Santantonio T, Gunther S, Sterneck M, Rendina M, Messner M, Launois B, Francavilla A, Pastore G, Will H
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Germany.
Hepatogastroenterology. 1999 May-Jun;46(27):1848-54.
BACKGROUND/AIMS: HBV reinfection of transplant livers occurs frequently even in the presence of high doses of anti-HBs immunoglobulins. We analyzed, retrospectively, whether and which type of S-gene variants were selected by long-term polyclonal anti-HBs (HBIg) treatment leading to reinfection of patients transplanted because of chronic HBs-positive end-stage liver disease.
The preS2/S gene of the viral genomes obtained from sera before transplantation and during HBV reinfection was amplified by PCR and directly sequenced.
According to transaminase and HBV DNA hybridization analysis, 3/18 (17%) liver transplant patients had HBV and hepatitis recurrence during anti-HBs therapy. A HBV S-gene mutant containing a G to A nucleotide mutation at position 587, converting Glycine to Arginine (G145A), was identified in all three patients as the dominant population at reinfection but not pre-transplantation. Contrary to the S-gene, no consistent nucleotide changes were found in the pre-S2 region of HBV genomes when comparing the reinfection and pre-transplantation samples.
These data demonstrate that long-term polyclonal anti-HBs immunoprophylaxis selected the most commonly described G145R S-gene escape HBV variant which became the dominant virus population and was responsible for graft infection. Therefore, immunoglobulins with high affinity for the G145R HBs variant should be included in HBIg to prevent recurrent HBV infection in transplant patients.
背景/目的：即使使用高剂量的抗-HBs免疫球蛋白，移植肝的HBV再感染仍频繁发生。我们回顾性分析了长期多克隆抗-HBs（HBIg）治疗是否以及选择了哪种类型的S基因变异体，导致因慢性HBs阳性终末期肝病而接受移植的患者发生再感染。
通过PCR扩增移植前和HBV再感染期间血清中获得的病毒基因组的preS2/S基因，并直接测序。
根据转氨酶和HBV DNA杂交分析，18例肝移植患者中有3例（17%）在抗-HBs治疗期间出现HBV和肝炎复发。在所有3例患者中均鉴定出一种HBV S基因突变体，其在587位核苷酸处发生G到A的突变，导致甘氨酸转变为精氨酸（G145A），该突变体在再感染时而非移植前成为优势种群。与S基因相反，比较再感染和移植前样本时，在HBV基因组的pre-S2区域未发现一致的核苷酸变化。
这些数据表明，长期多克隆抗-HBs免疫预防选择了最常见的G145R S基因逃逸HBV变异体，该变异体成为优势病毒种群并导致移植物感染。因此，HBIg中应包含对G145R HBs变异体具有高亲和力的免疫球蛋白，以预防移植患者的HBV再感染。
