Longitudinal Evaluation of Individuals With Severe Alpha-1 Antitrypsin Deficiency (Pi∗ZZ Genotype) - New ERN Paper in Gastroenterology

The severe alpha-1 antitrypsin deficiency (AATD) (Pi*ZZ genotype) predisposes to pulmonary loss-of-function and hepatic gain-of-function injury. To improve the clinical management of Pi*ZZ subjects, we put together an international, ERN-associated, multicenter, longitudinal Pi*ZZ cohort evaluating the natural disease course and surrogates for future liver- and lung-related endpoints. During 2634 follow-up years, 39 individuals died, with liver and lung being responsible for 46% and 36% of deaths, respectively. Liver-related endpoints within five years were most accurately predicted by LSM (area under the curve [AUC] 0.95) followed by APRI (0.92). Baseline lung parameters displayed only a moderate predictive utility for lung-related endpoints within five years (FEV1 AUC 0.76). Fibrosis progression in those with no/mild fibrosis at baseline was rare and primarily seen in those with preexisting risk factors. Overall, the comparison of liver and lung surrogated should facilitate patient management as well as selection into clinical trials that typically target only one organ.

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