AATD

• Alpha-1 antitrypsin deficiency is a rare autosomal recessive disorder that causes liver and pulmonary disease.
• Alpha-1 antitrypsin (AAT) is an abundant enzyme found within the body. It is produced in the liver and acts as a protease inhibitor. It is important in the inhibition of neutrophil elastase. Neutrophil elastase acts by damaging bacteria, but unchecked, it can lead to lung damage.
• Alpha-1 antitrypsin deficiency (AATD) refers to a lack of circulating AAT due to mutations that prevent it from being released from hepatocytes. This has knock-on effects in the liver and lungs.

  • Liver: build up in hepatocytes. This can cause chronic damage leading to cirrhosis.
  • Lungs: absent inhibition of neutrophil elastase. This causes lung damage leading to chronic obstructive airway disease (COPD).
• AATD is characterised by development of COPD and chronic liver disease.
• Pulmonary clinical features

  • Dyspnoea
  • Cough
  • Wheeze
  • Ankle swelling (right-sided heart failure from chronic lung disease)
• Hepatic clinical features

  • Jaundice
  • Bruising
  • Spider naevi
  • Palmar erythema
  • Hepatomegaly
  • Ascites
  • Leuconychia
  • Confusion
  • Asterixis: flapping tremor (suggests encephalopathy)
  • Cachexia
• Indications for AATD testing:

  • COPD: particularly early onset (≤ 45 years) and non-smokers
  • Chronic liver disease
  • Family history of COPD and/or liver disease
  • Adult onset asthma with poor response to bronchodilators
• Serum alpha-1-antitrypsin levels form the first line investigation for AATD.
• Patients with evidence of low AAT levels can have gene testing to look for the most common mutations (i.e. Z and S).
• Other investigations:

  • Pulmonary function tests: looking for airflow obstruction typical of COPD.
  • Pulmonary Imaging: chest x-ray and CT chest. Emphysema in AATD is typically located in the lower zones (i.e. basal regions) with panacinar involvement.
  • Liver imaging: liver ultrasound is a simple non-invasive test that can be used to look for chronic liver disease and portal hypertension.
• The management of AATD is supportive and treatment follows the usual guidelines for the management of COPD and chronic liver disease.
• Patients with established cirrhosis need regular surveillance for hepatocellular carcinoma with 6-monthly liver ultrasound and alpha-fetoprotein (AFP) monitoring.
• Patients with severe lung or liver disease may be considered for transplantation. This is highly specialist and requires referral for assessment at a tertiary centre. Other treatment options include long-term oxygen therapy (LTOT) and lung volume reduction surgery.
• Trials are ongoing into the use of intravenous human alpha-1-antitrypsin therapy (e.g. Zemaira) to treat AATD. However, in the UK this is currently not recommended by NICE