From the Guidelines
Liver transplantation is the definitive treatment for patients with alpha-1 antitrypsin (A1AT) deficiency who have developed end-stage liver disease, as it effectively cures the liver manifestations of A1AT deficiency by replacing the organ that produces the defective protein. This recommendation is based on the most recent and highest quality evidence available, which suggests that liver transplantation has excellent outcomes for patients with A1AT deficiency, with 5-year survival rates exceeding 80% 1. The decision to proceed with liver transplantation should be made on a case-by-case basis, taking into account individual factors such as the severity of liver disease, the presence of complications, and the patient's overall health status.
Indications for Liver Transplantation
The indications for liver transplantation in patients with A1AT deficiency include:
- Decompensated cirrhosis, characterized by complications such as ascites, variceal bleeding, hepatic encephalopathy, or hepatocellular carcinoma
- Significant disease progression, as indicated by a Model for End-Stage Liver Disease (MELD) score above 15
- Presence of portal hypertension, elevated serum transaminases, or prolongation of prothrombin time, which may remain stable for many years without the need for liver transplantation, but require careful monitoring and evaluation for transplantation 1
Post-Transplantation Management
Post-transplantation, patients require lifelong immunosuppression therapy, typically including:
- Tacrolimus or cyclosporine
- Mycophenolate mofetil
- A tapering course of corticosteroids This therapy is essential to prevent rejection of the transplanted liver and ensure long-term survival.
Outcomes and Quality of Life
Liver transplantation for A1AT deficiency has excellent outcomes, with 5-year survival rates exceeding 80% 1. The success of this approach stems from addressing the root cause of liver damage—the accumulation of abnormal A1AT protein within hepatocytes—by replacing the organ that produces the defective protein. However, it's essential to note that while liver transplantation resolves the liver disease, patients with concurrent lung disease may still require ongoing pulmonary management, as existing lung damage is not reversed by transplantation.
From the Research
Role of Liver Transplantation in Alpha 1 Antitrypsin Deficiency
- Liver transplantation is the only treatment option available for patients with alpha 1 antitrypsin (A1AT) deficiency and severe liver disease, such as cirrhosis and hepatocellular carcinoma 2, 3, 4.
- The procedure can improve patient survival rates, with overall cumulative patient survival rates post-transplant ranging from 86% to 97.8% at 1 year, and 72% to 95.5% at 5-10 years 3, 5.
- Liver transplantation can also normalize AAT serum levels, halting further lung and liver disease progression, as the AAT phenotype of the recipient becomes that of the donor 2, 5.
- However, post-liver transplant respiratory function may continue to decline in line with normal age-related lung function decline, and monitoring of lung function is essential, especially in adults 2, 4, 5.
Outcomes of Liver Transplantation for A1AT Deficiency
- Studies have reported excellent patient and graft survival rates after liver transplantation for A1AT deficiency, with overall cumulative graft survival rates ranging from 81.5% to 92.2% at 1-20 years 3, 5.
- The majority of patients undergoing liver transplantation for A1AT deficiency have the PI*ZZ genotype/phenotype, and the procedure can cure cirrhosis caused by A1AT deficiency and restore normal production of AAT 3, 5.
- However, there is a high variability in clinical disease presentation, suggesting that environmental and genetic modifiers are important, and management of A1AT liver disease is based on standard supportive care and liver transplant 6.