Histological findings in protocol biopsies following pediatric liver transplant: Low incidence of abnormalities at 5years
Histological findings in protocol biopsies following pediatric liver transplant: Low incidence of abnormalities at 5years
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DOI：
10.1111/petr.13212
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发表时间：
2018-08-01
影响因子：
1.3
通讯作者：
Evans, Helen M.
中科院分区：
文献类型：
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作者：
Sheikh, Amin;Chau, Kai Y.;Evans, Helen M.
组织学异常，包括慢性肝炎，纤维化和脂肪变性，越来越多地报告在肝活检的儿童LT后，这些变化可能是渐进的，并代表一种形式的排斥反应。肝脏生化通常最初是正常的。我们的肝移植计划开始于2002年，在肝移植后的第一年使用他克莫司和低剂量的类固醇。患者在肝移植后1年停止类固醇之前进行了一次活检，然后在50年和此后每50年进行一次活检。3个月和12个月后他克莫司的目标水平分别为5- 8 g/L和3-5g/L。2002年至2009年，共进行了51例LT;分别有50例（98%）和49例（96%）患者存活1年和5年。共有43名患者（中位年龄为LT 2.3岁）在1年时（16名男性; LT后中位时间为12.5个月）和44名患者（20名男性; LT后中位时间为5.1年）接受了方案活检。5年后，3例转入成人服务，1例因移植失败再次移植，1例移居海外。由2名病理学家审查活检。大多数患者（31/44）在5年时接受他克莫司单药治疗。在1年和5年时，43例活检中分别有29例（67.5%）和44例活检中有31例（71%）正常。44例中有2例在5年时发生慢性移植物肝炎。在1年和5年时，43例中有2例和44例中有1例出现孤立性纤维化，43例中有3例和44例中有3例出现脂肪变性，43例中有3例和44例中有4例出现急性排斥反应。其他发现主要包括胆道改变（1年和5年时分别为6/43和3/44）。5年时他克莫司水平略高于预期（中位谷水平5.8 g/L）。他克莫司和低剂量类固醇免疫抑制方案治疗1年，随后进行他克莫司单药治疗，大多数PLB正常，5年时未观察到进行性变化。与其他LT项目相比，我们在5年内慢性移植物肝炎、脂肪变性和纤维化的发生率较低。然而，5年时他克莫司水平高于计划水平，这可能起了一定作用。还需要进一步评估以确定皮质类固醇使用对线性生长和骨矿物质密度的潜在长期不良影响。
Histological abnormalities, including chronic hepatitis, fibrosis, and steatosis, are increasingly reported in liver biopsies of children after LT. These changes may be progressive and represent a form of rejection. Liver biochemistry is often initially normal. Our LT program began in 2002, utilizing tacrolimus and low-dose steroids for the first year post-LT. Patients undergo a protocol biopsy at 1year post-LT prior to stopping steroids, then at 5years and every 5years thereafter. Target tacrolimus levels are 5-8g/L and 3-5g/L after 3 and 12months, respectively. Between 2002 and 2009, 51 LT were performed; 50 (98%) and 49 (96%) patients survived for 1 and 5years, respectively. A total of 43 patients (median age at LT 2.3years) underwent a protocol biopsy at 1year (16 male; median time post-LT 12.5months), and 44 (20 male; median time post-LT 5.1years) at 5years. By 5years, 3 had transferred to adult services; 1 was re-transplanted for graft failure and 1 moved overseas. Biopsies were reviewed by 2 pathologists. Most patients (31/44) were on tacrolimus monotherapy at 5years. At 1 and 5years, 29 of 43 (67.5%) and 31 of 44 (71%) biopsies were normal, respectively. Two of 44 had chronic allograft hepatitis at 5years. Two of 43 and 1 of 44 had isolated fibrosis, 3 of 43 and 3 of 44 steatosis, and 3 of 43 and 4 of 44 acute rejection at 1 and 5years, respectively. Other findings included predominantly biliary changes (6/43 & 3/44 at 1 and 5years, respectively). Tacrolimus levels at 5years were slightly higher than anticipated (median trough level 5.8g/L). With an immunosuppressive regimen of tacrolimus and low-dose steroids for 1year followed by tacrolimus monotherapy thereafter, the majority of PLB were normal and no progressive changes were observed at 5years. Compared to other LT programs, we have lower rates of chronic allograft hepatitis, steatosis, and fibrosis at 5years. However, the tacrolimus levels at 5years were higher than planned and this may have played a role. Further evaluation is also required to determine the potential long-term adverse effects of corticosteroid use on linear growth and bone mineral density.