Alpha-1 antitrypsin deficiency is under-recognized in individuals with cirrhosis undergoing liver transplantation

Under-recognition of alpha-1 antitrypsin deficiency (AATD) is well documented in AATD-lung disease but is rarely reported in patients with liver cirrhosis requiring liver transplantation. This report examines the frequency of newly diagnosed AATD based on pathologic examination of explanted livers following liver transplantation, trends in diagnosis over time, and prognostic correlates of under-recognition outcomes following liver transplantation.

This study retrospectively reviewed 1473 pathology reports from adult patients (>18 years) undergoing liver transplantation at Cleveland Clinic between 2004 and 2017. Pathology reports of explanted livers exhibiting periodic acid-Schiff, diastase-resistant inclusion bodies (PAS+G) suggestive of AATD were included and medical records were reviewed regarding demographics, AATD genotype, alternative etiologies for cirrhosis, presence of emphysema, and survival outcomes. Kaplan-Meier estimates of survival outcomes were compared between patients diagnosed pre-liver transplantation and that newly diagnosed post-liver transplantation.

Of 1473 explanted liver pathology reports examined, 117 (7.9%) showed PAS+G suggestive of AATD. The diagnosis of AATD in these 117 patients was established pre-liver transplantation in 36 (30.8%, group 1) and in 46 (39.3%) post-liver transplantation (group 2a). Testing for AATD was not undertaken in 35 (29.9%) of patients despite having PAS+G on explanted livers (group 2b). Post-liver transplantation survival analysis showed a trend (P = 0.098) towards enhanced survival in group 1 vs. group 2 at 10 years.

This study shows that diagnosis of AATD is overlooked and frequently delayed in patients with cirrhosis undergoing liver transplantation. The observed trend towards higher survival in patients diagnosed with AATD pre-liver transplantation suggests the opportunity to enhance outcomes by earlier recognition of AATD.