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出处：WebMD医学新闻
审阅：Maria L. Gaiso, PhD
May 10, 2006 (维也纳) — 初步研究显示，adefovir dipivoxil可以用在对lamivudine无效的病患和肝脏移植病患，避免再度感染B型肝炎病毒(HBV)；虽然这些发现令人振奋，但专家警告还需要长期的追踪，以确定药物效果。
根据Jean-Michel Pawlotsky医师所述，对肝脏移植者而言，主要的HBV感染风险是HBV复发，而且这种情况下可能特别严重；这可以藉由使用Ｂ型肝炎免疫球蛋白(HBIg)适当地预防，或者并用HBIg和特定抗病毒药物如lamivudine时以达到更好的效果；然而，若病患对lamivudine有抗药性时，以lamivudine治疗则是无用的。
Pawlotsky医师以电子邮件向Medscape表示，新的研究指出，对lamivudine有抗药性的病患（不论有无接受HBIg）在移植前后使用lamivudine加adefovir可以预防HBV感染复发；他并未参与此研究、而是此研究发表时的会议主持人；此研究系由迈阿密大学的Eugene Schiff医师在第41届欧洲肝脏研究学会(EASL)年会发表；Pawlotsky医师是法国国家病毒性肝炎参考数据中心的主任、巴黎第十二大学Henri Mondor医院病毒学系、法国国家卫生及医药研究所U635单位成员，同时也是adefovir制造商Gilead的顾问。
Schiff医师及其同僚对57位有lamivudine抗药性的慢性HBV感染、需要肝脏移植的病患给予adefovir；病患在移植前平均接受该药剂15周、在移植后平均接受该药剂36周，有服用lamivudine者则继续、未予停药，此外、有60%病患接受HBIg。
开始时，所有病患的B肝表面抗原(HBsAg)是阳性，而有42%是B肝e抗原(HbeAg)阳性，病患平均血清HBV DNA 是4.6 log10 copies/mL、平均丙胺酸转胺基酶(ALT)值是1.0 X ULN。
移植后，没有病患是HBsAg阳性且HBV DNA阳性，有4个病患、其中两位有接受HBIg 者在他们移植后的第一次测试中有测到HBsAg，而这两位在后续的检测中变成HbsAg阴性，另两位则没有进行后续追踪。
接受HBIg的病患中，有13%出现一次的HBV DNA比最低定量限度(LLQ)高，在没有接受HBIg的病患中，12%有出现一次的HBV DNA比最低定量限度(LLQ)高。
病患在平均67周的用药中，对adefovir都没有产生抗药性，发生抗药性的累积机率在第96周和第144周是2%。
一般而言，adefovir耐受良好，4位 (7%) 因不良反应停用；在同时使用具肾脏毒性的免疫抑制药物者之中，有84% 的血清肌酸酐是正常的、或者仅是等级1的增加。
作者们在摘要的结论中提到，Adefovir dipivoxil看来不论有无使用HBIg都可以有效预防HBV再度感染，他们也报告此药是对肝脏移植病患安全且一般耐受良好的。
Pawlotsky医师向Medscape表示，此研究显示出这种情况下对有lamivudine抗药性的病患使用adefovir是有好处的；然而，此研究受限于样本数太少，虽然对移植的研究而言57个样本已可算多数。
此外，Pawlotsky医师表示，需要数年的追踪以真实地确认有实际预防HBV感染，并且探究病患发生再度感染的原因，如与抗药性有关、服药顺从性不理想、或者其它原因；他相信未来的研究应该是注重在使用不具抗药性的更有效药物。
Adefovir Dipivoxil May Block Hepatitis B Reinfection in Liver Transplant Patients
By
Medscape Medical News
May 10, 2006 (Vienna) — Early results suggest that adefovir dipivoxil may help block reinfection with the hepatitis B virus (HBV) among infected patients who are resistant to lamivudine and undergo liver transplantation. While these findings are encouraging, an expert warns that long-term follow-up is required to confirm the drug's benefits.
According to Jean-Michel Pawlotsky, MD, PhD, "The principal danger of liver transplantation for HBV infection is HBV recurrence, which may be particularly severe in this context. It is well prevented by the use of hepatitis B immunoglobulins (HBIg), and even [more so] when HBIg are used in combination with specific antivirals such as lamivudine. However, [lamivudine therapy is not helpful] if the patients are already lamivudine resistant."
This new study demonstrates that "using lamivudine plus adefovir in combination in lamivudine-resistant patients prior to and after transplantation prevented HBV infection recurrence in the vast majority of patients, with or without HBIg (ie, it protected the liver graft against HBV)," Dr. Pawlotsky told Medscape via email. He was not involved in the research but was a moderator at the session where it was presented here by Eugene Schiff, MD, from the University of Miami, Florida, at the 41st annual meeting of the European Association for the Study of the Liver (EASL). Dr. Pawlotsky is director of the French National Reference Center for Viral Hepatitis B, C, and delta, Department of Virology and of the INSERM Research Unit U635 at Henri Mondor Hospital, University of Paris 12, in Creteil, France. He is also an advisor for Gilead, the manufacturer of adefovir.
Dr. Schiff and colleagues gave adefovir to 57 patients who had lamivudine-resistant chronic HBV infection and required liver transplantation. Patients received the agent for a median of 15 weeks prior to transplantation and a median of 36 weeks after transplantation. Those initially receiving lamivudine remained on the drug. In addition, 60% of patients received HBIg.
At baseline, all patients were hepatitis B surface antigen (HBsAg)–positive, and 42% were hepatitis B e antigen (HbeAg)–positive. Patients' median serum HBV DNA was 4.6 log10 copies/mL, and their median alanine transaminase (ALT) level was 1.0 X ULN.
After transplantation, none of the patients were both HBsAg-positive and HBV DNA positive. Four patients, 2 of whom received HBIg, had HBsAg detected in their first posttransplantation test. Of these, 2 eventually became HBsAg-negative with subsequent testing, and 2 patients had no additional HBsAg follow-up.
Of the patients who received HBIg, 13% had a single HBV DNA measurement greater than the lower limit of quantification (LLQ). Similarly, among those who did not receive HBIg, 12% had a single HBV DNA measurement over LLQ.
None of the patients developed resistance to adefovir during a mean of 67 weeks on the study drug. Cumulative probabilities of the development of resistance were 2% at weeks 96 and 144.
In general, adefovir was well tolerated. Four patients (7%) discontinued the agent due to adverse events. Of the patients also receiving nephrotoxic immunosuppressant drugs, 84% had normal serum creatinine levels or only grade 1 elevations.
"Adefovir dipivoxil appears to be effective prophylaxis for HBV graft reinfection with or without HBIg," the authors conclude in their abstract. They also reported that the drug is "safe and generally well-tolerated in liver transplantation patients."
Dr. Pawlotsky told Medscape that the study does demonstrate a benefit for using adefovir among lamivudine-resistant patients in this clinical context. The trial, however, is limited by its small sample size, even though a sample of 57 is relatively large for a transplantation study.
In addition, Dr. Pawlotsky said, follow-up of several years is required to truly determine if HBV infection has actually been prevented, whether some patients will experience reinfections, and whether these reinfections are related to resistance, poor adherence, or other causes. He believes that future research should concentrate on use of potent antiviral drugs with good resistance profiles.
EASL 2006: Abstract 2. Presented April 27, 2006.
Reviewed by Maria L. Gaiso, PhD