Ghany M G, Ayola B, Villamil F G, Gish R G, Rojter S, Vierling J M, Lok A S
University of Michigan and VA Medical Center, Ann Arbor 48109, USA.
Hepatology. 1998 Jan;27(1):213-22. doi: 10.1002/hep.510270133.
Long-term hepatitis B immune globulin (HBIG) has been shown to reduce hepatitis B virus (HBV) reinfection in patients transplanted for hepatitis B. The aim of this study was to determine the prevalence of HBV S gene mutations in liver transplant recipients who developed recurrent hepatitis B despite HBIG prophylaxis, and to determine if these mutations can revert after withdrawal of HBIG. The entire S gene sequences in pre- and posttransplant sera from 20 patients who developed recurrent hepatitis B despite HBIG prophylaxis were compared. Ten (50%) patients had 18 amino acid substitutions involving the 'a' determinant in the posttransplant samples. These mutations were absent in 93% of the pretransplantation clones analyzed. There was a significant correlation between the development of mutations in the 'a' determinant region and the duration of HBIG therapy. Most of the mutations result in changes in predicted antigenicity of the S protein. During follow-up, mutations in 14 (78%) of 18 affected codons in the 'a' determinant region reverted back to the pretransplantation sequences; only 1 codon had a de novo change after the withdrawal of HBIG. Two control patients who did not receive HBIG had no change in the 'a' determinant in their posttransplantation samples. These data support the hypothesis that mutations in the S gene were induced or selected by immune pressure exerted by HBIG. HBV S mutants may play a role in HBV reinfection in liver transplant recipients who received HBIG prophylaxis.
长期使用乙肝免疫球蛋白（HBIG）已被证明可降低乙肝患者肝移植后的乙肝病毒（HBV）再感染率。本研究的目的是确定在接受HBIG预防治疗后仍发生乙肝复发的肝移植受者中HBV S基因突变的发生率，并确定这些突变在停用HBIG后是否会逆转。比较了20例尽管接受HBIG预防治疗仍发生乙肝复发的患者移植前和移植后血清中的整个S基因序列。10例（50%）患者在移植后样本中有18个氨基酸替代，涉及“a”决定簇。在分析的93%的移植前克隆中未发现这些突变。“a”决定簇区域突变的发生与HBIG治疗持续时间之间存在显著相关性。大多数突变导致S蛋白预测抗原性的改变。在随访期间，“a”决定簇区域18个受影响密码子中的14个（78%）突变恢复到移植前序列；停用HBIG后只有1个密码子出现新生变化。2例未接受HBIG的对照患者移植后样本中的“a”决定簇无变化。这些数据支持以下假设：S基因中的突变是由HBIG施加的免疫压力诱导或选择的。HBV S突变体可能在接受HBIG预防治疗的肝移植受者的HBV再感染中起作用。
