Between 50% and 72% of deaths in AAT deficiency are caused by respiratory failure, which comprises a greater percentage of deaths than liver failure.    Evidence suggests the median age of death in AAT deficiency is 40 years in smokers and 65 years in nonsmokers, owing to early-onset emphysema and progressive lung disease.  There is limited evidence assessing the natural history of the disease, but most evaluation of long-term prognosis has been done with regard to pulmonary manifestations of the disease.
FEV1 should be used as a predictor of survival in these patients, as correlation has been established between 2-year mortality and FEV1 >35%.  Rates of decline on FEV1 range from 47 to 80 mL/year in people who have never smoked, 4 to 81 mL/year in ex-smokers, and 61 to 316 mL/year in smokers.    AAT augmentation therapy is effective in slowing radiographic evidence of lung disease, and also in providing mortality benefit.  
Patients who are PI*ZZ and do not manifest pulmonary symptoms are more likely to experience cirrhosis and ultimately liver failure.  Its lifetime prevalence in PI*ZZ individuals is between 10% and 34%.  One third of patients with advanced age and a homozygous phenotype will die of complications related to portal hypertension and primary liver cancer. 
Patients with lung disease require pulmonologist evaluation for any exacerbations of COPD. When well controlled, patients require annual follow-up with spirometry testing in order to assess pulmonary function changes. Affected individuals with liver disease require regular evaluations with liver function tests, whether symptomatic or asymptomatic. 
All patients are urged to undergo hepatitis vaccination and to stop smoking as soon as possible, using pharmacologic assistance if necessary.
Patients with liver disease should be advised to avoid alcohol or at least limit their alcohol intake to <60 g/day (although there is no evidence that ethanol consumption affects progression of disease).