Prevalence of liver disease and liver transplantation in pediatric ZZ alpha-1 antitrypsin deficiency: a systematic review and meta-analysis
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background
Pediatric Pi*ZZ alpha-1 antitrypsin deficiency (A1ATD) can cause hepatocyte A1AT polymer retention and progressive liver injury, but estimates of childhood liver morbidity vary across studies and remain poorly defined.
Aim
To quantify liver-specific outcomes in pediatric Pi*ZZ A1ATD.
Methods
We systematically reviewed studies reporting liver-specific outcomes in children with confirmed Pi*ZZ/ZZ A1ATD (PROSPERO CRD42022335666). We extracted prevalence of fibrosis and cirrhosis, elevated liver enzymes, and liver transplantation. Random-effects meta-analysis pooled logit-transformed proportions (with sensitivity analyses assessing robustness to model assumptions).
Results
Thirteen studies including 398 children met inclusion criteria. Pooled prevalence was 41.3% (95% CI 29.6–54.0) for fibrosis and 17.3% (7.2–35.9) for cirrhosis, with substantial heterogeneity for cirrhosis (I2 78.6%). Liver transplantation prevalence was 10.7% (6.3–13.0). Elevated liver enzymes occurred in 43.0% (19.2–70.5) with high heterogeneity (I2 89.4%). Across cohorts, the proportion with elevated liver enzymes declined with increasing mean age, despite ongoing liver disease in reported histology-based outcomes.
Conclusions
Clinically important liver disease occurs in a substantial subset of children with Pi*ZZ A1ATD. Declining rates of elevated liver enzymes with age should not be interpreted as disease resolution. Standardized registries are needed for longitudinal surveillance, to identify disease modifiers, and to guide early intervention in this high-risk population.
Pediatric Pi*ZZ alpha-1 antitrypsin deficiency (A1ATD) can cause hepatocyte A1AT polymer retention and progressive liver injury, but estimates of childhood liver morbidity vary across studies and remain poorly defined.
Aim
To quantify liver-specific outcomes in pediatric Pi*ZZ A1ATD.
Methods
We systematically reviewed studies reporting liver-specific outcomes in children with confirmed Pi*ZZ/ZZ A1ATD (PROSPERO CRD42022335666). We extracted prevalence of fibrosis and cirrhosis, elevated liver enzymes, and liver transplantation. Random-effects meta-analysis pooled logit-transformed proportions (with sensitivity analyses assessing robustness to model assumptions).
Results
Thirteen studies including 398 children met inclusion criteria. Pooled prevalence was 41.3% (95% CI 29.6–54.0) for fibrosis and 17.3% (7.2–35.9) for cirrhosis, with substantial heterogeneity for cirrhosis (I2 78.6%). Liver transplantation prevalence was 10.7% (6.3–13.0). Elevated liver enzymes occurred in 43.0% (19.2–70.5) with high heterogeneity (I2 89.4%). Across cohorts, the proportion with elevated liver enzymes declined with increasing mean age, despite ongoing liver disease in reported histology-based outcomes.
Conclusions
Clinically important liver disease occurs in a substantial subset of children with Pi*ZZ A1ATD. Declining rates of elevated liver enzymes with age should not be interpreted as disease resolution. Standardized registries are needed for longitudinal surveillance, to identify disease modifiers, and to guide early intervention in this high-risk population.
Date Issued
2026-05-01
Date Acceptance
2026-02-08
Citation
Digestive and Liver Disease, 2026, 58 (5), pp.608-613
ISSN
1590-8658
Publisher
Elsevier
Start Page
608
End Page
613
Journal / Book Title
Digestive and Liver Disease
Volume
58
Issue
5
Copyright Statement
© 2026 The Authors. Published by Elsevier B.V. on behalf of Editrice Gastroenterologica Italiana S.r.l. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41791905
PII: S1590-8658(26)00290-2
Subjects
Cirrhosis
Liver enzymes
Liver fibrosis
Liver transplantation
Publication Status
Published
Coverage Spatial
Netherlands
Date Publish Online
2026-03-05