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Screening for AATD-LD
Screening for Alpha-1 Antitrypsin Deficiency Liver Disease: Call to Action

Released: August 28, 2024

Expiration: August 27, 2025

Pavel Strnad
Pavel Strnad, MD
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Key Takeaways
  • Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that significantly affects both lung and liver health. Screening is crucial, as AATD is more common than many healthcare professionals realize, and early detection can lead to beneficial lifestyle changes and improved treatment outcomes.
  • Expanding screening is imperative for AATD, especially in patients with potential liver disease. Because of the lack of specific clinical signs, healthcare professionals must consider AATD in a wide range of patients, regardless of coexisting conditions.

Alpha-1 antitrypsin deficiency (AATD) is an inherited condition whose impact on the liver has been underappreciated for a long time. Although many healthcare professionals (HCPs) are aware of AATD as a lung disease—largely because of the availability of intravenous AAT therapy to treat emphysema caused by severe forms of AATD and related recommended screening initiatives—the liver-related consequences of AATD have not received the same level of attention. This oversight is significant because liver disease is the second leading cause of death in patients with AATD, following lung disease.

One of the challenges in recognizing AATD associated liver disease (AATD-LD) is the independent development of lung and liver manifestations. A patient may have severe liver disease with no lung involvement, or vice versa, making it imperative to simultaneously look for both. Further compounding the issue, patients with AATD may be overlooked as the symptoms share many overlaps with other common lung and liver disorders. Moreover, AATD is more common than many HCPs realize, with an estimated 3.4 million individuals with AATD. Severe AATD is associated with the PiZZ genotype, with 95% of cases linked to this genotype. The PiZZ genotype decreases serum AAT levels to 15% of the normal value and affects approximately 1 in 3000 individuals in North America, making it one of the most common potentially lethal genetic liver disorders further highlighting the need for screening.

Beyond the necessity of diagnosis, screening for AATD-LD offers patients the opportunity to participate in clinical trials for emerging therapies. Lately, there has been a lot of attention on new drug candidates for this space. Identifying AATD early also can help patients manage their condition more effectively, as they will have the opportunity to make lifestyle adjustments to reduce risk factors for liver disease, such as avoiding hepatotoxic substances, reducing alcohol consumption, and losing weight or maintaining a healthy weight. Smoking cessation is the key life-prolonging intervention. Early awareness of AATD gives patients the opportunity to do the best with the genetic cards they have been dealt.

The Role of Genetic Counseling and Screening Families for AATD

It is important to acknowledge that AATD is a genetic disorder with implications that extend beyond the individual patient. Some patients may have family members who may be unknowingly affected or may have family members who died from lung or liver disease without knowing why. Even if family members, including children, are not showing symptoms, they could still be at risk. The presence of AATD in one family member necessitates consideration of the entire family’s health because of the inherited nature of the condition.

Genetic counseling helps families understand the risks and make informed decisions about monitoring and lifestyle adjustments. Given that AATD can manifest differently across individuals, including children who may not show signs of the disease, early detection through family screening can be lifesaving. This approach ensures that interventions can be incorporated early, potentially preventing the development or progression of liver or lung disease in these relatives.

Current Status of Screening for AATD-LD

Current recommendations for screening include all patients with chronic obstructive pulmonary disease(COPD) regardless of age or ethnicity; all individuals with unexplained liver disease; all individuals with necrotizing panniculitis, granulomatosis with polyangiitis, or unexplained bronchiectasis; and family members of individuals who have an abnormal AAT genotype. Collaborating with well-organized patient advocacy groups and pulmonologists has significantly increased referrals and awareness of the importance of screening. However, even with heightened awareness, challenges remain, particularly in conducting comprehensive liver screening.

Liver disease often progresses silently, with significant fibrosis or cirrhosis becoming clinically apparent only in advanced stages. Unlike lung disease, which often presents with more obvious symptoms like shortness of breath, early liver disease symptoms can be vague and nonspecific, such as fatigue or mild itching. This subtlety makes it easy for liver disease to go unnoticed until it reaches a more severe state. Moreover, AATD may coexist with other liver comorbidities or risk factors such as obesity, diabetes, or risky alcohol consumption.

The difficulty in measuring liver fibrosis—a key indicator of liver damage—further complicates screening efforts. Although lung disease in patients with AATD is more readily identified because of symptomatic presentation, liver involvement requires more deliberate and systematic screening to catch the disease before it advances too far.

A Call to Action: A Need to Close Gaps in Screening for AATD-LD

A significant gap in the current screening practices for AATD-LD is the need for a more expanded approach. It is estimated that fewer than 10% of patients with AATD are diagnosed. Too many patients are diagnosed only when having a decompensated liver cirrhosis that carries a very poor prognosis. Given that AATD can present without a clear pattern and may coexist with other conditions such as COPD, obesity, diabetes, or moderate alcohol use, it is critical to rule out AATD in all patients with existing lung or liver disease in addition to those with risk factors for these conditions. There is no single clinical indicator that definitively indicates AATD, making it essential to screen broadly rather than relying on specific symptoms.

In some cases, patients with AATD may not have lung disease, or they might present with other rare conditions associated with AATD, such as folliculitis or certain types of vasculitis. However, these conditions are not always present, reinforcing the need for comprehensive screening whenever liver disease is suspected. Without this thorough approach, AATD can be easily missed, leading to delayed diagnosis and treatment.

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