Fontana R J, Hann H W, Wright T, Everson G, Baker A, Schiff E R, Riely C, Anschuetz G, Riker-Hopkins M, Brown N
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0362, USA.
Liver Transpl. 2001 Jun;7(6):504-10. doi: 10.1053/jlts.2001.24896.
Hepatitis B virus (HBV) infection after liver transplantation (LT) may lead to severe and rapidly progressive graft failure. Antiviral treatment may be of benefit in selected patients with recurrent hepatitis B post-LT. The aim of this prospective open-label study is to determine the safety and efficacy of lamivudine in 33 liver transplant recipients with active HBV infection. The median time from LT to study enrollment was 51 months, all patients were hepatitis B surface antigen positive, and 75% and 94% of subjects had detectable hepatitis B e antigen (HBeAg) and HBV DNA at entry, respectively. The median duration of lamivudine treatment on study was 85 weeks, during which time median HBV DNA levels became undetectable by 16 weeks and 9% of patients lost previously detectable HBeAg. Serum alanine aminotransferase (ALT) levels improved in most patients and normalized in 27% of patients with elevated values pretreatment. Serum bilirubin and albumin levels significantly improved in patients with abnormal values at entry (P <.05). Virological breakthrough was detected in 13 subjects after a median of 61 weeks of lamivudine treatment and was confirmed to be caused by YMDD mutants in all patients tested. None of the patients with virological breakthrough showed a complete loss of clinical response to lamivudine. Serum ALT and bilirubin levels in patients with and without virological breakthrough were not significantly different at last study follow-up. Study results show that lamivudine is safe and effective in liver transplant recipients with recurrent hepatitis B. However, the high rate of virological breakthrough with prolonged therapy indicates the need for further studies of combination antiviral therapy in this patient population. Our results and others further establish the improving long-term outcomes with LT for patients with hepatitis B through advances in prevention of reinfection, as well as the availability of safe and effective antiviral therapies to treat patients with HBV recurrence.
肝移植（LT）后感染乙型肝炎病毒（HBV）可能导致严重且进展迅速的移植物功能衰竭。抗病毒治疗可能对部分肝移植术后乙型肝炎复发的患者有益。这项前瞻性开放标签研究的目的是确定拉米夫定对33例活动性HBV感染的肝移植受者的安全性和疗效。从肝移植到纳入研究的中位时间为51个月，所有患者乙型肝炎表面抗原均为阳性，75%和94%的受试者在入组时可检测到乙型肝炎e抗原（HBeAg）和HBV DNA。研究中拉米夫定治疗的中位持续时间为85周，在此期间，中位HBV DNA水平在16周时变得无法检测到，9%的患者先前可检测到的HBeAg消失。大多数患者血清丙氨酸氨基转移酶（ALT）水平有所改善，27%治疗前ALT值升高的患者恢复正常。入组时血清胆红素和白蛋白水平异常的患者这些指标显著改善（P<0.05）。在拉米夫定治疗中位61周后，13例受试者检测到病毒学突破，所有检测患者均证实由YMDD突变引起。病毒学突破的患者中无一例显示对拉米夫定的临床反应完全丧失。在最后一次研究随访时，有和没有病毒学突破的患者血清ALT和胆红素水平无显著差异。研究结果表明，拉米夫定对肝移植术后乙型肝炎复发的患者安全有效。然而，长期治疗时病毒学突破发生率高表明需要对该患者群体的联合抗病毒治疗进行进一步研究。我们的结果以及其他研究结果进一步证实，通过预防再感染方面的进展以及有安全有效的抗病毒疗法来治疗HBV复发患者，肝移植可改善乙型肝炎患者的长期预后。
