CLINICAL IMPROVEMENT AND AMYLOID REGRESSION AFTER LIVER-TRANSPLANTATION IN HEREDITARY TRANSTHYRETIN AMYLOIDOSIS
CLINICAL IMPROVEMENT AND AMYLOID REGRESSION AFTER LIVER-TRANSPLANTATION IN HEREDITARY TRANSTHYRETIN AMYLOIDOSIS
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DOI：
10.1016/0140-6736(93)93127-m
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发表时间：
1993-05-01
期刊：
影响因子：
168.9
通讯作者：
PEPYS, MB
中科院分区：
文献类型：
--
作者：
HOLMGREN, G;ERICZON, BG;PEPYS, MB
家族性淀粉样多发性神经病是一种致死性常染色体显性遗传病。进行性外周和自主神经病变与淀粉样蛋白的神经和内脏沉积相关，最常见的来源于血浆蛋白甲状腺素运载蛋白的Met-30变体。我们以前曾报道过原位肝移植会导致血浆中的野生型甲状腺素运载蛋白被供体迅速替代。我们现在报告移植后1-2年的临床结果，前4名患者中有3名患者的总体健康状况、行走能力和肠功能得到改善，其中1名患者恢复了正常的膀胱和肠功能。周围神经病变几乎没有客观改善。第四例患者，神经功能缺损最严重，术后病程复杂，没有改善，但与移植前的无情进展相比，没有进一步恶化。放射性标记的血清淀粉样蛋白P成分的定量放射性造影显示内脏淀粉样蛋白沉积在所有三个研究的患者，在两个谁是连续的存款回归移植后与临床改善。另一名FAP患者也进行了2年的前瞻性监测，但没有接受移植，正如预期的那样，表现出神经病变的进展和内脏淀粉样蛋白沉积增加。神经功能衰退停止，淀粉样蛋白沉积可以动员。现在必须确定这一程序的最佳时机和长期结果。
Familial amyloid polyneuropathy (FAP) is a fatal autosomal dominant disorder. Progressive peripheral and autonomic neuropathy are associated with neural and visceral deposition of amyloid, derived most commonly from the Met-30 variant of the plasma protein transthyretin. We have reported previously that orthotopic liver transplantation causes prompt replacement of variant transthyretin by the donor wild-type in the plasma. We now report clinical outcome 1-2 years after transplantation.Three of the first four patients have improved general wellbeing, walking ability, and bowel function, and one of them has regained normal bladder and bowel function. There has been little objective improvement in peripheral neuropathy. The fourth patient, who had the most severe neurological deficits and a complicated postoperative course, has not improved but there has been no further deterioration in contrast to the inexorable progression before transplantation. Quantitative scintigraphy with radiolabelled serum amyloid P component showed visceral amyloid deposits in all three patients studied; in two who were followed serially the deposits regressed after transplantation in association with the clinical improvement. Another FAP patient who was also monitored prospectively for 2 years but who did not undergo transplantation, showed, as expected, progression of neuropathy and increased visceral amyloid deposition.Liver transplantation does therefore have important benefits in FAP during the first 2 years after surgery. Neurological decline is halted and amyloid deposits can be mobilised. The best timing and long-term results of the procedure must now be established.