Lung and liver transplantation in patients with alpha-1 antitrypsin deficiency

Abstract

Alpha-1 antitrypsin (AAT) augmentation is effective in slowing the progression of emphysema due to AAT deficiency (AATD) but cannot prevent eventual progression to end-stage lung disease and complete respiratory failure, which is the leading cause of death for individuals with severe AATD. When patients develop end-stage lung disease, lung transplantation is the only treatment option available, and this can improve lung physiology and patient health status. The available data suggest that survival rates for lung transplantation are significantly higher for patients with AATD-related chronic obstructive pulmonary disease (COPD) compared with non-AATD-related COPD, but, conversely, there is a higher risk of common post-lung transplant complications in patients with AATD versus non-AATD COPD. Nevertheless, lung transplantation (single and bilateral) is favorable for patients with AATD. After respiratory failure, the second leading cause of death in patients with AATD is liver disease, for example, cirrhosis and hepatocellular carcinoma, caused by the accumulation of mutant forms of AAT retained within the liver. As with lung disease, the only treatment option for end-stage liver disease is liver transplantation. Survival rates for patients with AATD undergoing liver transplantation are also favorable, and patients, particularly pediatric patients, have benefitted from advancements in peri-/post-surgical care. As the majority of AAT is produced by the liver, the AAT phenotype of the recipient becomes that of the donor, meaning that AAT serum levels should be normalized (if the donor is AAT-replete), halting further lung and liver disease progression. However, post-liver transplant respiratory function may continue to decline in line with normal age-related lung function decline. In the most severe cases, where patients have simultaneous end-stage lung and liver disease, combined lung and liver transplantation is a treatment option with favorable outcomes. However, there is very little information available on this procedure in patients with AATD.

Keywords: alpha-1 antitrypsin; alpha-1 antitrypsin deficiency; combined lung and liver transplant; liver transplant; lung transplant; post-transplant survival.

Figure 1.

Survival following lung transplantation is decreased in the short-term but increased in the long-term in patients with AATD versus non-AATD-related COPD. Reproduced with permission from Spratt et al. AAT, alpha-1 antitrypsin; AATD, AAT deficiency; COPD, chronic obstructive pulmonary disease.

Figure 2.

Liver transplantation is associated with high long-term survival rates in both adult and pediatric patients with AATD. Reproduced with permission from Kemmer et al. AAT, alpha-1 antitrypsin; AATD, AAT deficiency.