Alpha-1-Antitrypsin PiMZ variant increases risk of developing hepatic events in nonalcoholic fatty liver disease patients

•Pi*MZ variant is an independent predictor of development of hepatic decompensation events in patients with NAFLD.•Clinicians should consider testing for alpha-1-antitrypsin phenotype in NAFLD patients.•Patients with NAFLD & Pi*MZ should be counseled about increased risk of hepatic decompensation and offered aggressive interventions . Heterozygous alpha-1-antitrypsin (A1AT) Pi*MZ variant has been shown to increase the risk of developing liver cirrhosis in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to determine the association between heterozygous Pi*MZ and Pi*MS variants and development of hepatic decompensation events in NAFLD patients. We included patients with NAFLD who also had A1AT genotyping performed from 2005 to 2020. We recorded demographic and clinical variables, and data on hepatic events (ascites, hepatic encephalopathy, esophageal variceal bleed, or hepatocellular carcinoma), if any. We performed binary logistic regression analysis to assess the association between A1AT variants and hepatic events, and calculated Odds ratio (OR) with their 95% confidence intervals (Cl). We included 1532 patients with NAFLD, of which 1249 patients had Pi*MM, 121 had Pi*MS, and 162 had Pi*MZ. Of the 1532 patients, hepatic events developed in 521 (34%) patients. The percentage of patients with Pi*MZ variant was significantly higher in patients with hepatic events as compared to patients without hepatic events (18.7 % vs 8.1%, p