Caccamo Lucio, Romeo Raffaella, Rossi Giorgio, Maggioni Mauro, Radice Ferdinando, Lunghi Giovanna, Colombo Massimo, Fassati Luigi R
Dipartimento di Chirurgia Generale e dei Trapianti, U.O. Trapianto Fegato e Polmone, Ospedale Maggiore IRCCS di Milano, Istituto di Chirurgia Sperimentale, Cardiovascolare e dei Trapianti, Università degli Studi di Milano, Italy.
Transpl Int. 2005 Feb;18(2):186-92. doi: 10.1111/j.1432-2277.2004.00034.x.
Recurrence of hepatitis B impairs the outcome of liver transplantation (OLT). In serum hepatitis B virus (HBV)-DNA-positive recipients, prophylaxis using lamivudine and immunoglobulins (HBIg) reduces the risk of recurrence, but it is undefined whether this regimen also protects candidates with YMDD mutants. Seventeen OLT viraemic candidates received pre-emptive lamivudine followed by post-OLT prophylaxis with lamivudine and HBIg. Both sera and liver biopsies were prospectively collected and high-sensitive polymerase chain reaction (PCR) assay was applied for HBV-DNA detection. Finally, the presence of YMDD mutants was explored in all PCR-positive samples. All patients remained hepatitis B recurrence-free after a mean follow up of 32 months. By PCR, serum HBV-DNA was detectable in 64.3% of cases at OLT-baseline, in 64.7% under combined prophylaxis and in 58.8% in patients (70.5% of the total) with a minimum follow up of 24 months. At OLT-baseline, YMDD mutants were found in 44.4% of patients. After OLT, mutants were present in 50% of patients but only in 16.6% of cases in the long period. Although 41% of the native livers and 42.8% of the analysed grafts harboured HBV-DNA, YMDD mutants were detected in 57% of the native positive livers. YMDD mutants were largely detected both at OLT-baseline and post-OLT, but their presence decreased over time. Regardless of the presence of YMDD mutants, no hepatitis B recurrence was observed in our OLT recipients using pre-emptive lamivudine followed by continuous prophylaxis with lamivudine and HBIg.
乙型肝炎复发会影响肝移植(OLT)的预后。在血清乙型肝炎病毒(HBV)-DNA阳性的受者中,使用拉米夫定和免疫球蛋白(HBIg)进行预防可降低复发风险,但该方案是否也能保护携带YMDD突变的候选者尚不清楚。17例OLT病毒血症候选者接受了先发制性拉米夫定治疗,随后在OLT后接受拉米夫定和HBIg预防。前瞻性收集血清和肝活检样本,并应用高灵敏度聚合酶链反应(PCR)检测HBV-DNA。最后,在所有PCR阳性样本中检测YMDD突变的存在。所有患者在平均随访32个月后均未出现乙型肝炎复发。通过PCR检测,OLT基线时64.3%的病例血清HBV-DNA可检测到,联合预防时为64.7%,在至少随访24个月的患者(占总数的70.5%)中为58.8%。在OLT基线时,44.4%的患者发现有YMDD突变。OLT后,50%的患者存在突变,但长期来看仅1 / 6的病例存在突变。尽管41%的原肝和42.8%的分析移植物中含有HBV-DNA,但在57%的原肝阳性样本中检测到YMDD突变。YMDD突变在OLT基线和OLT后均大量检测到,但其存在随时间减少。无论是否存在YMDD突变,在我们的OLT受者中,先发制性使用拉米夫定,随后持续使用拉米夫定和HBIg进行预防,均未观察到乙型肝炎复发。