Liver disease in adults with severe alpha-1-antitrypsin deficiency

BACKGROUND: The proportion of adults with liver disease due to severe alpha-1-antitrypsin deficiency (AATD), with PiZZ phenotype, is not clear. The markers of the AATD liver disease, how it progresses, and measures for its prevention have not been established. The aim of this study was to analyze the risk of liver disease in individuals with severe AAT deficiency (PiZZ). METHODS: Longitudinal clinical and laboratory data were obtained from the Swedish National registers, by cross-linkage between the Swedish national AATD register, the Swedish National Patient Register, the National Cancer Register and the National Causes of Death Register. RESULTS: A total of 1595 PiZZ individuals were included in the analyses. The mean follow-up time was 12 years (range 0.3–24). The mean number of follow-ups was 5 (range 2–15). Two or more liver function tests (LFTs) were available in 1123 individuals, and 26% of them (n = 290) had repeated elevated LFTs during the follow-up. The prevalence of any liver disease was 10% (n = 155). Liver cirrhosis was found in 7% of the individuals (n = 116) and hepatocellular carcinoma in 2% (n = 29). The mean age at the onset of liver disease was 61 (SD 15) years. In multivariate analyses, the male gender, age over 50 years, repeated elevated LFTs, hepatitis virus infection, and a diagnosis of diabetes were associated with increased risk of developing liver disease in adulthood (p < 0.01). CONCLUSION: The prevalence of liver disease in adult PiZZ individuals is 10%. Age over 50 years, the male gender, repeated elevated liver enzymes, hepatitis, and the presence of diabetes mellitus are risk factors for developing liver disease.