Treatment of Liver Disease in Alpha-1 Antitrypsin Deficiency
Liver transplantation is the only definitive treatment for advanced liver disease in alpha-1 antitrypsin deficiency, as no specific medical therapy exists and intravenous augmentation therapy does not benefit the liver. 1, 2
No Medical Therapy Available
- There is currently no specific medical therapy for alpha-1 antitrypsin deficiency-related liver disease 1, 2
- Intravenous augmentation therapy with α1-antiprotease, while used for lung disease, does not confer any benefits for liver disease and should not be used for this indication 1, 2
- Management consists entirely of supportive care for complications of chronic liver disease 3
Supportive Management
For patients with compensated or slowly progressive disease, focus on:
- Hepatitis A and B vaccinations to prevent additional liver injury 1, 2
- Regular monitoring with physical examination, liver function tests, and ultrasound examination 1, 2
- Management of complications including gastrointestinal bleeding, ascites, edema, encephalopathy, coagulopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome 3
- Treatment of cholestatic symptoms when present: pruritus, hypercholesterolemia, and fat-soluble vitamin deficiencies 3
Surveillance for Hepatocellular Carcinoma
In patients ≥50 years old with decompensated cirrhosis:
- Perform periodic CT imaging of the liver for hepatocellular carcinoma surveillance 1, 2
- Do not rely on α-fetoprotein measurement alone, as it has poor sensitivity 1
- Men with alpha-1 antitrypsin deficiency have increased risk for hepatocellular carcinoma 1
Liver Transplantation Indications
Refer for liver transplantation evaluation when:
- Decompensated cirrhosis develops (ascites, variceal bleeding, encephalopathy, synthetic dysfunction) 1
- Progressive liver dysfunction occurs despite supportive care 3
- Manifestations of liver disease interfere with overall life functioning, even in patients with nonprogressive disease 3
Do not delay referral based solely on:
- Presence of compensated cirrhosis alone 3
- Mild portal hypertension without decompensation 3
- Mild synthetic dysfunction if stable 3
Transplant Outcomes
Liver transplantation provides excellent results:
- In children: 1-year survival 94%, 5-year survival 92% 1
- In adults: 1-year survival 88%, 3-year survival 84% 1
- Five-year survival exceeds 90% in children and 80% in adults 4
- Transplantation is curative and corrects the metabolic defect 5
Special Pediatric Considerations
- Alpha-1 antitrypsin deficiency is the most common inherited cause of liver transplantation in children 1
- Seven percent of children with PI*ZZ phenotype develop cirrhosis, with 16.5% requiring transplantation in childhood 4
- Most children with neonatal cholestasis have spontaneous resolution, but 25% develop cirrhosis within the first decade 1
- Early referral to a liver transplant center reduces waiting time and improves outcomes 6
Critical Pitfalls to Avoid
- Do not use augmentation therapy for liver disease – it only benefits lung disease, not hepatic manifestations 1, 2
- Do not perform liver biopsy for diagnosis – it is only useful for staging established liver disease 1, 2
- Do not delay transplant referral until end-stage disease – refer when decompensation begins or quality of life deteriorates 3
- Do not assume all PI*ZZ patients will develop severe liver disease – only 10-15% develop clinically significant hepatic involvement 1
Emerging Therapies
Research is focused on preventing conformational abnormalities and polymer formation through chemical chaperones, gene therapy, and small molecule therapies, but none are currently approved for clinical use 1, 5, 7