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肝炎病毒与肝移植

Hepatitis viruses and liver transplantation.

作者信息

Samuel D, Feray C, Bismuth H

机构信息

Hepatobiliary Center, Paris South University, Hôpital Paul Brousse, Villejuif, France.

出版信息

J Gastroenterol Hepatol. 1997 Oct;12(9-10):S335-41. doi: 10.1111/j.1440-1746.1997.tb00518.x.

DOI:10.1111/j.1440-1746.1997.tb00518.x
PMID:9407355
Abstract

Acute and chronic liver diseases related to hepatitis viruses are the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. The risk of viral B reinfection is: 80% in the absence of prophylaxis; is related to the presence of active viral B replication prior to transplantation; is higher in patients with chronic liver disease, rather than with fulminant hepatitis; and is higher in patients with hepatitis B virus (HBV)-related liver disease alone rather than in those with HBV-hepatitis delta virus (HDV) infection. Post-transplant long-term passive antibody to hepatitis B (anti-HB) immunoprophylaxis reduces the risk of HBV recurrence to 30% in patients with HBV cirrhosis, and to less than 10% in those with fulminant hepatitis B. Patients with HBV-HDV liver disease receiving passive anti-HB immunoprophylaxis are at low risk of HBV recurrence (10-15%), but at high risk of HDV recurrence (80%). However, HDV reinfection of the graft has no clinicopathological consequence in the absence of concomitant HBV reinfection. The five year survival of patients transplanted for HBV cirrhosis and for HDV cirrhosis at the Hepatobiliary Center, Hôpital Paul Brousse is 72% and 85%, respectively. Hepatitis B virus reinfection of the graft is characterized by a high level of viral replication, and a chronic outcome. Antiviral treatments such as ganciclovir, adenine arabinoside monophosphate, famcyclovir, and lamivudine have a place after transplantation and may stop HBV replication, ganciclovir, famcyclovir and lamivudine should be continued for several months and in some cases indefinitely. Hepatitis C virus reinfection is almost constant, assessed by the persistence of hepatitis C virus (HCV)-RNA in the serum in 90% of cases. Acute lobular hepatitis appeared in 75% of patients at a median of 4 months post transplantation with a range of between 23 days and 4 years. In our series, the 5 year actuarial rate of HCV acute hepatitis on the graft, chronic hepatitis, and cirrhosis, is 75, 60, and 8%, respectively. Hepatitis C virus RNA level is dramatically increased after transplantation and seems to correlate with the occurrence of acute hepatitis on the graft. A positive relation between genotype 1b and prevalence and severity of HCV hepatitis on the graft have been suggested in European series. There is no demonstrated way to prevent HCV reinfection. The use of interferon for the treatment of HCV hepatitis on the graft was disappointing due to a poor antiviral effect and the occurrence of chronic rejection episodes in some patients. Promising results of the combination of interferon and ribavirine have been reported and need confirmation. The 5 year survival of patients transplanted for viral C cirrhosis at the Hepatobiliary Center, Hôpital Paul Brousse is 78%. In conclusion, patients with HBV cirrhosis and without HBV replication are candidates for liver transplantation. Long-term passive anti-HB prophylaxis is the best way to prevent HBV recurrence. Patients with HBV replication should be included in protocols using combinations of antiviral treatments and passive anti-HB immunoprophylaxis. Viral C reinfection is frequent, but medium-term survival is good. However, long-term graft and patient survival remains unknown and methods to prevent and treat HCV reinfection on the graft are needed.

摘要

与肝炎病毒相关的急慢性肝病是肝移植的主要适应证。移植后病毒再感染的风险是这些适应证的主要限制因素。乙型肝炎病毒(HBV)再感染的风险为:未进行预防时为80%;与移植前HBV活跃复制有关;在慢性肝病患者中高于暴发性肝炎患者;在单纯HBV相关肝病患者中高于HBV-丁型肝炎病毒(HDV)感染患者。移植后长期被动抗乙型肝炎抗体(抗-HB)免疫预防可将HBV肝硬化患者的HBV复发风险降至30%,将暴发性乙型肝炎患者的该风险降至10%以下。接受被动抗-HB免疫预防的HBV-HDV肝病患者HBV复发风险较低(10%-15%),但HDV复发风险较高(80%)。然而,在无伴随HBV再感染的情况下,HDV对移植物的再感染无临床病理后果。保罗·布罗斯医院肝胆中心接受HBV肝硬化和HDV肝硬化移植患者的5年生存率分别为72%和85%。HBV对移植物的再感染以高水平病毒复制和慢性结局为特征。更昔洛韦、单磷酸阿糖腺苷、泛昔洛韦和拉米夫定等抗病毒治疗在移植后有一定作用,可阻止HBV复制,更昔洛韦、泛昔洛韦和拉米夫定应持续使用数月,在某些情况下需无限期使用。丙型肝炎病毒(HCV)再感染几乎是必然的,90%的病例血清中HCV核糖核酸(HCV-RNA)持续存在可证实这一点。75%的患者在移植后中位4个月(范围为23天至4年)出现急性小叶性肝炎。在我们的系列研究中,移植物发生HCV急性肝炎、慢性肝炎和肝硬化的5年精算率分别为75%、60%和8%。移植后HCV-RNA水平显著升高,似乎与移植物急性肝炎的发生相关。欧洲的系列研究提示,1b型基因型与移植物HCV肝炎的发生率和严重程度呈正相关。尚无已证实的预防HCV再感染的方法。由于抗病毒效果不佳且部分患者出现慢性排斥反应,使用干扰素治疗移植物HCV肝炎的结果令人失望。已报道干扰素与利巴韦林联合使用有良好效果,尚需进一步证实。保罗·布罗斯医院肝胆中心接受丙型肝炎肝硬化移植患者的5年生存率为78%。总之,无HBV复制的HBV肝硬化患者是肝移植的候选者。长期被动抗-HB预防是预防HBV复发的最佳方法。有HBV复制的患者应纳入采用抗病毒治疗与被动抗-HB免疫预防联合方案的研究。HCV再感染很常见,但中期生存率良好。然而,移植物和患者的长期生存情况尚不清楚,需要有预防和治疗移植物HCV再感染的方法。

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