Joh J W, Lee H H, Park J W, Lee D H, Yoo B C, Lee K W, Kim S J
Digestive Disease Research Center, and Department of Internal Medicine and Surgery, Samsung Medical Center, SungKyunKwan University School of Medicine, Seoul, Korea.
Transplant Proc. 2005 Mar;37(2):1235-7. doi: 10.1016/j.transproceed.2004.11.037.
Renal recipients with hepatitis B virus (HBV) should be treated with prolonged lamivudine. However, lamivudine resistance usually results after YMDD mutation within the HBV polymerase gene. Thereupon, the aim of this study was to investigate the genotypic resistance to lamivudine among renal transplant recipients to identify its effect on the clinical course of HBV in these patients. Between March 1997 and September 2003, eight of 17 renal transplant patients with hepatitis B virus were enrolled into this study and treated with 100 mg of lamivudine once each day. We amplified a selected region of the polymerase gene of HBV in order to confirm mutations in the YMDD motif. Mutations of YMDD region were observed in five of eight patients (62.5%). Out of five patients positive for HBV DNA, three (60%) showed genotypic resistance (YMDD mutation) with a normal ALT level. Two patients converted to HBV DNA negative. But, they were not associated with HBeAg seroconversion. Out of three patients who were pretransplant HBV DNA negative, genotypic resistance was observed in two patients (67%) revealing both positivity of HBe antibody and negativity of HBV DNA. In conclusion, although a normal ALT level and HBV DNA negative are maintained, the mutation of the YMDD locus may develop. Accordingly, we suggest that if the YMDD mutation is not involved in the progression of hepatitis B, lamivudine therapy should be continued despite genotypic resistance.
乙型肝炎病毒（HBV）感染的肾移植受者应接受长期拉米夫定治疗。然而，拉米夫定耐药通常是由HBV聚合酶基因中的YMDD突变导致的。因此，本研究的目的是调查肾移植受者对拉米夫定的基因型耐药情况，以确定其对这些患者HBV临床病程的影响。1997年3月至2003年9月期间，17例乙型肝炎病毒感染的肾移植患者中有8例纳入本研究，接受每日100毫克拉米夫定治疗。我们扩增了HBV聚合酶基因的一个选定区域，以确认YMDD基序中的突变。8例患者中有5例（62.5%）观察到YMDD区域突变。在5例HBV DNA阳性患者中，3例（60%）表现出基因型耐药（YMDD突变），谷丙转氨酶（ALT）水平正常。2例患者转为HBV DNA阴性。但它们与HBeAg血清学转换无关。在3例移植前HBV DNA阴性的患者中，2例（67%）观察到基因型耐药，显示HBe抗体阳性和HBV DNA阴性。总之，尽管维持了正常的ALT水平和HBV DNA阴性，但YMDD位点可能会发生突变。因此，我们建议，如果YMDD突变与乙型肝炎的进展无关，尽管存在基因型耐药，拉米夫定治疗仍应继续。
