Marzano Alfredo, Lampertico Pietro, Mazzaferro Vincenzo, Carenzi Silvia, Vigano Mauro, Romito Raffaele, Pulvirenti Andrea, Franchello Alessandro, Colombo Massimo, Salizzoni Mauro, Rizzetto Mario
Department of Gastroenterology, San Giovanni Battista Hospital, Turin, Italy.
Liver Transpl. 2005 May;11(5):532-8. doi: 10.1002/lt.20393.
The combination of lamivudine and hepatitis B immunoglobulin (HBIG) reduces the risk of hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, the efficacy of this strategy and the need for combined therapy with adefovir dipivoxil (ADV) in patients who select lamivudine-resistant strains (YMDD) before surgery is still unknown. Twenty-two patients treated with lamivudine (LAM) who underwent LT after YMDD-mutant selection were studied. In 13 patients, YMDD mutants were associated with an HBV DNA breakthrough greater than 5 log10 (group A: phenotypic resistance), and 11 were treated with ADV to decrease viral load before LT. In the remaining 9 patients who did not experience the viral breakthrough, YMDD mutants were detected only retrospectively in sera stored at the time of LT (group B: genotypic resistance). During 35 months of post-LT follow-up, none of the 11 patients of group A treated with ADV before and after surgery (in addition to HBIG and LAM) had HBV recurrence, and neither did any of the 7 subjects of group B treated with LAM before and after transplantation (in addition to HBIG). HBV recurred in 2 patients of group A (untreated with ADV before surgery and transplanted with an HBV DNA exceeding 5 log10) and in 2 subjects of group B (who spontaneously stopped HBIG after surgery). In carriers of YMDD mutants, the risk of post-LT HBV recurrence is low, provided that preemptive and prophylactic ADV (in addition to LAM and HBIG) treatment is used in highly viremic patients and prophylactic LAM (or ADV) and HBIG therapy is continued in low viremic patients.
拉米夫定与乙型肝炎免疫球蛋白(HBIG)联合使用可降低肝移植(LT)后乙型肝炎病毒(HBV)复发的风险。然而,该策略的疗效以及术前选择拉米夫定耐药株(YMDD)的患者联合使用阿德福韦酯(ADV)进行治疗的必要性仍不明确。对22例在选择YMDD突变体后接受LT的拉米夫定(LAM)治疗患者进行了研究。13例患者中,YMDD突变体与HBV DNA突破大于5 log10相关(A组:表型耐药),11例在LT前接受ADV治疗以降低病毒载量。其余9例未发生病毒突破的患者中,仅在LT时储存的血清中回顾性检测到YMDD突变体(B组:基因型耐药)。在LT后的35个月随访中,A组11例术前和术后接受ADV治疗(除HBIG和LAM外)的患者均未发生HBV复发,移植前后接受LAM治疗(除HBIG外)的B组7例患者也均未复发。A组2例患者(术前未接受ADV治疗且移植时HBV DNA超过5 log10)和B组2例患者(术后自行停用HBIG)发生了HBV复发。在YMDD突变体携带者中,LT后HBV复发的风险较低,前提是对高病毒血症患者采用抢先和预防性ADV治疗(除LAM和HBIG外),对低病毒血症患者继续采用预防性LAM(或ADV)和HBIG治疗。