Seehofer D, Rayes N, Bechstein W O, Naumann U, Neuhaus R, Berg T, Hopf U, Langrehr J M, Steinmüller T, Platz K P, Müller A R, Neuhaus P
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Humboldt-Universität zu Berlin.
Z Gastroenterol. 2000 Sep;38(9):773-83. doi: 10.1055/s-2000-7528.
Before introduction of passive immunoprophylaxis and new antiviral nucleoside analogues the course of hepatitis B recurrence after liver transplantation could hardly be influenced. The result was a inferior graft survival. In the present retrospective analysis of the efficacy of hepatitis B therapy after liver transplantation was analysed retrospectively.
Between 1988 and 1998 in total 179 patients were transplanted due to hepatitis B related liver failure at our centre. All patients received passive immunoprophylaxis with hepatitis B immunoglobulin. In case of reinfection after 1993 an antiviral therapy with famciclovir 1500 mg daily was initiated (n = 26), since 1996 lamivudine (100-150 mg daily) was used (n = 12). In case of viral breakthrough under famciclovir treatment or prophylaxis therapy was switched to lamivudine (n = 22). In case of ineffectiveness of lamivudine an antiviral combination therapy with lamivudine and interferon (n = 4) or lamivudine and famciclovir (n = 4) was initiated. Before availability of antiviral agents or in case of viral breakthrough in total 12 patients were retransplanted due to acute or chronic reinfection.
With passive immunoprophylaxis reinfection rate was 33%, 43% and 44% after 1, 3 and 5 years respectively. Without antiviral treatment 52% of patients died within the first year after reinfection. Antiviral therapy with lamivudine or famciclovir improved the one year survival after reinfection to 79%. Suppression of viral replication was more effective with lamivudine. Under lamivudine 26 patients (76%) became HBV-DNA negative, 9 patients HBsAg negative (26%). In contrast no patient became HBsAg negative during famciclovir therapy. Lamivudine was effective also after famciclovir breakthrough in 94% of patients. In case of lamivudine resistant reinfection viral replication could be suppressed with an antiviral combination therapy up to negative HBV-DNA in the hybridization assay. Severe side effects were not observed during any of the antiviral therapies. The graft survival after retransplantation for hepatitis B reinfection was 42% and 25% after one and 3 years.
Whereas it is generally accepted, that passive immunoprophylaxis lowers the reinfection rate it could be shown in the present study, that antiviral treatment lowers mortality of hepatitis B reinfection. The major problem of lamivudine and famciclovir is viral resistance formation. In this case an antiviral combination therapy might be useful, whereas retransplantation for hepatitis B reinfection should be considered carefully due to inferior graft survival rates.
在被动免疫预防和新型抗病毒核苷类似物出现之前，肝移植后乙肝复发的病程几乎无法得到控制，导致移植肝存活率较低。本研究对肝移植后乙肝治疗的疗效进行了回顾性分析。
1988年至1998年间，本中心共有179例因乙肝相关肝衰竭接受肝移植的患者。所有患者均接受乙肝免疫球蛋白被动免疫预防。1993年后若发生再感染，则开始使用泛昔洛韦每日1500mg进行抗病毒治疗（n = 26），自1996年起使用拉米夫定（每日100 - 150mg）（n = 12）。若在泛昔洛韦治疗期间出现病毒突破，则将预防治疗改为拉米夫定（n = 22）。若拉米夫定治疗无效，则开始使用拉米夫定与干扰素联合抗病毒治疗（n = 4）或拉米夫定与泛昔洛韦联合抗病毒治疗（n = 4）。在抗病毒药物可用之前或因急性或慢性再感染导致病毒突破的情况下，共有12例患者接受了再次肝移植。
采用被动免疫预防，1年、3年和5年后的再感染率分别为33%、43%和44%。未进行抗病毒治疗时，52%的患者在再感染后的第一年内死亡。使用拉米夫定或泛昔洛韦进行抗病毒治疗可将再感染后的1年生存率提高至79%。拉米夫定对病毒复制的抑制效果更佳。在拉米夫定治疗下，26例患者（76%）的乙肝病毒脱氧核糖核酸（HBV - DNA）转阴，9例患者的乙肝表面抗原（HBsAg）转阴（26%）。相比之下，在泛昔洛韦治疗期间无患者的HBsAg转阴。拉米夫定在泛昔洛韦治疗出现突破后，对94%的患者仍有效。对于拉米夫定耐药的再感染，联合抗病毒治疗可将病毒复制抑制至杂交试验中HBV - DNA阴性。在任何抗病毒治疗过程中均未观察到严重的副作用。因乙肝再感染接受再次肝移植后，1年和3年后的移植肝存活率分别为42%和25%。
尽管普遍认为被动免疫预防可降低再感染率，但本研究表明，抗病毒治疗可降低乙肝再感染的死亡率。拉米夫定和泛昔洛韦的主要问题是形成病毒耐药性。在这种情况下，联合抗病毒治疗可能有用，而因移植肝存活率较低，对于乙肝再感染的再次肝移植应谨慎考虑。
