抗乙肝的Tx驱动器的变化肝移植

StephenW

Anti-Hep B Tx Drives Changes in Liver Transplantation

    by Scott Harris
    Contributing Writer, MedPage Today

Action Points

    Powerful anti-hepatitis B virus drugs can potentially decrease the recurrence of the HBV in liver transplant patients, and even lower the number of transplants that result from complications related to HBV.
    Note that the patients who developed breakthrough hepatitis B infection improved after they were switched from monotherapy to a different oral agent or a combination of agents.

Powerful anti-hepatitis B virus (HBV) drugs can potentially decrease the recurrence of the HBV in liver transplant patients, and even lower the number of transplants that result from complications related to HBV, according to a retrospective study.

After a median follow-up of 82 months, the rate of post-liver transplant survival was 89% and the rate of HBV recurrence was 11% in over 100 patients, reported Waleed Al-Hamoudi, MD, of King Saud University College of Medicine in Riyadh, and colleagues.


In addition, from 2001 to 2006, 50% of the liver transplants performed at the center were caused by cirrhosis induced by the hepatitis C virus, while 17% of the transplants were caused by HBV-induced cirrhosis, and 12% by nonalcoholic steatohepatitis-related cirrhosis (NASH), they wrote in the World Journal of Gastroenterology.

From January 2007 to January 2012, HBV fell behind NASH to become the third-leading indication for liver transplant, with 16% of all cases, they added.

"The use of highly potent anti-hepatitis B virus agents has led to adequate control of viral replication, significant biochemical remission, histological improvement, and the prevention of hepatic decompensation," they explained. "These effects are expected to subsequently result in a reduction in the rate of hepatitis B virus-related liver transplantation."

The study included data from 133 patients who underwent liver transplants for HBV-related cirrhosis at Saudi Arabia's King Faisal Specialist Hospital and Research Center from 1990 to 2012.

The majority of the patients were treated with HBV immune globulin and at least one nucleos(t)ide analog drug, such as lamivudine (Epivir), adefovir (Hepsera), entecavir (Baraclude), or tenofovir (Viread). The immune globulin was administered intravenously at a dose of 10,000 units during the anhepatic phase and 5,000 units daily during the first week, with an ultimate target being an HBV surface antibody titer of >500 IU/mL.

The authors reported that patients who were positive for the HBV antigen before a liver transplant were more likely to experience recurrence versus those who tested negative for the antigen (OR=9.6, 95% CI 2.99 to 30.85, P<0.0001). Patients with positive HBV DNA levels before a transplant were almost four times as likely to experience a recurrence than those who did not (OR=4.1, 95% CI 1.08 to 15.5, P=0.04), according to the study.

"The availability of a newer generation of nucleos(t)ide analogs has resulted in a significant improvement in the outcome of liver transplantation for hepatitis B virus-related liver disease," the authors wrote. "Controlling viral replication ... will improve transplantation outcomes."

Among pretransplant patients, the majority (61%) took lamivudine, followed by a combination of lamivudine and adefovir (15%). The disease recurred in only 15 patients (11%) after transplantation.

The 15 patients who developed breakthrough hepatitis B infection -- defined in the study as a "re-emergence of hepatitis B virus DNA or hepatitis B surface antigen" -- improved after they were switched from monotherapy to a different oral agent or a combination of agents.

"The development of potent hepatitis B virus drugs with high genetic barriers to resistance has resulted in significant suppression of viral replication," the authors wrote. "As a result, overall patient survival has improved due to the prevention of disease progression to cirrhosis ...The decline in hepatitis B-related liver disease as an indication for liver transplantation is likely related both to the various mass screening programs ... and to the introduction of effective antiviral treatment."

Furthermore, 71 of 96 patients treated with tenofovir experienced a regression of their cirrhosis, which was confirmed through paired biopsies after 5 years.

"This finding could be related to improvements in the control of viral replication with potent medications (entecavir and tenofovir), which has prevented the progression of liver disease to more advanced stages of fibrosis and has prevented decompensation in already cirrhotic patients," they stated.

The study had some limitations including its retrospective design. Also, HBV immunoprophylaxis during the posttransplant follow-up period was not consistent for all patients, and data on pretransplantation HBV DNA status, pretransplantation HBV serological markers, and HDV coinfection were not available for some of the participants.

StephenW

抗乙肝的Tx驱动器的变化肝移植

    由斯科特·哈里斯
    特约撰稿人，MedPage今天

行动要点

    强大的抗乙肝病毒药物可以潜在地减少在肝移植患者的HBV的复发，并且甚至降低所造成的相关的HBV并发症移植的数量。
    需要注意的是谁开发，他们从单一疗法被切换到不同的口服药物或药物组合后突破乙肝感染者改善了病人。

强大的抗乙肝病毒（HBV）的药物可潜在降低在肝移植患者的HBV的复发，并且甚至降低所造成的相关的HBV并发症移植的数量，根据回顾性研究。

在平均随访82个月后肝移植存活率的比率为89％和乙肝复发率为11％，在100例患者，报道瓦利德 - Hamoudi医学沙特国王大学，医学博士，在利雅得，和同事。


此外，从2001年到2006年，在该中心进行肝脏移植的50％是由肝硬化引起的丙型肝炎病毒引起的，而移植的17％是由HBV引起的肝硬化引起的，并且由无酒精steatohepatitis- 12％相关性肝硬化（NASH），它们在胃肠病学世界日报写道。

从2007年1月至2012年1月，HBV落后纳什成为第三领先的适应症肝移植，与所有案件的16％，他们补充说。

“使用高度有效的抗乙型肝炎病毒剂导致了病毒复制，显著生化缓解，组织学改善和预防肝功能失代偿的适当控制，”他们解释。 “这些效应预计将随后导致乙型肝炎病毒相关的肝移植的速率减少。”

该研究共纳入133例患者谁接受肝脏移植手术的HBV相关性肝硬化在沙特的费萨尔国王专科医院和研究中心1990年至2012年的数据。

大部分的患者进行治疗乙肝免疫球蛋白和至少一种核苷（酸）IDE模拟药物，如拉米夫定（拉米），阿德福韦（Hepsera治疗），恩替卡韦（博路定），或者替诺福韦（Viread的）。免疫球蛋白静脉注射，在第一周的剂量在无肝期10000台和5000台每天，有一个最终的目标是> 500 IU / ml的乙肝病毒表面抗体滴度。

作者报告说谁是阳性的肝脏移植前的HBV抗原患者更容易出现复发与那些谁（到30.85，P <0.0001 OR = 9.6，95％CI为2.99），未检测出抗原。患者移植前HBV DNA阳性水平的可能性几乎是四倍体验复发谁比那些没有（OR = 4.1，95％CI为1.08〜15.5，P = 0.04），根据这项研究。

“更新一代的核苷（酸）类似物的可用性导致了肝移植乙肝病毒相关性肝病的结果的显著的改善，”作者写道。 “控制病毒复制...会提高移植成果。”

间移植前患者中，大多数（61％）注意到拉米夫定，随后拉米夫定和阿德福韦（15％）的组合。该疾病复发移植后仅15名患者（11％）。

谁开发突破性的乙肝感染的15例患者 - 在研究中定义为“重新出现乙肝病毒DNA或乙型肝炎表面抗原” - 他们从单一被切换到不同的口服药物或组合后好转代理。

“强效乙型肝炎病毒药物具有高耐药基因屏障的发展已经导致了病毒复制显著的抑制，”作者写道。 “这样一来，患者总体生存期已因病情恶化的预防肝硬化提高......在乙肝相关肝病的指示肝移植的下降很可能与双方的各种大规模​​筛查项目...并采用有效抗病毒治疗。“

此外，96例替诺福韦治疗的71经历了肝硬化，它通过配对活检5年后证实的回归。

“这一发现可能与改进病毒复制具有强效药物（恩替卡​​韦和替诺福韦），它防止了肝脏疾病的进展到纤维化更晚期阶段，并防止失代偿在已经肝硬化患者的控制”，他们指出。

该研究有一些限制，包括它的回顾性设计。此外，在移植后随访乙肝免疫预防是不是对所有患者一致，并在移植前HBV DNA状态，移植前HBV血清学标志和HDV合并感染的数据是不适合某些参与者。