Synopsis
Identify alpha-1 antitrypsin deficiency across liver and lung phenotypes, confirm genotype and prevent avoidable cofactors while staging complications.
- Alpha-1 antitrypsin is produced mainly by hepatocytes and protects lung connective tissue from neutrophil elastase.
- The common Z variant misfolds and polymerises within hepatocytes, causing toxic gain-of-function liver injury while low circulating protein creates loss-of-function lung risk.
- Severe Pi*ZZ disease can present as neonatal cholestasis, childhood fibrosis or adult cirrhosis and hepatocellular carcinoma, with widely variable penetrance.
Key red flags
Prolonged conjugated jaundice, hepatomegaly, pale stool, poor growth or coagulopathy occurs in infancy after urgent obstructive and metabolic causes are considered.
Investigation priorities
Screen for reduced circulating protein in unexplained liver or early lung disease.
Management branches
A1AT is low or clinical suspicion remains despite a borderline concentration.
- Check CRP, liver synthesis and protein-loss context and repeat a potentially inflammation-confounded concentration when appropriate.
- Request phenotype or common SERPINA1 genotyping under the current NHS pathway and seek broader analysis if results do not explain the level or phenotype.
Key medicines
Licensed smoking-cessation pharmacotherapySelect nicotine replacement, varenicline, cytisinicline or another current NICE-supported option at its BNF regimen according to dependence, contraindications, pregnancy and local service availability, combined with behavioural support.
Inhaled COPD therapyUse short- and long-acting bronchodilator or inhaled corticosteroid combinations only according to the current NICE NG115 symptom, exacerbation and spirometry pathway, with inhaler teaching and review.