Hepatitis B: Progress in the last 15 years

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Liver Transplantation

October 2002, Supplement 1 . Volume 8 . Number 10


Session III-Hepatitis B

Hepatitis B: Progress in the last 15 years

Abstract
1. Patients undergoing orthotopic liver transplantation (OLT) for hepatitis
B without effective prophylaxis have a high risk for recurrent infection and
severe graft damage, leading to death or re-OLT.
2. Long-term prophylaxis with hepatitis B immune globulin (HBIg)
significantly reduces the risk for hepatitis B virus (HBV) recurrence and
increases survival. Patients with detectable HBV DNA at the time of OLT have a high risk for recurrence despite HBIg prophylaxis.
3. Lamivudine (LAM) therapy for patients with decompensated HBV cirrhosis before OLT results in inhibition of viral replication and clinical
improvement. Its efficacy is limited by the frequent emergence of
LAM-resistant YMDD mutations. The ideal length of therapy with LAM pre-OLT has not yet been defined.
4. Prophylaxis of HBV recurrence with LAM monotherapy is not recommended because of the reappearance of hepatitis B surface antigen after OLT in approximately 50% of patients.
5. LAM is the best available treatment for patients with established
recurrent hepatitis B. Long-term therapy is associated with the emergence of drug-resistant mutants in up to 60% of patients. Severe hepatitis and liver failure have been described among liver transplant recipients with YMDD mutations.
6. Combination therapy with HBIg and LAM prevents HBV recurrence in 90% to 100% of patients who undergo OLT for hepatitis B. The optimal HBIg protocol in the LAM era is yet to be defined.
7. Preliminary studies suggest that adefovir dipivoxil inhibits HBV
replication in patients infected with LAM-resistant HBV strains.
8. Fifteen years ago, hepatitis B was regarded as a relative or absolute
contraindication for OLT. Today, hepatitis B is a universally accepted
indication for OLT. (Liver Transpl 2002;8:S59-S66.)

Publishing and Reprint Information

From the Hepatology and Liver Transplantation Unit, Fundacion Favaloro,
Buenos Aires, Argentina.

Address reprint requests to Federico G. Villamil, MD, Hepatology and Liver
Transplantation Unit, Fundacion Favaloro, Buenos Aires, Argentina.
Telephone: 54-11-4378-1366; FAX: 54-11-4378-1392; E-mail:
[email protected]

Copyright © 2002 by the American Association for the Study of Liver Diseases

1527-6465/02/0810-1003$35.00/0

doi:10.1053/jlts.2002.35782

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我试试翻译如下：
Hepatitis B: Progress in the last 15 years
Liver Transplantation

October 2002, Supplement 1 . Volume 8 . Number 10


Session III-Hepatitis B

Hepatitis B: Progress in the last 15 years

乙肝专题： 肝移植最近15年进展。
2002年10月 第八卷，第10期，附录1

乙肝第三部分，关于最近的15年肝移植进展

Abstract
1. Patients undergoing orthotopic liver transplantation (OLT) for hepatitis
B without effective prophylaxis have a high risk for recurrent infection and
severe graft damage, leading to death or re-OLT.
2. Long-term prophylaxis with hepatitis B immune globulin (HBIg)
significantly reduces the risk for hepatitis B virus (HBV) recurrence and
increases survival. Patients with detectable HBV DNA at the time of OLT have a high risk for recurrence despite HBIg prophylaxis.
摘要：
1。因HBV原因接受原位肝移植（OLC）的病人，如果没有得到有效的预防，那么他们再次感染的可能性很大，并且会引起严重的肝移植破坏，导致死亡或重新接受原位肝移植手术；
2 长期使用HBV免疫球蛋白（HBIG），可以减少再次感染HBV的危险性，延长存活期；HBVDNA阳性的病人，不管是否使用免疫球蛋白，在此时期接受原位肝移植后再次感染的可能性较大；

3. Lamivudine (LAM) therapy for patients with decompensated HBV cirrhosis before OLT results in inhibition of viral replication and clinical
improvement. Its efficacy is limited by the frequent emergence of
LAM-resistant YMDD mutations. The ideal length of therapy with LAM pre-OLT has not yet been defined.
4. Prophylaxis of HBV recurrence with LAM monotherapy is not recommended because of the reappearance of hepatitis B surface antigen after OLT in approximately 50% of patients.
3。对于代谢失调的肝硬化病人，在接受原位肝移植之前，使用拉米可有助于抑制病毒复制，提高临床的效果。
4。不推荐单独使用拉米，因为在接受原位肝移植后，大约有50%的病人被检测出HBV表面抗原阳性；
5. LAM is the best available treatment for patients with established
recurrent hepatitis B. Long-term therapy is associated with the emergence of drug-resistant mutants in up to 60% of patients. Severe hepatitis and liver failure have been described among liver transplant recipients with YMDD mutations.
6. Combination therapy with HBIg and LAM prevents HBV recurrence in 90% to 100% of patients who undergo OLT for hepatitis B. The optimal HBIg protocol in the LAM era is yet to be defined.
5。对于再次感染HBV的病人，拉米是一种比较好的药物；但长期使用拉米治疗会导致产生抗药性的突变异种，比例高达60%；，在肝移植的病例中，肝炎严重和肝功能衰竭病人中发现YMDD突变。
6。使用免疫球蛋白 和拉米联合治疗，有助于防止接受OLT治疗的HBV病人再次感染HBV，有效率达90%-100%，在拉米时代，最佳的免疫球蛋白协议还未确定；
7. Preliminary studies suggest that adefovir dipivoxil inhibits HBV
replication in patients infected with LAM-resistant HBV strains.
8. Fifteen years ago, hepatitis B was regarded as a relative or absolute
contraindication for OLT. Today, hepatitis B is a universally accepted
indication for OLT. (Liver Transpl 2002;8:SS59-S66.)
7。初步研究表明，对于感染抗拉米的HBV病人，阿德福韦有助于抑制HBV的复制；
8。15年前，对OLT来说，HBV是绝对或相对的禁忌候症；今天，HBV已经被广泛接受可以实施OLT。（肝移植，2002；8：S59-S66。）
Publishing and Reprint Information
出版和复印信息（以下翻译略）
From the Hepatology and Liver Transplantation Unit, Fundacion Favaloro,
Buenos Aires, Argentina.

Address reprint requests to Federico G. Villamil, MD, Hepatology and Liver
Transplantation Unit, Fundacion Favaloro, Buenos Aires, Argentina.
Telephone: 54-11-4378-1366; FAX: 54-11-4378-1392; E-mail:
[email protected]

Copyright © 2002 by the American Association for the Study of Liver Diseases

1527-6465/02/0810-1003$35.00/0

doi:10.1053/jlts.2002.35782

龙漂飘

阿德福韦
学科分类：调节免疫功能药物
通用名称：阿德福韦/adefovir dipivoxil
生产厂商：Gilead Sciences
药理作用：核苷类抗病毒药，也属逆转录酶抑制剂

适 应 症：乙肝。抑制对拉米夫定产生抗药性的乙肝病毒。
    2001年该药正处于III期临床试验，尚未正式生产和销售。 Adefovir Dipivoxil最初也是用于对爱滋病的治疗。在治疗慢性乙肝时，其药量是治疗HIV（爱滋病毒）感染的10%到25%，在目前的实验中为10-30毫克/日。在迄今为止的实验中，Adefovir Dipivoxil显示了较小的毒副作用。 目前的临床实验剂量为（每日一次）30毫克（11名患者）及10毫克（12名患者）。 在观察期间，没有病人因副作用而终止Adefovir Dipivoxil的治疗。但有9人因肌酐水平上升而减少了剂量：这其中6人曾做过肝移植，2人已经处于失代偿期，另1人则因要做肝移植而降低白细胞，从而减少了剂量。有两人死亡，但均与Adefovir Dipivoxil无关。 主持这项实验的医生认为，在这段观察时期，Adefovir Dipivoxil使对拉米夫定产生抗药性的乙肝病毒产生了快速而持久的作用，显著改善了患者的肝功能，且在15个月的治疗中显示了良好的耐受性。 目前，一项有695名慢性乙肝患者参加的第3阶段实验正在进行。另一项有130名拉米夫定治疗效果不明显的患者参加的双盲随机研究也在进行之中，参加者将每日服用10毫克Adefovir Dipivoxil及100毫克拉米夫定。 Adefovir Dipivoxil 为对拉米夫定产生抗药性的慢性乙肝患者带来希望。但在对HIV感染患者的治疗中发现，该药在大剂量（每日100--130毫克）服用时会产生明显的肾毒性。