Author
Malin Fromme, Christina Schrader and Pavel Strnad for the Alpha1 liver team from Aachen, as published in Alpha1 Journal 2/2024.
Dear Alphas,
Over the past few years, we have performed liver examinations on many of you, and most of you have also been contacted by phone or mail recently to fill out a questionnaire with us.
The aim was to monitor the progression of alpha-1 antitrypsin deficiency (AATD)-associated liver and lung disease and to evaluate how well our non-invasive liver fibrosis tests (such as FibroScan) can predict the development of life-threatening liver disease (e.g., transplantation or decompensation of liver cirrhosis). The corresponding results have now been published in the journal Gastroenterology.
https://pubmed.ncbi.nlm.nih.gov/39414159/
In this study, 737 participants with the homozygous genotype Pi*ZZ were followed for an average of 3.5 years; 25 European centers participated. A total of 39 participants died, with liver and lung disease being the main causes of death. Among the 41 individuals who developed life-threatening liver disease, it was shown that they had already exhibited significantly higher non-invasive liver fibrosis test results at the initial baseline examination.
Encouragingly, our liver fibrosis tests (e.g., FibroScan and AST-to-platelet index/APRI) also demonstrated excellent predictive power for these liver endpoints. Not a single patient with an initial FibroScan value below 7.1 kPa developed life-threatening liver disease during the entire follow-up period, whereas the risk increased with rising liver stiffness. In contrast to our non-invasive liver fibrosis tests, surrogate markers of lung function (e.g., FEV1) showed only moderate predictive power for lung endpoints (such as transplantation or lung-related death).
Overall, these results help us to better assess the individual risk of AATM-associated liver and lung disease and to perform accurate risk stratification. This is essential not only for clinical care but also for ongoing drug trials to enable tailored treatment.
Another longitudinal project currently being conducted by the Alpha1 Liver Center in Aachen is a metabolic study evaluating the significance of metabolic risk factors, such as obesity and diabetes mellitus, in patients with the Pi*ZZ genotype. While finalization and publication of the results are still underway, preliminary analyses show clear findings. The presence of diabetes mellitus was associated with an approximately sixfold increased risk of developing life-threatening liver disease. Similar trends are also evident in Pi*ZZ patients with obesity – the risk in these patients was about four times higher than in patients of normal weight. These results underscore once again the importance of a healthy lifestyle with a balanced diet and sufficient exercise for liver health. At the same time, they indicate that patients with additional risk factors require closer monitoring.
We would like to express our sincere gratitude for your cooperation and participation in the study. Without you, this study, which provides us with such important results for the management of "alphas" in the clinic and contributes to continuously improving care, would not have been possible! THANK YOU VERY MUCH! Please feel free to contact us if you have any further questions.
