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The following is a summary of the study, “Longitudinal evaluation of individuals with severe alpha-1 antitrypsin deficiency (Pi*ZZ genotype),” published online in Gastroenterology in October 2024 by Fromme et al.

Alpha-1 antitrypsin deficiency, particularly in individuals with the Pi*ZZ genotype, predisposes patients to both pulmonary and hepatic damage. For a study, a team of researchers aimed to evaluate the natural progression of the disease and identify key indicators that predict liver and lung outcomes in individuals with this severe genetic condition, which could help refine participant selection for clinical trials targeting either the liver or the lungs.

The study involved two cohorts. Cohort 1 included 737 individuals with Pi*ZZ from 25 international centers. These participants, who had no known liver comorbidities, underwent baseline clinical assessments, laboratory tests, and liver stiffness measurements (LSM), with follow-up interviews conducted after six months. Cohort 2 involved 135 individuals with Pi*ZZ without significant liver fibrosis who were examined at baseline and again at least two years later with standardized assessments and LSM.

Over 2,634 patient-years of follow-up, 39 participants died, with liver-related and lung-related issues accounting for 46% and 36% of deaths, respectively. Individuals with Pi*ZZ who developed liver-related complications showed significantly elevated baseline liver fibrosis indicators, including higher LSM (24 vs. 5 kPa, p<.001) and AST-to-platelet ratio index (APRI, 1.1 vs. 0.3 units, p<.001). Within five years, liver stiffness measurement was the strongest predictor of liver-related outcomes (AUC 0.95), followed closely by APRI (AUC 0.92). Lung function parameters, such as FEV1, showed only moderate predictive value for lung-related endpoints (AUC 0.76). Fibrosis progression was rare in individuals with no or mild fibrosis at baseline and was largely limited to those with preexisting risk factors.

The study concludes that non-invasive liver fibrosis markers, such as LSM and APRI, are highly effective in predicting liver-related risks in individuals with Pi*ZZ. These findings are expected to inform routine care and improve participant selection for future clinical trials aimed at addressing liver and lung complications in patients with alpha-1 antitrypsin deficiency.

Source: sciencedirect.com/science/article/pii/S0016508524055720