Accumulation of hepatitis B surface antigen promotes the development of alpha-1 antitrypsin mutation-related liver disease

Introduction: α1-antitrypsin (AAT) constitutes the major serum protease inhibitor that is produced predominantly in hepatocytes. An AAT mutation termed PiZ leads to its polymerization and retention in the endoplasmic reticulum (ER) thereby causing the development of AAT deficiency, the third most common lethal genetic condition in humans. While up to 40% of PiZZ patients develop liver cirrhosis, the phenotype of the disease is highly variable and the factors contributing its development remain unknown. Aims & methodology: To mimic the consequences of a hepatitis B (HBV) infection-related ER stress, we crossbred…