背景:肝移植(LT)使糖原贮积型(GSD)1b的空腹耐受性正常化。然而,关于纠正中性粒细胞减少症的LT后报告结果,感染风险和生长是多种多样的。钠-葡萄糖协同转运蛋白-2(SGLT2)抑制剂最近已被证明可以改善GSD1b患者的中性粒细胞减少症。
方法:在这项单中心回顾性研究中,我们回顾了所有接受GSD1bLT的儿童.中性粒细胞减少症,粒细胞集落刺激因子(G-CSF)的剂量,计划外的医院就诊,人体测量学,移植排斥,生存,并对达格列净的效果进行了分析。收集来自在LT和免疫抑制水平后1年、5年和10年获得的协议活检的数据。
结果:八个孩子(6名女性),都是移植前的G-CSF,在中位年龄3.6岁(IQR3.3-5.1)时接受GSD1b尸体LT,平均随访时间10.3年(95%CI7.5-13.1).中性粒细胞计数和G-CSF需求在LT后没有改善。尽管感染导致计划外住院人数减少(0.98[95%CI0.76-1.26]vs.每人每年0.49[95%CI0.41至0.57],p<0.01)观察到,胃肠道不适和移植物功能障碍是LT前后住院负担相似的原因。LT术后体重指数(BMI)降低(Z评分1.47[95CI0.39-2.23]vs.0.56[95%CI-0.74至1.45],p=0.02),身高没有明显变化。尽管所有儿童和移植物都幸存下来,75%的接受者出现了拒绝,尽管有足够的免疫抑制水平,有两个孩子在他们的5年协议活检中被发现发展了显著的纤维化。尽管达格列净允许停止G-CSF,未观察到中性粒细胞计数改善.尽管如此,观察到达格列净治疗后胃肠道和感染相关发病率降低.
结论:尽管LT使GSD1b的空腹耐受性正常化,并减少因感染引起的住院率,感染和胃肠道表现的发病率持续存在。我们队列中的儿童经历了高排斥率,需要滴定免疫抑制以平衡感染风险与器官排斥反应。未来的研究应该调查早期引入SGLT2抑制剂后LT是否会影响该组的发病率。
BACKGROUND: Liver transplantation (LT) normalizes fasting tolerance in glycogen storage disease type (GSD) 1b. However, reported outcomes post-LT with respect to correction of neutropenia, infection risk and growth are varied. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been recently shown to improve neutropenia in GSD1b patients.
METHODS: In this single-center retrospective study, we reviewed all children who underwent LT for GSD1b. Neutropenia, dose of granulocyte colony-stimulating factor (G-CSF), unplanned hospital attendance, anthropometrics, graft rejection, survival, and the effects of dapagliflozin were analyzed. Data from protocol biopsies obtained at 1, 5, and 10 years post-LT and immunosuppression levels were collected.
RESULTS: Eight children (6 female), all on G-CSF pre-transplant, underwent cadaveric LT for GSD1b at median age 3.6 years (IQR 3.3-5.1) with mean follow-up time of 10.3 years (95% CI 7.5-13.1). Neutrophil count and G-CSF requirement did not improve post-LT. Although a reduction in unplanned hospital attendance due to infection (0.98 [95% CI 0.76-1.26] vs. 0.49 [95% CI 0.41 to 0.57] per person-year, p < 0.01) was observed, gastrointestinal complaints and graft dysfunction accounted for a similar hospitalization burden pre- versus post-LT. Body mass index (BMI) reduced post-LT (Z-score 1.47 [95%CI 0.39-2.23] vs. 0.56 [95% CI -0.74 to 1.45], p = 0.02), with no significant change in height. Although all children and grafts have survived, 75% of recipients developed rejection, despite adequate immunosuppression levels, with two children having been found to have developed significant fibrosis on their 5-year protocol biopsy. Although dapagliflozin allowed cessation of G-CSF, no improvement in neutrophil count was observed. Despite this, a reduction in gastrointestinal and infection-related morbidity was noted following dapagliflozin.
CONCLUSIONS: Although LT normalizes fasting tolerance in GSD1b and reduces hospital attendance due to infection, morbidity from infection and gastrointestinal manifestations persist. Children in our cohort experienced high rates of rejection necessitating titration of immunosuppression to balance risk of infection against organ rejection. Future studies should investigate whether early introduction of SGLT2 inhibitors post-LT impact morbidity in this group.