Systematic review: the natural history of alpha‐1 antitrypsin deficiency, and associated liver disease

Abstract

Summary Background Alpha‐1 antitrypsin deficiency (AATD) is estimated to affect three million people worldwide. It causes liver disease in a proportion of carriers of the PiS and PiZ allele due to the formation and retention of polymers within the endoplasmic reticulum of hepatocytes. The reason for this selective penetrance is not known. Although clinical trials are underway, liver transplantation is the only effective treatment for liver disease due to AATD. Aims To report the prevalence and natural history of liver disease among individuals with AATD, and assess the outcomes of liver transplantation through systematic review. Methods A comprehensive search was conducted across multiple databases. Two independent authors selected the articles and assessed bias using the Newcastle‐Ottawa Scale. Data were pooled for analysis, where comparable outcomes were reported. Results Thirty‐five studies were identified related to disease progression and 12 for the treatment of AATD. Seven per cent of children were reported to develop liver cirrhosis, with 16.5% of individuals presenting in childhood requiring liver transplantation. Of those surviving to adulthood, 10.5% had liver cirrhosis and 14.7% required transplantation. Liver transplantation was the only effective treatment reported and outcomes compare favourably to other indications, with 5‐year survival reported as over 90% in children and over 80% in adults. Discussion The clinical course of liver disease in individuals with AATD remains poorly understood, but affects about 10% of those with AATD. More research is required to identify those patients at risk of developing liver disease at an early stage, and to provide alternative treatments to liver transplantation.

Heterozygosity for the Alpha‐1‐Antitrypsin Z Allele in Cirrhosis Is Associated With More Advanced Disease

“…(1) Although the heterozygous Pi*Z carriage is fairly common, the homozygous genotype (Pi*ZZ) is comparably rare (1:2000 to 1:4000). (2) Because the course of Pi*ZZ-related liver disease remains greatly understudied, we report a case of a Pi*ZZ patient with a rapid decompensation of liver disease.…”

Advances in managing COPD related to α1‐antitrypsin deficiency: An under‐recognized genetic disorder

“…With regard to liver transplantation, there are few reports of outcomes in patients with AATD . Reviews of patient databases and case series suggest that AAT levels may normalize following liver transplantation in adults and children, although it is unclear whether this procedure has an impact on pulmonary outcomes .…”

Presentation and prognosis of liver disease in alpha-1 antitrypsin deficiency

“…A proportion (approximately 1%) of those children presenting in infancy recover to enjoy years of good health whilst later on developing severe disease [7] and require liver transplantation. This commonly occurs between the ages of 4 and 8 [8], but sometimes later on in the second decade of life [9,10]. Other children have no signs of disease during infancy but are diagnosed incidentally later in childhood following abnormal liver biochemistry tests [10,11] in response to screening of family members of an affected individual [12].…”

“…AATD more commonly affects the Caucasian population, and in a recent systematic review, 97% of children diagnosed with the condition were of Caucasian origin [9]. Interestingly, although males comprise only 35% of children diagnosed with AATD, boys accounted for over 60% of children undergoing liver transplantation for AATD, suggesting that disease progression is more likely in males [9].…”