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目的加强对造血干细胞移植中HBV感染的重视,注重早期干预,提高移植成功率。方法回顾性分析97例异基因造血干细胞移植患儿的临床资料,通过对2例HBV感染的诊治体会结合文献复习。结果2001年5月至2008年5月在上海交通大学附属上海儿童医学中心接受异基因造血干细胞移植的97例患儿中,2例分别在移植后41d(病例1)、15个月(病例2)发生HBV感染。病例1移植前肝功能正常,乙肝二对半检查阴性,回顾性分析发现该患儿移植时HBV正处于潜伏状态(HBV-DNA 1.17×106copies·mL-1)。该患儿乙肝来势凶猛,移植后41～43d出现巩膜明显黄染并伴大量腹水,移植后46d迅速发展至肝、肾功能衰竭,出现少尿,凝血酶原时间38.4s,部分凝血酶原时间>120s,凝血酶时间>100s,Cr 251μmol·L-1,ALT 3195U·L-1,血清总胆红素7mg.L-1,直接胆红素2.8mg·L-1,HBV-DNA 1.08×108copies·mL-1,经拉米夫定等积极治疗2周后好转。移植后130d随着移植物抗宿主病(GVHD)的复燃和免疫抑制药物的加强应用,HBV再度活跃,HBV-DNA从原已控制的3.50×104copies·mL-1逐升至2.05×106copies·mL-1,移植后315d出现HBVYMDD(+)变异株,遂予阿德福韦酯联合治疗至今(移植后3.5年),目前肝、肾功能正常。病例2白血病起病初及干细胞移植前均示HBs-Ab(+)、HBc-Ab(+)、HBe-Ab(+),ALT和HBV-DNA正常,移植后12个月发生慢性广泛性GVHD,加强抗排异治疗后于移植后15个月复查发现:ALT 168U·L-1,HBV-DNA升至5×108copies·mL-1,出现HBs-Ag(+)和HBe-Ag(+)。予拉米夫定治疗至移植后4.5年,目前ALT40～80U·L-1,HBV-DNA 1×103～1×104copies·mL-1。结论乙肝在移植患儿中并不少见,长期的免疫抑制治疗常使病情反复,加强病毒监测、重视早期干预至关重要;移植前HBV-DNA检测有助于发现潜伏期患儿;HBs-Ab(+)、HBe-Ab(+)和HBc-Ab(+)患儿在强烈免疫抑制下仍有HBV复燃的风险。
Objective To strengthen the emphasis on HBV infection in hematopoietic stem cell transplantation, pay attention to early intervention and improve the success rate of transplantation. Methods A retrospective analysis of 97 cases of allogeneic hematopoietic stem cell transplantation in children with clinical data, through the diagnosis and treatment of 2 cases of HBV infection combined with the literature review. Results Of the 97 children who received allogeneic hematopoietic stem cell transplantation at the Shanghai Children’s Medical Center affiliated to Shanghai Jiao Tong University from May 2001 to May 2008, two of them were treated at 41 days (case 1) and 15 months (case 2) ) HBV infection occurs. Case 1 liver function before transplantation, hepatitis B two-and-a-half negative, retrospective analysis found that children with HBV transplantation is in a latent state (HBV-DNA 1.17 × 106copies · mL-1). The children with ferocious Hepatitis B, 41 ~ 43d after transplantation appeared scleral significant yellow dye and a large number of ascites, 46d after transplantation to rapid development of liver and kidney failure, oliguria, prothrombin time 38.4s, partial prothrombin time Thrombin time> 100s, Cr 251μmol·L-1, ALT 3195U · L-1, serum total bilirubin 7mg.L-1, direct bilirubin 2.8mg · L-1 and HBV-DNA 1.08 × 108copies · mL-1, after lamivudine and other active treatment improved after 2 weeks. At 130 days after transplantation, with the relapse of graft-versus-host disease (GVHD) and the enhanced use of immunosuppressive drugs, HBV became active again and HBV-DNA rose from 3.50 × 104 copies · mL-1 to 2.05 × 106 copies mL-1, HBVYMDD (+) mutants appeared 315 days after transplantation, then to adefovir dipivoxil combined treatment (3.5 years after transplantation), the current liver and kidney function is normal. Case 2 Leukemia at the beginning of onset and before stem cell transplantation showed HBs-Ab (+), HBc-Ab (+), HBe-Ab (+), ALT and HBV-DNA were normal, 12 months after transplantation, chronic extensive GVHD , HBs-Ag (+) and HBe-Ag (+) were increased after HBV DNA was raised to 5 × 108 copies · mL-1 at ALU 168U · L-1 after 15 months of transplantation. . To lamivudine treatment to 4.5 years after transplantation, the current ALT 40 ~ 80U · L-1, HBV-DNA 1 × 103 ~ 1 × 104copies · mL-1. Conclusion Hepatitis B is not uncommon in children with transplantation. Long-term immunosuppressive therapy often makes the disease repeated. It is very important to strengthen virus surveillance and pay attention to early intervention. Pre-transplant HBV-DNA test can help to find children with latent period. HBs-Ab +), HBe-Ab (+) and HBc-Ab (+) patients still have the risk of HBV rekindling under strong immunosuppression.