Long-term Outcomes of Living-donor Liver Transplantation for Progressive Familial Intrahepatic Cholestasis Type 1
Long-term Outcomes of Living-donor Liver Transplantation for Progressive Familial Intrahepatic Cholestasis Type 1
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DOI：
10.1097/mpg.0000000000002983
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发表时间：
2021-03-01
影响因子：
2.9
通讯作者：
Uemoto, Shiji
中科院分区：
文献类型：
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作者：
Okamoto, Tatsuya;Sonoda, Mari;Uemoto, Shiji
目的：进行性家族性肝内胆汁淤积1型（PFIC-1）是一种常染色体隐性遗传疾病，以胆汁淤积、黄疸和顽固性瘙痒为特征。在一些PFIC-1患者中，肝硬化和终末期肝病发展并导致肝移植（LT）。在这项观察性研究中，我们试图阐明PFIC-1 LT的长期结局和有利结局的预测因素。研究方法：该研究队列由12名PFIC-1患者组成，他们在过去30年（1990-2019）中接受了活体肝移植（LDLT）。我们比较了LDLT成功和不成功患者的临床表现和ATP 8B 1突变类型。结果：12例患者中5例LDLT失败，25年生存率为58%。LDLT后的身体生长比较显示，LDLT不成功的患者的身高明显迟缓，这些患者出现严重和持续性腹泻。ATP 8B 1基因型分析显示，移码，剪接，和大的缺失突变发生在成功的情况下更常见，而错义突变发生在不成功的情况下更频繁。两组中没有相同的突变。结论：这些结果提示肝移植后的预后与肝外表现，尤其是肠功能有关。进一步研究ATP 8B 1基因型与肠功能之间的相关性可能有助于识别PFIC-1患者，这些患者将获得良好的LT后结局。
Objectives: Progressive familial intrahepatic cholestasis type 1 (PFIC-1), an autosomal recessive disorder, is characterized by cholestasis, jaundice, and refractory pruritus. In some patients with PFIC-1, liver cirrhosis and end-stage liver disease develop and lead to liver transplantation (LT). In this observational study, we sought to clarify the long-term outcomes of LT for PFIC-1 and predictors of favorable outcomes. Methods: The study cohort constituted 12 patients with PFIC-1 who had undergone living donor liver transplantation (LDLT) during the previous 3 decades (1990-2019). We compared the clinical manifestations and type of ATP8B1 mutations between patients in whom LDLT had been successful and those in whom it had been unsuccessful. Results: LDLT failed in 5 of the 12 patients and the 25-year survival rate was 58%. Comparison of physical growth after LDLT revealed significant retardation of stature in patients in whom LDLT had been unsuccessful; these patients developed severe and persistent diarrhea. ATP8B1 genotypic analysis revealed that frameshifting, splicing, and large deletion mutations occurred more commonly in successful cases, whereas missense mutations occurred more frequently in unsuccessful cases. No mutations were identical in the 2 groups. Conclusions: These results suggest an association between post-LT outcomes and extrahepatic manifestations, especially intestinal function. Further investigation of correlations between ATP8B1 genotypes and intestinal function could help to identify patients with PFIC-1 who will achieve favorable post-LT outcomes.