Metabolic liver disease: Alpha 1 antitrypsin disease

Question 1

Defintion

Answer 1

Alpha-1 antitrypsin (A1AT) is a protease inhibitor made in the liver which predominantly acts to protect the lungs from neutrophil elastase. Deficiency in this leads to decreased elastin = decreased elasticity and stucture of the alveoli leading to pan acinar emphysema

Question 2

Epidemiology

Answer 2

European ancestry
* uncommon in people of Asian descent *
Age 32 - 41
Male

Question 3

Risk factors

Answer 3

Family history: there may be a family history of early-onset COPD

Question 4

Aetiology

Answer 4

Deficiency in A1AT, resulting in protease-mediated damage, particularly in the lungs
- mutation is located on chromosome 14 and is inherited in an autosomal recessive/co-dominant fashion.

Question 5

Signs and symptoms

Answer 5

Respiratory
- Dyspnoea and productive cough
- Prolonged expiratory phase and wheeze with pursed-lip breathing
- Weight loss
- Barrel chested due to hyperexpanded lungs
Liver
- Jaundice
- Hepatomegaly
- Ascites

Question 6

Characteristic Px

Answer 6

Young/Middle aged man with little to no smoking history + with COPD like symptoms

Question 7

Diagnosis

Answer 7

A1AT deficiency should be considered in any young patient presenting with chronic liver or respiratory disease.
- Serum A1AT < 20mmol/L
- Barrel shaped chest on exam - CXR shows hyperinflated lungs
- CT = pan-acinar emphysema
- LFT = spirometry shows OBSTRUCTION (FEV1:FVC <0/7)
- Genetic testing = +ve SERPINA 1 gene mutation

Question 8

Treatment

Answer 8

Smoking cessation
Manage emphysema e.g. inhalers (SABAs, LAMAs)
Consider hepatic decompensation patients for Liver transplant

Question 9

Complications

Answer 9

Respiratory failure: much like COPD, these patients are at risk of respiratory failure, particularly type 2 respiratory failure
Cirrhosis
Hepatocellular carcinoma
Cholestasis: usually in children