBil、ALT和AST水平）等差异均无统计学意义（P均＞0.05）,但两组患者的HBeAg阳性率差异具有统计学意义（57.5%vs 83.8%;χ^2=6.339,P=0.012）。在病毒学特征方面,N236T变异、A181T＋N236T变异更多发生于ADVr组患者中,而LAMr/ADVr组患者的耐药模式更加复杂。结论 LAM耐药后换用ADV治疗同样会导致病毒耐药的发生,临床特征和ADV初治耐药相近,但引起HBV变异模式的复杂化。     

抗HBV-树突状细胞联合恩替卡韦治疗慢性乙型肝炎疗效观察

目的：观察HBsAg致敏自体外周血单个核细胞（PBMC）来源的树突状细胞（抗HBV-DCs）联合恩替卡韦对慢性乙型肝炎（CHB）的治疗效果。方法104例CHB患者随机分成治疗组（抗HBV-DCs联合恩替卡韦治疗,51例）和对照组（恩替卡韦治疗,53例）,比较患者肝功能、HBV DNA、HBeAg的变化。结果治疗组HBV DNA低于检测下限的比率与对照组差异无统计学意义（P ＞0.05）,但治疗组HBeAg阴转率（35.3%）、HBeAg血清学转换率（31.4%）以及ALT复常率（84.3%）均显著高于对照组（分别为22.6%、17.0%及71.7%）,治疗组治疗6个月时,其HBV DNA低于检测下限的比率（66.7%）、HBeAg转阴率（35.3%）、HBeAg血清学转换率（31.4%）以及ALT复常率（84.3%）均显著高于治疗3个月时（分别为35.3%、19.6%、11.8%及68.6%）,差异均具有统计学意义（P ＜0.05）。结论抗HBV-DCs联合恩替卡韦治疗CHB较单用恩替卡韦疗效更佳。     

A randomized,controlled clinical trial to evaluate the immunogenicity of a PreS/S hepatitis B vaccine Sci-B-Vac™, as compared to Engerix B<Superscript>®</Superscript>, among vaccine naïve and vaccine non-responder dialysis patients

Background

Dialysis patients have a suboptimal response to hepatitis B (HBV) vaccination. This study aimed to compare the immunogenicity of two vaccines: the third-generation Sci-B-Vac? vs. the second-generation Engerix B^®. The cohort included two groups of dialysis patients: naïve and previously vaccinated non-responders. Primary endpoints were antibody titers ≥10 IU/L at 3 and 7 month post-vaccination. Secondary objectives were seroprotection rates in vaccine-naïve patients and in previously vaccinated non-responders.

Methods

Eighty-six patients were assigned to vaccine (Sci-B-Vac? or Engerix B^®) using computer-generated randomization, stratified by age, gender, diabetes, and previous HBV vaccination. Sci-B-Vac? was administered in three doses, 10 μg, at 0, 1, and 6 months in naïve patients; or 20 μg in previously vaccinated non-responders. Engerix B^® included four doses, 40 μg at 0, 1, 2, and 6 months.

Results

Each group had 43 patients. Seroconversion was 69.8% with Engerix B^® vs. 73.2% with Sci-B-Vac?. Antibody titers at 7 months were higher with Sci-B-Vac? (266.4 ± 383.9, median 53.4) than with Engerix^® (193.2 ± 328.9, median 19). However, these differences were not significant, perhaps due to a suboptimal sample size.

Conclusions

This study suggests comparable immunogenicity for both vaccines. Thus, we cannot reject the null hypothesis that there is no difference in seroconversion by vaccine type. It is noteworthy that naïve patients were vaccinated with a standard dose of Sci-B-Vac?, while Engerix B^® was administered at a double dose. Similarly, although mean antibody titer levels in the Sci-B-Vac? group were higher than in the Engerix^® group, this difference did not reach significance. Consequently, a future clinical trial should recruit a larger cohort of patients, using a standard double-dose protocol in both groups.

     

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。