Is severe progressive liver disease caused by alpha-1-antitrypsin deficiency more common in children or adults?
Is severe progressive liver disease caused by alpha-1-antitrypsin deficiency more common in children or adults?
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DOI：
10.1002/lt.24434
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发表时间：
2016-07-01
影响因子：
4.6
通讯作者：
Perlmutter, David H.
中科院分区：
文献类型：
--
作者：
Chu, Andrew S.;Chopra, Kapil B.;Perlmutter, David H.
已知经典形式的α -1抗胰蛋白酶缺乏症（A1ATD）可导致儿童和成人肝脏疾病，但关于严重进展性肝脏疾病的风险和需要肝移植的信息相对较少。为了更好地了解新发展的药理学、遗传学和细胞疗法如何根据进展性肝病的风险进行靶向治疗，我们试图确定A1ATD作为严重肝病病因的年龄分布，因为需要肝移植。使用1991-2012年3个美国肝移植数据库，我们发现1677例诊断为A1ATD的肝移植中77.2%为成人。高峰年龄范围为50-64岁。使用包含特定A1ATD表型的2个数据库，我们发现许多诊断为A1ATD的接受肝移植的成年人是杂合子，并且有其他潜在的肝脏疾病原因，最明显的是肥胖和酒精滥用。然而，即使排除这些病例，只考虑ZZ和SZ表型，成人中需要移植的严重肝脏疾病的可能性也超过2.5倍。分析还显示，男性患乳腺癌的风险明显增加。在儿科组，几乎所有的移植手术都是在5岁以下的儿童中进行的。总之，A1ATD导致进行性肝病最常见于成人，男性处于最高风险类别。在儿科组中，5岁以下儿童的风险最高。这些结果表明，A1ATD最常通过类似于年龄依赖性退行性疾病的机制引起肝脏疾病，而在儿童中较少通过强大的调节剂引起肝脏疾病。肝移植22 886-894 2016 AASLD
The classical form of alpha-1-antitrypsin deficiency (A1ATD) is known to cause liver disease in children and adults, but there is relatively little information about the risk of severe, progressive liver disease and the need for liver transplantation. To better understand how newly evolving pharmacological, genetic, and cellular therapies may be targeted according to risk for progressive liver disease, we sought to determine the age distribution of A1ATD as a cause of severe liver disease, as defined by the need for liver transplantation. Using 3 US liver transplantation databases for the period 1991-2012, we found 77.2% of 1677 liver transplants with a reported diagnosis of A1ATD were adults. The peak age range was 50-64 years. Using 2 of the databases which included specific A1AT phenotypes, we found that many of these adults who undergo liver transplantation with A1ATD as the diagnosis are heterozygotes and have other potential causes of liver disease, most notably obesity and ethanol abuse. However, even when these cases are excluded and only ZZ and SZ phenotypes are considered, severe liver disease requiring transplantation is more than 2.5 times as likely in adults. The analysis also showed a markedly increased risk for males. In the pediatric group, almost all of the transplants are done in children less than 5 years of age. In conclusion, A1ATD causes progressive liver disease most commonly in adults with males in the highest risk category. In the pediatric group, children less than 5 years of age are highest in risk. These results suggest that A1ATD most commonly causes liver disease by mechanisms similar to age-dependent degenerative diseases and more rarely in children by powerful modifiers. Liver Transplantation 22 886-894 2016 AASLD