Show-Me State Times

Saint Louis University researchers have identified biomarkers in infants with alpha-1 antitrypsin deficiency (AATD), a condition that can be life-threatening. The study, published in Gastro Hep Advances, suggests that circulating Z polymer levels can indicate which infants are likely to develop severe liver disease.

Jeffrey Teckman, M.D., a professor at Saint Louis University and senior author of the study, stated, “These data will allow identification of a group of infants at high risk of severe disease soon after diagnosis.” Teckman is recognized as an authority on AATD, a genetic disorder affecting one in 3,500 people. The condition has over 100 variants and can lead to lung and liver diseases.

Symptoms of AATD include shortness of breath, wheezing, lung infections, yellow skin, fatigue, cirrhosis, portal hypertension (CEPH), liver failure, and potentially death. Currently, the only treatment is a liver transplant. Despite significant progress in developing new therapies for AATD in recent years, no treatments have been approved yet.

The discovery of these biomarkers is expected to advance pediatric clinical trials by focusing on high-risk infants. Teckman explained that this would help avoid unnecessary trials for many participants and accelerate effective treatments' approval process. “Enrollment of children into trials can then be focused on this high-risk group,” he added.

Data was collected by the Childhood Liver Disease Research Network (ChiLDReN), supported by the National Institutes of Health (NIH). Seventeen consortium centers gathered data during the study period to understand pediatric liver diseases better. Researchers measured ZZ AAT serum polymer levels from samples collected between 2007 and 2015.

The analysis showed that higher Z polymer levels were associated with existing CEPH and predicted future CEPH in childhood among infants without it initially. Total AAT was not predictive. In early life stages, gamma-glutamyl transpeptidase (GGT) was also linked to future CEPH.

Teckman and his team developed a model combining GGT and polymer levels to identify those at high risk for future CEPH. Co-authors include Paula Buchanan from Saint Louis University School of Medicine; Keith Steven Blomenkamp from SSM Health Cardinal Glennon Children's Hospital; Keith Burling from Cambridge University Hospitals NHS Foundation Trust; Nina Heyer-Chauhan and David A Lomas from University College London.

Teckman's research received support from ChiLDReN: NIH grants DK 62453 and UL1 TR002535 through subcontracts with the University of Colorado Denver and Children’s Hospital Colorado; the Alpha-1 Foundation; Saint Louis University Liver Center; Cardinal Glennon Children’s Hospital Foundation.