INCREASED RISK OF CHRONIC LIVER-FAILURE IN ADULTS WITH HETEROZYGOUS ALPHA(1)-ANTITRYPSIN DEFICIENCY

Controversy exists whether patients who are genetically heterozygous f or al-antitrypsin deficiency (alpha(1)ATD), carrying a single PIZ all ele, are at increased risk of developing chronic liver disease. In the se investigations, we determined the prevalence of heterozygous alpha( 1)AT phenotypes (PI MZ, PI SZ) in a well-characterized cohort of patie nts presenting with chronic liver failure before orthotopic liver tran splantation (OLT). We analyzed data collected from all adult patients (n = 641) who underwent OLT at our tertiary referral center between Ma rch 1984 and December 1996, Study patients entered a prospective proto col designed to test for all known etiologies of liver disease. Comple te testing including a,AT phenotyping was successfully performed in 59 9 adults. We compared the overall number of heterozygous PIZ carriers in our OLT cohort with established prevalence figures for general and regional American populations, and examined their distribution among various liver disease subgroups. Fifty-one patients were found to be h eterozygous carriers of a single PIZ allele for alpha(1)AT. The predo minant phenotype in our transplantation cohort was PI MZ, identified i n 49 patients (8.2%), which is a significantly higher prevalence than that reported from previous American population studies (2%-4%), Addit ionally, a significantly greater number of PI MZ carriers existed in p atients with cryptogenic cirrhosis compared with other liver disease c ategories (26.9%; P < .001). These data suggest that individuals carry ing a single PIZ allele for alpha(1)AT may be at increased risk of de veloping cirrhosis and liver failure, even in the absence of an identi fiable coexisting liver disease.