Baseline Analysis of a Young α-1-Antitrypsin Deficiency Liver Disease Cohort Reveals Frequent Portal Hypertension

Abstract

Objectives: α-1-Antitrypsin (A1AT) deficiency is a common genetic disease with an unpredictable and highly variable course. The Childhood Liver Disease Research and Education Network is a National Institutes of Health, multicenter, longitudinal consortium studying pediatric liver diseases, with the objective of prospectively defining natural history and identifying disease modifiers.

Methods: Longitudinal, cohort study of A1AT patients' birth through 25 years diagnosed as having liver disease, type PIZZ or PISZ. Medical history, physical examination, laboratory, imaging, and standardized survey tool data were collected during the provision of standard of care.

Results: In the present report of the cohort at baseline, 269 subjects were enrolled between November 2008 and October 2012 (208 with their native livers and 61 postliver transplant). Subjects with mild disease (native livers and no portal hypertension [PHT]) compared to severe disease (with PHT or postliver transplant) were not different in age at presentation. A total of 57% of subjects with mild disease and 76% with severe disease were jaundiced at presentation (P = 0.0024). A total of 29% of subjects with native livers had PHT, but age at diagnosis and growth were not different between the no-PHT and PHT groups (P > 0.05). Subjects with native livers and PHT were more likely to have elevated bilirubin, ALT, AST, INR, and GGTP than the no-PHT group (P << 0.001), but overlap was large. Chemistries alone could not identify PHT.

Conclusions: Many subjects with A1AT presenting with elevated liver tests and jaundice improve spontaneously. Subjects with PHT have few symptoms and normal growth. Longitudinal cohort follow-up will identify genetic and environmental disease modifiers.

Trial registration: ClinicalTrials.gov NCT00571272.

Figure 1. Age at diagnosis of the mild versus severe liver disease patients

Relationship of age in years on the horizontal axis versus number of patients (N) at a given age at diagnosis on vertical axis for mild liver disease patients (left panel) and severe liver disease patients (right panel).

Figure 2. AST and GGTP Levels by PHT Status

AST and GGTP levels in U/L on the vertical axis for groups with PHT absent or present. Mean values bold line, box 25^th-75^th quartiles (two points from the PHT Absent group [1005 and 2443 u/l] and two points from the PHT Present group [1566 and 1786 u/l] do not appear on this graph).