Original articles
Factors associated with advanced liver disease in adults with alpha1-antitrypsin deficiency

https://doi.org/10.1016/S1542-3565(05)00082-0Get rights and content

Background & Aims: Alpha1-antitrypsin deficiency (AAT) is an autosomal recessive disease that affects 1 in 2500 persons and might lead to cirrhosis. Our study aim was to characterize the liver disease in AAT and identify factors associated with advanced liver disease. Methods: A cohort of the Alpha-1 Foundation Registry who reported liver disease was surveyed with a liver disease questionnaire to obtain information related to liver disease, liver transplantation, and AAT phenotype. Results: One hundred sixty-five of the 2175 participants in the registry reported a history of jaundice or liver disease, and 139 (84.2%) completed the questionnaire. Of these, 71.3% were PiZZ, 18.0% were PiMZ, and 5.7% did not know their phenotype. Analysis of 104 participants with a known age of diagnosis included 30 participants diagnosed with liver disease before 18 years, of whom 15 had advanced liver disease defined as liver transplantation or listed for liver transplantation. No differences in age, age at diagnosis, gender, race, phenotype, or infant jaundice were identified. Seventy-four participants were diagnosed after age 18 years, of whom 25 had advanced liver disease. In this group, advanced liver disease was associated with male gender (P = .006) and a greater mean body mass index (P = .01), but not with race, Pi phenotype, infant jaundice, diabetes, or hypercholesterolemia. Viral hepatitis was more frequently reported in the nontransplant group (34.7% vs 8.0%, P = .01), and the mean daily alcohol use was significantly greater in this group (P = .04). Conclusions: Our results suggest that male gender and obesity but not alcohol or viral hepatitis predispose to advanced liver disease in adults with AAT.

Section snippets

Study design

One hundred sixty-five participants in the Alpha-1 Foundation Registry who reported jaundice or liver disease were mailed questionnaires that queried for demographic data, history of jaundice, hepatitis virus exposure, alcohol use, diabetes, high cholesterol, liver biopsy, and final diagnosis. Parents completed questionnaires for minor children. Telephone interviews were performed to clarify responses and capture data from some of the questionnaire nonresponders. The Registry requires signed

Study population

At the time of study initiation, the Alpha-1 Foundation Registry was composed of 2175 participants, of whom 165 (7.6%) had reported symptoms of jaundice or liver disease. One hundred thirty-nine (84.2%) of the 165 registrants reporting a history of liver disease or jaundice in the Alpha-1 Foundation Registry agreed to participate in the study (Table 1). The mean age was 43.5 ± 20.9 years with a range from 1–75 years. The mean age at diagnosis of liver disease was 31 ± 21 years (range, 0–68

Discussion

AAT deficiency is a relatively rare cause of advanced liver disease in children and adults. Thus, the prevalence of liver disease and its natural history in AAT-deficient individuals have been difficult to assess. In addition, factors potentially contributing to the progression of liver disease in AAT deficiency have not been well studied. This report is the largest series of patients with liver disease associated with AAT deficiency and has identified obesity as a potential risk factor in

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    Copyright © 2005 American Gastroenterological Association. Published by Elsevier Ltd. All rights reserved.