A Research Guide for Facing Alpha-1 Antitrypsin Deficiency
Understanding Alpha-1, genetic testing, augmentation therapy, lung and liver management, emerging treatments, clinical trials, and practical resources — organized by where you are in the journey.
This guide is not medical advice. It is an educational research summary written in plain language, drawn from published medical literature and clinical trial records. Every important decision must be made together with the patient’s medical team — pulmonologists, hepatologists, and primary care doctors. Nothing here replaces those conversations. The purpose of this guide is to help patients and families walk into those conversations better prepared. This content does not create a doctor-patient relationship. Trouvera’s guides are produced using AI-assisted research synthesis with human editorial review; it is not written by treating physicians. Laws regarding medical information vary by jurisdiction; consult a local licensed professional for advice specific to your situation.
Standard care first. Every option discussed in this guide is intended as an addition to, not a replacement for, evidence-based standard treatments delivered by a qualified pulmonary or hepatology team. Alpha-1 management should be coordinated by physicians experienced with this genetic condition.
If you have unexplained COPD before age 50 or liver disease without an obvious cause, ask about Alpha-1 testing. AATD is severely underdiagnosed — only about 10% of affected individuals have been identified. A simple blood test can change the course of your care.
Content last reviewed: May 2026 · Based on ATS/ERS Statement on Alpha-1 Antitrypsin Deficiency (2003, update pending), Alpha-1 Foundation Clinical Resource Center Guidelines, GOLD 2026 COPD Report, AASLD Practice Guidance, CHEST Guidelines, published clinical trial data, and medical literature · Always verify trial availability and treatment details with your medical team and primary sources.
⚡ Quick Start — If You Read Nothing Else
The 8 most important things to know right now.
Alpha-1 is a genetic condition, not just a lung disease. It is caused by mutations in the SERPINA1 gene that result in low levels of alpha-1 antitrypsin (AAT) protein, which normally protects the lungs from damage. It can also cause liver disease because abnormal AAT protein accumulates in liver cells.
It is massively underdiagnosed. An estimated 100,000 Americans have severe AATD, but only about 10,000 have been diagnosed. The average patient sees 3 or more doctors over 5–7 years before getting the correct diagnosis. If you have early-onset COPD or emphysema, get tested.
A simple blood test can diagnose it. An AAT serum level plus genotyping (or a free home test kit from the Alpha-1 Foundation) is all it takes. Testing should be done once in a lifetime for anyone with COPD, unexplained liver disease, or a family history of Alpha-1.
Augmentation therapy is the only disease-specific treatment for lung disease. Weekly IV infusions of pooled human AAT protein (Prolastin-C, Zemaira, Aralast NP, Glassia) slow the progression of emphysema. It does not reverse existing damage, but it can meaningfully slow decline.
Standard COPD care still applies. Bronchodilators, inhaled corticosteroids (when appropriate), pulmonary rehabilitation, vaccinations, and smoking cessation are essential alongside augmentation therapy.
Smoking is catastrophically harmful for Alpha-1 patients. Smoking accelerates lung destruction dramatically in AATD. If you smoke, stopping is the single most important thing you can do. Even secondhand smoke and occupational exposures should be avoided.
Liver disease requires separate monitoring. About 10–15% of adults with the ZZ genotype develop significant liver disease. Liver function tests should be checked regularly, and hepatology referral is needed if abnormalities arise. Liver transplant is curative for Alpha-1 liver disease.
Promising new therapies are in development. RNA interference (fazirsiran), gene therapy, neutrophil elastase inhibitors, and other approaches are in clinical trials. The treatment landscape may change significantly in the coming years.
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Understanding Alpha-1 Antitrypsin Deficiency
Alpha-1 antitrypsin deficiency (AATD, also called Alpha-1 or AAT deficiency) is a genetic condition that increases the risk of lung disease and liver disease. It is one of the most common serious hereditary conditions in people of European descent, yet it remains severely underdiagnosed.
The condition is caused by mutations in the SERPINA1 gene, which provides instructions for making a protein called alpha-1 antitrypsin (AAT). This protein is produced mainly in the liver and released into the bloodstream, where it travels to the lungs to protect them from damage caused by neutrophil elastase — an enzyme released by white blood cells during normal immune responses and especially during infections.
When AAT levels are too low, neutrophil elastase attacks lung tissue unchecked, gradually destroying the tiny air sacs (alveoli) and leading to emphysema. In some genotypes, the abnormal AAT protein also folds incorrectly and gets stuck inside liver cells, causing liver inflammation, fibrosis, and potentially cirrhosis.
Approximately 100,000 individuals in the US have severe AATD (Pi*ZZ genotype), but only about 10% have been diagnosed
An estimated 3–5 million Americans carry at least one abnormal copy of the SERPINA1 gene (Pi*MZ carriers)
AATD is most common in people of Northern European and Iberian descent
The condition follows an autosomal co-dominant inheritance pattern — both copies of the gene contribute to AAT levels
Average delay from first symptom to diagnosis: 5–7 years
Patients typically see 3 or more physicians before correct diagnosis
Alpha-1 can cause disease through two distinct mechanisms:
Lung disease (loss of function): Low AAT levels in the blood mean inadequate protection for the lungs. Neutrophil elastase progressively destroys lung tissue, leading to emphysema — typically in the lower lobes (unlike smoking-related emphysema, which usually affects the upper lobes). This usually appears between ages 30 and 50, earlier in smokers.
Liver disease (toxic gain of function): Certain AAT mutations (especially the Z mutation) cause the protein to misfold and polymerize inside liver cells. These polymer accumulations trigger inflammation and can lead to fibrosis, cirrhosis, and rarely hepatocellular carcinoma. Liver disease can present in newborns (neonatal hepatitis), children, or adults.
Not everyone with AATD develops both lung and liver disease. Some individuals with the ZZ genotype remain relatively healthy, suggesting that environmental factors and modifier genes play important roles.
The most important concept in this guide: Alpha-1 is a treatable condition. Augmentation therapy can slow lung disease progression. Standard COPD treatments improve symptoms. Liver disease can be monitored and managed. And a new generation of therapies — including RNA interference and gene therapy — is in clinical development. Getting diagnosed is the critical first step.
Key Breakthroughs in Alpha-1
While Alpha-1 research has historically moved more slowly than some other fields, several important advances have changed patient care or are poised to do so:
FDA-APPROVED Augmentation therapy (also called replacement therapy) involves weekly intravenous infusions of purified AAT protein derived from pooled human plasma. The first product, Prolastin, was FDA-approved in 1987. Today, four products are available: Prolastin-C, Zemaira, Aralast NP, and Glassia (the only liquid formulation). The RAPID trial (2015) provided the strongest evidence to date, demonstrating that augmentation therapy significantly slows the rate of lung tissue loss as measured by CT densitometry.
INVESTIGATIONAL Fazirsiran (formerly ARO-AAT) is an RNA interference (RNAi) therapy developed by Arrowhead Pharmaceuticals. It works by silencing the production of mutant Z-AAT protein in the liver, reducing the toxic polymer accumulation that causes liver damage. The SEQUOIA Phase 2 trial showed dramatic reductions in Z-AAT polymer levels, with some patients showing improvement in liver fibrosis, and the Phase 3 REDWOOD trial is now evaluating fazirsiran in patients with ZZ-AATD and liver fibrosis. It remains investigational (not yet FDA-approved), but is currently the most advanced pipeline therapy specifically targeting Alpha-1 liver disease.
INVESTIGATIONAL Alvelestat (MPH966) is an oral neutrophil elastase inhibitor developed by Mereo BioPharma (the molecule originated at AstraZeneca). Rather than replacing AAT protein, alvelestat directly blocks the enzyme that destroys lung tissue. The ASTRAEUS Phase 2 trial showed reductions in desmosine (a biomarker of elastin degradation). Phase 3 trials are being planned. A separate, newer restorative approach — efdoralprin alfa (INBRX-101, developed by Inhibrx and now Sanofi), a recombinant AAT-Fc fusion protein given every 3–4 weeks — met all endpoints in its Phase 2 ElevAATe trial (2025), including higher functional-AAT levels than weekly plasma-derived augmentation. If successful, alvelestat could provide an oral alternative or complement to IV augmentation therapy.
INVESTIGATIONAL A new generation of genetic medicines aims to fix the root genetic problem rather than just replace the missing protein. Several are now in early human trials:
RNA editing — WVE-006 (Wave Life Sciences / GSK): edits the faulty Z-AAT messenger RNA to restore normal M-AAT, with potential to help both the lung and the liver. It produced the first-ever demonstration of RNA editing in people (RestorAATion-2, NCT06405633).
Base editing — BEAM-302 (Beam Therapeutics): a one-time IV, liver-targeted treatment that corrects the Z mutation in the DNA itself (NCT06389877).
Inhaled gene therapy — KB408 (Krystal Biotech): a nebulized vector delivering the SERPINA1 gene directly to the lungs (SERPENTINE-1, NCT06049082).
Older AAV gene-addition approaches (delivering a functional SERPINA1 copy) are also in development. All of these remain investigational and early-stage, but they are the first attempts to correct or silence the underlying genetic defect rather than only replace the protein.
CLINICAL TOOL CT lung densitometry measures the density of lung tissue and can detect emphysema progression years before pulmonary function tests (PFTs) show decline. The RAPID trial validated CT densitometry as a clinically meaningful endpoint for Alpha-1 lung disease, making it possible to demonstrate treatment effects in smaller, shorter trials. This has accelerated clinical development of new therapies.
Diagnosis: Getting Tested for Alpha-1
The ATS/ERS guidelines recommend that all adults with COPD, non-responsive asthma, unexplained liver disease, necrotizing panniculitis, or a family history of Alpha-1 should be tested. Testing is simple and needs to be done only once in a lifetime.
All individuals with COPD or emphysema, regardless of age or smoking history
Adults with asthma that does not fully respond to treatment
Anyone with unexplained liver disease or elevated liver enzymes
Adults with unexplained bronchiectasis
First-degree relatives (parents, siblings, children) of anyone diagnosed with AATD
Individuals with necrotizing panniculitis (a rare skin condition)
Individuals with granulomatosis with polyangiitis (Wegener’s granulomatosis)
A complete Alpha-1 evaluation has three components:
1. AAT serum level: A blood test measuring the amount of AAT protein in the blood. Normal range is 100–300 mg/dL (by nephelometry) or 20–53 µmol/L. Levels below 57 mg/dL (11 µmol/L) are associated with increased risk of emphysema and suggest severe deficiency. Important: AAT is an acute-phase reactant — levels rise during infection, inflammation, or pregnancy, which can mask a deficiency.
2. Genotyping (Pi typing): Identifies the specific SERPINA1 gene variants. Common alleles include M (normal), S (mildly reduced), and Z (severely reduced). The combination determines your phenotype: Pi*MM (normal), Pi*MZ (carrier), Pi*SZ (moderate deficiency), Pi*ZZ (severe deficiency), Pi*Null (no AAT production).
3. Full gene sequencing (if needed): If the serum level is low but genotyping does not explain the result, full SERPINA1 gene sequencing can identify rare or novel mutations not detected by standard isoelectric focusing or targeted genotyping.
Alpha-1 Foundation: Offers free, confidential testing through the Alpha-1 Coded Testing (ACT) Study. A test kit is mailed to your home; you provide a blood sample (finger prick) and mail it back. Results include AAT level and genotype. Request a kit at alpha1.org or call 1-877-228-7321.
Your doctor can order testing through most commercial labs (Quest, LabCorp, ARUP). Many insurance plans cover Alpha-1 testing when ordered for appropriate indications.
Key question for your doctor: “I have COPD/emphysema. Have I ever been tested for Alpha-1 Antitrypsin Deficiency? It requires a blood test done only once in a lifetime.”
Genotypes — What They Mean
Alpha-1 is inherited in an autosomal co-dominant pattern. Each person carries two copies of the SERPINA1 gene — one from each parent. The combination determines AAT production and disease risk.
Genotype
AAT Level
Lung Risk
Liver Risk
What This Means
Pi*MM
Normal (100–300 mg/dL)
None
None
Normal. No Alpha-1 related risk.
Pi*MZ
Mildly reduced (~60% of normal)
Slight increase, especially in smokers
Minimal
Carrier. Generally healthy. Avoid smoking. About 3–5% of COPD patients carry MZ.
Pi*SZ
Moderately reduced (~35–40% of normal)
Moderate, especially if smoking
Low
Moderate deficiency. May develop emphysema, especially with smoking exposure.
Pi*ZZ
Severely reduced (~10–15% of normal, typically <57 mg/dL)
High
Significant (10–15% of adults develop cirrhosis)
Severe deficiency. Most common genotype requiring augmentation therapy. Both lung and liver risk.
Pi*Null/Null or Pi*Z/Null
Undetectable or very low
Very high
Low (no misfolded protein produced in Null/Null)
Rarest. Highest emphysema risk. Null alleles produce no AAT at all, so no liver polymerization in Null/Null.
Because AATD is inherited, diagnosis in one family member has implications for the entire family:
If one parent is Pi*ZZ and the other is Pi*MM, all children will be Pi*MZ carriers
If both parents are Pi*MZ carriers, each child has a 25% chance of being Pi*ZZ
All first-degree relatives of a diagnosed individual should be tested
Genetic counseling is recommended for family planning discussions
Testing children is a personal family decision; the Alpha-1 Foundation provides guidance on considerations
What is my exact SERPINA1 genotype?
What is my serum AAT level, and what does it mean for my risk?
Should my family members be tested?
Should I see a pulmonologist, a hepatologist, or both?
Do I need a baseline CT scan to assess for emphysema?
Am I a candidate for augmentation therapy?
Is genetic counseling available?
Are there clinical trials appropriate for my genotype?
Lung Disease in Alpha-1
The primary lung manifestation of AATD is emphysema — specifically, panacinar (panlobular) emphysema that often begins in the lower lobes. This differs from the centrilobular, upper-lobe-predominant emphysema typically seen in smokers without Alpha-1. Many patients also develop features of chronic bronchitis, bronchiectasis, or an asthma-like component.
In healthy lungs, AAT continuously neutralizes neutrophil elastase released during normal immune surveillance and infection responses. In AATD, without adequate AAT, neutrophil elastase progressively degrades elastin — the protein that gives lung tissue its elasticity and allows the air sacs to inflate and deflate. Over years, this leads to:
Destruction of alveolar walls (emphysema)
Loss of elastic recoil
Air trapping and hyperinflation
Progressive airflow obstruction
Breathlessness, exercise limitation, and reduced quality of life
Rate of decline: In non-smoking Pi*ZZ individuals, FEV1 declines at approximately 50–80 mL/year (compared to 25–30 mL/year in healthy non-smokers). In Pi*ZZ smokers, decline can be 100–150 mL/year or more. Even modest reductions in the rate of decline can translate to years of preserved lung function.
Progressive shortness of breath, especially with exertion
Wheezing
Chronic cough, with or without sputum production
Frequent chest infections (bronchitis, pneumonia)
Reduced exercise tolerance
Barrel-shaped chest (in advanced emphysema)
Symptoms typically begin between ages 30 and 50 in Pi*ZZ individuals, earlier in smokers
Red flag pattern: If you are diagnosed with COPD or emphysema before age 50, have never smoked, have lower-lobe-predominant emphysema on CT, or have a family history of emphysema or liver disease, Alpha-1 testing is essential.
Augmentation Therapy — The Disease-Specific Treatment
Augmentation therapy (also called replacement therapy or IV AAT therapy) is the only FDA-approved treatment that directly addresses the underlying protein deficiency in Alpha-1 lung disease. It involves weekly intravenous infusions of purified AAT protein derived from pooled human plasma.
The goal is to raise AAT levels in the blood and lungs above the “protective threshold” of 11 µmol/L (approximately 57 mg/dL), the level below which lung tissue is insufficiently protected from neutrophil elastase. After each weekly infusion, AAT levels rise above this threshold and are maintained above it for most of the week.
What augmentation therapy does:
Raises blood AAT levels above the protective threshold
Slows the rate of emphysema progression (as measured by CT lung density)
May reduce the frequency or severity of lung infections (some observational data)
What augmentation therapy does NOT do:
It does NOT reverse existing lung damage or emphysema
It does NOT treat liver disease — augmentation infuses normal donor (M-type) AAT and does not change the abnormal Z-AAT your own liver makes, so it neither helps nor worsens Alpha-1 liver disease
It is NOT a substitute for standard COPD medications, pulmonary rehabilitation, or smoking cessation
Product
Manufacturer
Formulation
Infusion Time
Notes
Prolastin-C
Grifols
Lyophilized powder
~15 min
Most widely used product globally
Zemaira
CSL Behring
Lyophilized powder
~15 min
Comparable efficacy to Prolastin-C
Aralast NP
Takeda (Shire)
Lyophilized powder
~15 min
Nanofiltration for enhanced viral safety
Glassia
Takeda (Kamada)
Ready-to-use liquid
~60–80 min
Only liquid formulation; no reconstitution needed. Slower infusion rate. Also approved for self-administration at home.
Dose: All products are dosed at 60 mg/kg body weight, administered intravenously once weekly.
Self-infusion at home: Many patients learn to self-infuse at home after training, improving convenience and quality of life. Home infusion nursing services are also widely available. Insurance typically covers augmentation therapy for Pi*ZZ and Pi*Z/Null individuals with evidence of airflow obstruction.
The RAPID trial (2015) is the most important randomized controlled trial for augmentation therapy. It enrolled 180 patients with Pi*ZZ AATD and FEV1 of 35–70% predicted. Key findings:
Augmentation therapy with Zemaira at 60 mg/kg/week significantly slowed the rate of lung density loss compared to placebo, as measured by CT densitometry
The annual rate of lung density decline was 1.50 g/L with augmentation vs. 2.19 g/L with placebo (difference 0.69 g/L/year in the per-protocol analysis)
No significant difference in FEV1 decline was detected, consistent with previous trials — CT densitometry is more sensitive than spirometry for detecting treatment effects in Alpha-1
The RAPID Extension trial (RAPID-OLE) showed that patients initially on placebo who switched to augmentation therapy showed a measurable slowing of lung density loss, providing additional evidence
Am I a candidate for augmentation therapy based on my genotype and lung function?
Which augmentation product do you recommend, and why?
Can I do home self-infusion, or will I need to go to an infusion center?
How will we monitor whether augmentation therapy is working?
What is my insurance coverage, and is financial assistance available?
How often should I have CT scans and pulmonary function tests?
Are there clinical trials for new treatments I should consider?
Standard COPD Management in Alpha-1
In addition to augmentation therapy, Alpha-1 patients with lung disease should receive all standard COPD treatments recommended by GOLD guidelines. These medications and strategies improve symptoms and quality of life even though they do not address the underlying AAT deficiency.
Long-acting bronchodilators (LABA + LAMA): The backbone of COPD symptom management. Combination inhalers (e.g., tiotropium + olodaterol, umeclidinium + vilanterol) improve airflow, reduce breathlessness, and decrease exacerbation frequency.
Inhaled corticosteroids (ICS): Added to LABA/LAMA for patients with frequent exacerbations, eosinophilic inflammation, or an asthma-COPD overlap component. Used more cautiously in COPD than asthma due to infection risk. Blood eosinophil counts help guide ICS use.
Roflumilast (Daliresp): A PDE4 inhibitor that can reduce exacerbation frequency in patients with severe COPD and chronic bronchitis features.
Azithromycin (low-dose, chronic): 250 mg daily or 3 times weekly may reduce exacerbation frequency in select patients. Monitor for hearing changes and QTc prolongation.
Short-acting rescue bronchodilators: Albuterol (salbutamol) inhaler for acute symptom relief.
Pulmonary rehabilitation is one of the most effective interventions for improving quality of life in COPD, including Alpha-1-related COPD. It combines:
Supervised exercise training (aerobic and resistance)
Breathing techniques and energy conservation strategies
Nutritional counseling
Education about disease self-management
Psychological support
Studies consistently show improvement in exercise capacity, breathlessness, and quality of life. The benefits are maintained with ongoing exercise. Ask your pulmonologist for a referral.
Annual influenza vaccination
Pneumococcal vaccines: PCV20 (Prevnar 20) or PCV15 followed by PPSV23 per CDC schedule
COVID-19 vaccination and boosters per current recommendations
Tdap and Zoster (Shingrix) per age-appropriate schedules
RSV vaccine: For adults 60+ per CDC recommendations
Respiratory infections are a major cause of exacerbations and accelerated lung function decline in Alpha-1. Vaccination is a simple, high-value intervention.
For patients with end-stage Alpha-1 lung disease, lung transplantation is an option. AATD is one of the most common indications for lung transplant worldwide, accounting for about 5–10% of lung transplants.
Both single and bilateral lung transplants are performed; bilateral is increasingly preferred for better long-term outcomes
Median survival after lung transplant is approximately 5–6 years overall, with some patients living 10+ years
Referral for transplant evaluation should occur when FEV1 falls below 25–30% predicted, or when quality of life is severely impaired despite maximal medical therapy
Age cutoff varies by center but is typically 65–70 years
After lung transplant, augmentation therapy is generally discontinued because the transplanted lungs produce normal AAT levels (or the lungs are now protected by the donor’s normal tissue)
Am I on the right combination of COPD medications?
Should I be referred for pulmonary rehabilitation?
Am I up to date on all recommended vaccinations?
How often should I have pulmonary function tests and CT scans?
At what point should we discuss lung transplant evaluation?
What should I do if I develop a respiratory infection or exacerbation?
Are there any environmental or occupational exposures I should avoid?
Should I have a written action plan for exacerbations?
Are there clinical trials for new treatments available to me?
Supportive & Lifestyle Care
If you have Alpha-1 and you smoke, quitting is the single most impactful thing you can do for your health.
Smoking accelerates lung function decline by 2–3 fold in Alpha-1 patients
Pi*ZZ smokers may develop severe emphysema in their 30s or 40s, decades before non-smoking ZZ individuals
Smoking cessation slows (but does not stop) the rate of lung function decline
Evidence-based cessation aids include nicotine replacement therapy (patches, gum, lozenges), varenicline (Chantix), bupropion, and behavioral counseling
The national Quitline: 1-800-QUIT-NOW (1-800-784-8669)
Secondhand smoke: Avoid all exposure
Air pollution: Monitor air quality indices; avoid outdoor exertion on high-pollution days
Occupational dusts and fumes: Avoid jobs with significant exposure to dust, chemicals, or fumes (agriculture, mining, construction, manufacturing). If unavoidable, use appropriate respiratory protection
Wood smoke and biomass fuel: Avoid wood-burning stoves and fireplaces; ensure adequate ventilation if cooking with gas
Cannabis smoke: Inhaled cannabis smoke causes the same type of lung damage as tobacco smoke
Regular exercise improves cardiovascular fitness, muscle strength, and well-being. Walking, cycling, and swimming are excellent options. Start slowly and increase gradually.
Maintain a healthy body weight: Both underweight and obesity worsen outcomes in COPD. Underweight is associated with poor muscle mass and increased mortality; obesity increases work of breathing.
Nutrition: Adequate protein intake supports respiratory muscle function. Some patients benefit from consultation with a dietitian experienced in pulmonary disease.
Supplemental oxygen: If prescribed for exercise or continuous use, use it as directed. It improves exercise tolerance and survival in patients with chronic hypoxemia.
Because Alpha-1 (particularly the ZZ genotype) carries a risk of liver disease, alcohol consumption should be discussed with your doctor:
There is no universally agreed safe level of alcohol for Pi*ZZ individuals
Many hepatologists recommend minimal or no alcohol consumption for ZZ individuals
If liver enzyme elevations or liver disease is present, alcohol should be avoided entirely
Acetaminophen (Tylenol) should be used with caution and only at recommended doses, as it is processed by the liver
Liver Disease in Alpha-1
Liver disease in Alpha-1 is caused by a mechanism distinct from the lung disease. In the Z mutation, the AAT protein misfolds and polymerizes within liver cells (hepatocytes), forming insoluble aggregates that cannot be secreted into the bloodstream. These polymer inclusions trigger chronic inflammation, hepatocyte injury, fibrosis, and can eventually lead to cirrhosis.
Newborns: About 10% of Pi*ZZ newborns develop prolonged neonatal jaundice or neonatal hepatitis. Of these, most resolve spontaneously, but a small percentage develop progressive liver disease requiring transplant in childhood.
Adults: About 10–15% of Pi*ZZ adults develop clinically significant liver disease (fibrosis or cirrhosis), with risk increasing after age 50. Liver disease can occur independently of lung disease.
Pi*SZ individuals: Have a lower but still elevated risk of liver disease compared to Pi*ZZ.
Pi*Null/Null: Do NOT develop liver disease, because no AAT protein is produced and therefore no polymer accumulation occurs.
It is not yet possible to predict which Pi*ZZ individuals will develop significant liver disease. Genetic modifiers, environmental factors, and possibly the gut microbiome are being studied.
Liver function tests (LFTs): AST, ALT, alkaline phosphatase, bilirubin, and albumin should be checked at least annually for all Pi*ZZ individuals, and more frequently if abnormalities are detected
Liver ultrasound: Periodic abdominal ultrasound to screen for structural changes, portal hypertension, and hepatocellular carcinoma (HCC)
FibroScan (transient elastography): A non-invasive test that measures liver stiffness as a marker of fibrosis. Increasingly used to monitor Alpha-1 liver disease without repeated biopsies
Liver biopsy: May be needed to confirm diagnosis, stage fibrosis, or evaluate unexplained liver enzyme elevations. PAS-diastase staining can identify characteristic AAT polymer inclusions (globules) in hepatocytes
HCC screening: Pi*ZZ patients with cirrhosis should be screened for hepatocellular carcinoma with ultrasound every 6 months, per AASLD guidelines
Liver transplantation is curative for Alpha-1 liver disease. After transplant, the new liver produces normal AAT protein (assuming the donor was Pi*MM), and AAT levels normalize. This also corrects the underlying deficiency that causes lung disease.
AATD accounts for about 1–2% of adult liver transplants in the US
5-year survival after liver transplant for AATD is approximately 80%, comparable to other indications
Combined lung-liver transplant has been performed in rare cases where both organs have end-stage disease
Referral to a hepatologist should occur when signs of advanced liver disease develop (persistent enzyme elevations, fibrosis, portal hypertension, ascites)
Important: Augmentation therapy treats lung disease, not liver disease. It infuses normal donor (M-type) AAT into the bloodstream; it does not change the abnormal Z-AAT that your own liver produces, so it does not reduce — or worsen — the AAT polymer accumulation that drives Alpha-1 liver disease. Liver-specific therapies like fazirsiran (RNAi), which lower the liver’s production of Z-AAT, are being developed to address the liver disease mechanism directly.
Pregnancy, Fertility & Family Planning
Alpha-1 antitrypsin deficiency is inherited in an autosomal co-dominant pattern through the SERPINA1 gene: everyone carries two copies, and you inherit one from each parent. The most common severe form is the ZZ genotype; people with one Z copy (MZ) are carriers who are usually healthy. If both partners carry a Z (or other deficiency) allele, each pregnancy has a 25% chance of a child with two deficiency alleles.
Genetic counseling and partner testing. If you have AATD or a family history, genetic counseling before pregnancy is recommended, and your partner can be tested for SERPINA1 deficiency alleles to clarify the risk to children. Prenatal testing and, for some families, preimplantation genetic testing (PGT) with IVF are options to discuss. Cascade testing of close relatives is also recommended.
Pregnancy is usually well tolerated in women with AATD, and the most important factor for a healthy pregnancy is preserved lung function. Not smoking — and avoiding all secondhand smoke — is the single most important thing you can do, because smoking dramatically accelerates Alpha-1 lung damage.
Augmentation therapy in pregnancy. There is only limited data on IV augmentation therapy during pregnancy. The decision to continue or pause it is individualized with your Alpha-1 specialist based on your lung disease; pregnancy registries help inform this. Do not start or stop it on your own.
Diagnosis during pregnancy. AAT is an “acute-phase” protein, so blood levels can rise in pregnancy and may look falsely reassuring — genetic (genotype) testing, not the level alone, should be used to confirm or exclude AATD.
Liver and the newborn. Women with Alpha-1 liver disease should be co-managed by hepatology. A baby who inherits two deficiency alleles (e.g., ZZ) can occasionally develop newborn jaundice/cholestasis and should have pediatric follow-up; breastfeeding is generally encouraged. A maternal-fetal medicine (high-risk obstetrics) specialist should co-manage if you have significant lung or liver disease.
Questions to ask your doctor:
Should my partner be tested, and would genetic counseling help us understand the risk to our children?
If I become pregnant, will I continue augmentation therapy, and how will my breathing be monitored?
What lung-function tests should I have before and during pregnancy?
If our baby inherits Alpha-1, what newborn liver checks are needed?
Emerging Therapies
The Alpha-1 treatment pipeline has expanded significantly in recent years. Several approaches aim to address limitations of current augmentation therapy or target the liver disease mechanism for the first time.
INVESTIGATIONAL — Phase 3 (REDWOOD)
Fazirsiran is a subcutaneous RNA interference (RNAi) therapy that silences the SERPINA1 gene in liver cells, dramatically reducing production of the misfolded Z-AAT protein. Phase 2 data showed:
Greater than 80% reduction in circulating Z-AAT protein
Significant reduction in liver Z-AAT polymer globules on biopsy
Improvements in liver fibrosis scores in some patients
Administered subcutaneously every 12 weeks
Important nuance: By reducing AAT production, fazirsiran also reduces the already-low AAT levels in the blood. This could theoretically worsen lung protection. Whether patients on fazirsiran will also need augmentation therapy to protect their lungs is being studied. SEQUOIA was the Phase 2 trial; REDWOOD is the pivotal Phase 3 study.
INVESTIGATIONAL — Phase 2/Phase 3 Planning
Alvelestat is an oral drug that directly inhibits neutrophil elastase — the enzyme that destroys lung tissue in Alpha-1. Rather than replacing the missing protector (AAT), it blocks the attacker (NE) directly.
The ASTRAEUS Phase 2 trial evaluated alvelestat in AATD patients with lung disease
Demonstrated reductions in desmosine and isodesmosine (biomarkers of elastin breakdown) in blood and urine
Oral administration (tablet) could be significantly more convenient than weekly IV infusions
Phase 3 trials are being planned; regulatory pathway discussions are ongoing
INVESTIGATIONAL — Early Phase
Gene therapy aims to deliver a functional copy of the SERPINA1 gene using adeno-associated virus (AAV) vectors, enabling the body to produce its own normal AAT protein. Several programs have been investigated:
AAV-based gene therapy has demonstrated the ability to produce measurable AAT levels in clinical trials
Achieving and sustaining therapeutic AAT levels (above 11 µmol/L) from a single dose remains a challenge
Immune responses to the AAV vector can limit durability
Muscle-directed and liver-directed approaches are both being explored
Gene editing approaches (CRISPR-based) are in preclinical development and could potentially correct the Z mutation directly
INVESTIGATIONAL
Delivering AAT directly to the lungs by inhalation could provide higher local concentrations with potentially lower total doses. Several inhaled AAT products have been tested, but none have yet achieved FDA approval. The challenge lies in formulating a stable, respirable AAT preparation that reaches the small airways effectively. The kamada InnoVAATe trial with inhaled AAT (Kamada Ltd.) did not meet its primary endpoint.
Clinical Trials — Finding and Enrolling
Because Alpha-1 is a rare disease, clinical trials are especially important. Every patient who enrolls contributes to knowledge that can improve treatment for the entire Alpha-1 community. The Alpha-1 Foundation actively tracks and promotes awareness of trials for AATD.
Search ClinicalTrials.gov for “alpha-1 antitrypsin gene therapy”
Note: Trial NCT numbers should be verified on ClinicalTrials.gov for current status and enrollment availability. Trial information changes frequently.
Alpha-1 Foundation Clinical Trials:alpha1.org/clinical-trials — Curated list of currently enrolling trials for AATD
ClinicalTrials.gov (clinicaltrials.gov): Search for “alpha-1 antitrypsin deficiency” and filter by status (recruiting), location, and condition
Alpha-1 Foundation: 1-877-228-7321 — Staff can help match you to appropriate trials
Alpha-1 Clinical Resource Centers: Academic medical centers designated by the Alpha-1 Foundation to provide expert care and trial access
Your pulmonologist or hepatologist: Ask specifically about trials at each visit
Do not assume trials are a “last resort.” Many Alpha-1 trials are for patients at all stages of disease. Participating in research helps the entire Alpha-1 community.
International Access & Regulatory Landscape
Access to augmentation therapy and other Alpha-1 treatments varies significantly by country.
Region
Augmentation Available?
Notes
United States
Yes (4 products FDA-approved)
Most widely available. Insurance coverage generally requires Pi*ZZ or Pi*Z/Null with evidence of airflow obstruction. Self-infusion at home available.
Canada
Yes (Prolastin-C approved)
Provincial coverage varies. Some provinces cover augmentation, others require individual justification.
European Union
Varies by country
Available in Germany, Spain, Italy, France, and several other countries. Not available in the UK (NICE has not recommended it due to cost-effectiveness concerns). Coverage and access vary significantly.
United Kingdom
Not recommended by NICE
NICE declined to recommend augmentation therapy based on cost-effectiveness analysis. Some patients access it through individual funding requests or clinical trials.
Japan
Limited
AATD is extremely rare in Japan. Limited awareness and access.
Australia / New Zealand
Limited availability
Access through special access schemes or clinical trials. Not PBS-listed in Australia.
Alpha-1 Foundation (US):alpha1.org — Leading US patient organization, funding research, education, and advocacy
Alpha-1 Global: International alliance of Alpha-1 patient organizations
EARCO (European Alpha-1 Research Collaboration): European registry and research network
COPD Foundation (US): Broader respiratory disease resources including Alpha-1
Failed & De-Adopted Therapies
Knowing what has been tried and did not work is important for evaluating new options and avoiding treatments that have already been studied and found ineffective.
FAILED PRIMARY ENDPOINT The InnoVAATe trial evaluated inhaled AAT (Kamada Ltd.) in patients with AATD and emphysema. The trial did not meet its primary endpoint of slowing FEV1 decline compared to placebo. Challenges included variability in drug delivery to the small airways and the difficulty of demonstrating FEV1 benefit over the trial duration. Further development of inhaled AAT has been uncertain.
DISCONTINUED Several attempts to produce recombinant (non-plasma-derived) AAT have been made, including production in transgenic animals and yeast. None have achieved FDA approval due to challenges with the protein’s glycosylation pattern, short half-life, and manufacturing scalability. Plasma-derived products remain the standard.
FAILED Danazol was studied as a potential way to increase endogenous AAT production. While it raised AAT levels modestly in Pi*MZ carriers, it did not raise levels sufficiently in Pi*ZZ individuals to reach the protective threshold. Significant side effects (liver toxicity, hormonal effects) made it unsuitable for long-term use.
FAILED 4-Phenylbutyrate (4-PBA) was investigated as a chemical chaperone that could help misfolded Z-AAT protein fold correctly and be secreted from liver cells. While it showed modest effects in cell culture and animal models, clinical studies did not demonstrate meaningful increases in serum AAT levels in Pi*ZZ humans.
Why this matters: If someone suggests one of these therapies, you now know its history. Always ask your doctor: “Has this been tested in a clinical trial for Alpha-1, and what were the results?”
Should I have liver function tests and imaging, and how often?
Do I need a FibroScan or liver biopsy?
At what point should I see a hepatologist?
Am I a candidate for any of the new therapies in clinical trials?
If I go on fazirsiran or another liver-targeted therapy, will I still need augmentation?
Should I avoid alcohol entirely?
How should I be screened for liver cancer?
Would combined lung-liver management be appropriate for me?
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Specialty Centers
Alpha-1 is best managed by physicians with experience in this specific genetic condition. The Alpha-1 Foundation has designated Clinical Resource Centers (CRCs) at academic medical centers across the country that provide expert multidisciplinary care.
No endorsement. Listing a center here does not constitute an endorsement or recommendation. Trouvera has no financial relationship with any medical center listed unless explicitly disclosed. Patients should evaluate centers based on their own needs and in consultation with their medical team.
Huntsman Cancer Institute / University of Utah Pulmonary Division
Academic medical center with pulmonary and hepatology expertise
Location: Salt Lake City, UT Phone: 801-581-2121 Programs: University of Utah Pulmonary Division provides comprehensive COPD and Alpha-1 care. Hepatology services available through University of Utah Health. ARUP Laboratories provides SERPINA1 genotyping and AAT level testing as a national reference laboratory.
Intermountain Health Pulmonology
Location: Salt Lake City, UT (multiple locations) Phone: 801-442-2000 Programs: Pulmonology services across the Intermountain Health system. COPD management and augmentation therapy coordination.
Primary Children’s Hospital
Location: 100 N Mario Capecchi Dr, Salt Lake City, UT 84113 Phone: 801-662-1000 Programs: Pediatric pulmonology and hepatology for children diagnosed with Alpha-1.
How to choose.University of Utah = academic medical center with pulmonary and hepatology divisions, ARUP diagnostics, and research capabilities. Intermountain Health = broad geographic coverage with multiple locations, often in-network, community-based pulmonary care.
Information verified May 2026. Availability changes — confirm with each institution directly.
National Jewish Health
Location: Denver, CO · Phone: 877-225-5654
Alpha-1 Foundation Clinical Resource Center. One of the nation’s leading respiratory hospitals. Comprehensive Alpha-1 program with augmentation therapy management, pulmonary rehabilitation, and clinical trial access.
Medical University of South Carolina (MUSC)
Location: Charleston, SC · Phone: 843-792-1414
Alpha-1 Foundation Clinical Resource Center. Leading Alpha-1 research and clinical program. Strong liver disease expertise.
University of Florida
Location: Gainesville, FL · Phone: 352-265-0111
Alpha-1 Foundation Clinical Resource Center. Home to Alpha-1 Foundation research initiatives. Pulmonary and hepatology expertise.
Cleveland Clinic
Location: Cleveland, OH · Phone: 800-223-2273
Alpha-1 Foundation Clinical Resource Center. Comprehensive respiratory institute with lung transplant capabilities.
Oregon Health & Science University (OHSU)
Location: Portland, OR · Phone: 503-494-8311
Alpha-1 Foundation Clinical Resource Center. Pulmonary and hepatology Alpha-1 expertise.
University of Cincinnati
Location: Cincinnati, OH · Phone: 513-558-1000
Alpha-1 Foundation Clinical Resource Center. Research programs in AATD genomics and treatment.
Mayo Clinic Rochester
Location: Rochester, MN · Phone: 507-538-3270
Pulmonary and hepatology services. Lung and liver transplant programs. Clinical trials.
VA Alpha-1 Care
The VA system provides pulmonary care including augmentation therapy through its medical centers. Veterans with Alpha-1 should ask about:
Referral to a VA pulmonologist experienced with Alpha-1
Augmentation therapy availability through VA pharmacy
Community care authorization for Alpha-1 Clinical Resource Centers if specialized care is not available within the VA system
Clinical trial access through VA-academic partnerships
George E. Wahlen VA Medical Center (Salt Lake City): 801-582-1565 VA Community Care: 1-877-881-7618
University Health Network / Toronto General Hospital
Location: Toronto, ON Phone: 416-340-4800 Programs: Lung transplant program (one of the world’s largest). Alpha-1 pulmonary expertise.
St. Paul’s Hospital / University of British Columbia
Location: Vancouver, BC Phone: 604-682-2344 Programs: Respiratory medicine with Alpha-1 expertise. Research collaborations with Alpha-1 Canada.
Royal Free Hospital, London, UK: Hepatology center for Alpha-1 liver disease. University College London Alpha-1 program.
Beaumont Hospital, Dublin, Ireland: Alpha-1 Foundation Ireland, Irish Alpha-1 Registry.
Karolinska Institute, Stockholm, Sweden: Scandinavian Alpha-1 research.
Caregiver Guidance
Alpha-1 is a chronic, lifelong condition that affects not just the patient but the entire family. Because it is genetic, the diagnosis often impacts multiple family members simultaneously.
Help manage augmentation therapy logistics. Weekly infusions — whether at an infusion center or at home — require consistent scheduling, supply management, and monitoring. Caregivers can help coordinate with the specialty pharmacy and home infusion company.
Support smoking cessation. If the patient smokes, this is the most important lifestyle change. Be supportive but not judgmental. Offer to participate in cessation programs together.
Reduce environmental triggers. Help maintain a smoke-free home, avoid wood-burning, ensure adequate ventilation, and monitor air quality on high-pollution days.
Encourage exercise and activity. Help maintain physical activity levels. Walk together. Support attendance at pulmonary rehabilitation.
Encourage family testing. When one person is diagnosed with Alpha-1, siblings and children should be tested. This can be emotionally complex — be prepared for family members who may resist testing or feel anxious about results.
Consider genetic counseling. A certified genetic counselor can help families understand inheritance patterns, testing options, and implications for family planning.
Normalize the conversation. Alpha-1 is nobody’s fault. It is a genetic condition, not a lifestyle disease (though lifestyle factors like smoking dramatically affect outcomes).
Connect with the Alpha-1 community. The Alpha-1 Foundation hosts support groups, educational events, and an annual conference. The Big Fat Reference Guide (BFRG) is a comprehensive patient resource.
Alpha-1 Foundation support line: 1-877-228-7321
Online communities: Alpha-1 Foundation online community, AlphaNet peer support, and various social media groups connect patients and families across the country.
Caregiver self-care. Chronic disease caregiving is demanding. Seek your own support networks, maintain your health appointments, and accept help when offered.
Glossary
AAT
Alpha-1 antitrypsin. A protease inhibitor protein produced by the liver that protects the lungs from neutrophil elastase damage.
AATD
Alpha-1 antitrypsin deficiency. A genetic condition causing low levels of AAT protein.
Augmentation therapy
Weekly IV infusions of purified human AAT protein to raise blood levels above the protective threshold. Also called replacement therapy.
Autosomal co-dominant
Inheritance pattern where both copies of a gene contribute to the trait. In AATD, both alleles affect AAT levels.
Bronchiectasis
Permanent widening of the airways that can cause chronic cough and frequent infections. Can occur in Alpha-1.
CT densitometry
A method of measuring lung tissue density on CT scans. More sensitive than spirometry for detecting early emphysema progression.
Emphysema
Destruction of the tiny air sacs (alveoli) in the lungs, causing shortness of breath and reduced gas exchange. The primary lung manifestation of AATD.
FEV1
Forced expiratory volume in 1 second. The amount of air you can blow out in one second. The standard measure of airflow obstruction in COPD.
FibroScan
Transient elastography. A non-invasive test that measures liver stiffness as a proxy for fibrosis.
GOLD
Global Initiative for Chronic Obstructive Lung Disease. Publishes international COPD management guidelines.
Neutrophil elastase
An enzyme released by white blood cells that breaks down elastin in lung tissue. Normally neutralized by AAT.
Panacinar emphysema
Emphysema affecting the entire air sac unit, typically starting in the lower lobes. Characteristic of Alpha-1 (vs. centrilobular emphysema in smokers).
Pi (Protease inhibitor) typing
The nomenclature system for SERPINA1 alleles. M = normal, Z = most common severe deficiency allele, S = moderate deficiency allele.
Polymer
Chains of misfolded Z-AAT protein that accumulate inside liver cells, causing liver disease.
Protective threshold
The minimum AAT blood level (11 µmol/L or ~57 mg/dL) believed necessary to adequately protect lung tissue from neutrophil elastase.
RNAi (RNA interference)
A technology that silences specific genes. Fazirsiran uses RNAi to reduce production of mutant Z-AAT protein in the liver.
SERPINA1
The gene that provides instructions for making AAT protein. Mutations in this gene cause AATD.
Sources and Further Reading
This guide draws on published medical literature, clinical trial records, and the work of physicians and researchers specializing in Alpha-1 Antitrypsin Deficiency. Key sources are listed below.
Primary Resources
Alpha-1 Foundation (alpha1.org) — Patient education, free testing (ACT Study), research funding, Clinical Resource Centers, support services (1-877-228-7321)
AlphaNet (alphanet.org) — Disease management and coordination for Alpha-1 patients on augmentation therapy
ClinicalTrials.gov (clinicaltrials.gov) — Search “alpha-1 antitrypsin deficiency” for current trials
COPD Foundation (copdfoundation.org) — Resources for all COPD patients including Alpha-1
National Heart, Lung, and Blood Institute (NHLBI) (nhlbi.nih.gov) — Alpha-1 information from the NIH
Key Guideline and Trial References
ATS/ERS Statement: American Thoracic Society / European Respiratory Society Statement: Standards for the Diagnosis and Management of Individuals with Alpha-1 Antitrypsin Deficiency. Am J Respir Crit Care Med. 2003;168(7):818–900.
RAPID Trial: Chapman KR, Burdon JGW, Piitulainen E, et al. Intravenous augmentation treatment and lung density in severe alpha-1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;386(9991):360–368. (NCT00261833)
RAPID-OLE: McElvaney NG, Burdon J, Holmes M, et al. Long-term efficacy and safety of alpha-1 proteinase inhibitor treatment for emphysema caused by severe alpha-1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE). Lancet Respir Med. 2017;5(1):51–60.
GOLD 2026: Global Initiative for Chronic Obstructive Lung Disease (GOLD) Report 2026. goldcopd.org
Alpha-1 Foundation Clinical Resource Center Guidelines
Strnad P, et al.: Alpha-1-Antitrypsin Deficiency. N Engl J Med. 2020;382(15):1443–1455. (Comprehensive review)
AASLD Practice Guidance: Evaluation of the patient for liver disease in alpha-1 antitrypsin deficiency. aasld.org
External links notice: Links to government agencies, academic institutions, and private organizations are provided for informational convenience. Linking does not constitute endorsement by Trouvera, and we cannot attest to the accuracy of external content. You will be subject to the destination site’s privacy policy when you leave this site.
A practical test for any online claim: If a website is making a claim about Alpha-1 treatment that does not appear anywhere in PubMed, the Alpha-1 Foundation, or ATS/ERS guidelines, that should be a significant warning sign.
What This Guide Does Not Know
An honest guide names its own limits:
This guide cannot diagnose, treat, or predict outcomes for any individual. It does not know your genotype, AAT level, lung function, liver status, or personal circumstances. Only your medical team can create your specific care plan.
Alpha-1 research is evolving. New trial results, drug approvals, and guideline updates occur over time. Every time-sensitive fact should be re-verified with your medical team, on ClinicalTrials.gov, and through the Alpha-1 Foundation.
Drug availability varies by country. This guide focuses primarily on FDA-approved therapies. Access to augmentation therapy and emerging treatments differs significantly in Europe, Canada, Asia, and other regions.
Individual outcomes vary widely. Some Pi*ZZ individuals develop severe lung and liver disease; others remain relatively healthy into old age. The reasons for this variability are not fully understood.
This is a rare disease. Not all pulmonologists or hepatologists have extensive experience with Alpha-1. Connecting with an Alpha-1 Foundation Clinical Resource Center or experienced specialist is often the single highest-value step a patient can take.
A final word. Alpha-1 can feel isolating because most people — including many doctors — have never heard of it. But you are not alone. The Alpha-1 community is strong, well-organized, and growing. Augmentation therapy slows lung disease. Liver disease can be monitored and managed. A new generation of therapies is in clinical trials. Get tested, get connected, and get treated. The Alpha-1 Foundation is an extraordinary resource — start there. Help is real. Use it.
Important Safety Information
Alpha-1 antitrypsin deficiency (A1AD) treatment involves augmentation therapy (IV infusions of purified AAT protein) and, for some patients, liver or lung transplantation. Key safety considerations are outlined below.
IgA deficiency risk: AAT augmentation products are derived from pooled human plasma and contain trace amounts of IgA. Patients with severe IgA deficiency (complete IgA absence) who have developed anti-IgA antibodies may experience severe anaphylactic reactions. Your doctor should check your IgA level before starting augmentation therapy.
Infusion reactions: Some patients experience infusion-related reactions including fever, chills, nausea, chest tightness, or blood pressure changes. These are usually mild and can be managed by slowing the infusion rate or pre-medicating. Report any severe or worsening symptoms during an infusion immediately.
Viral safety: AAT products undergo viral inactivation steps, but because they are plasma-derived, there is a theoretical (extremely low) risk of transmission of known or unknown infectious agents. All plasma-derived AAT products meet rigorous safety standards.
No benefit in liver disease: Augmentation therapy only addresses the lung manifestations of A1AD by increasing AAT levels in the lungs. It does not treat the liver accumulation of misfolded Z-AAT protein and should not be expected to improve liver disease.
Critical warning: Smoking and lung protection:
Smoking is the single greatest modifiable risk factor in A1AD. In patients with severe AAT deficiency (ZZ genotype), smoking accelerates lung destruction dramatically — decades faster than in non-smokers. Even secondhand smoke exposure causes ongoing harm to the lungs.
Smoking cessation counseling and pharmacotherapy (varenicline/Chantix, bupropion, or NRT) are strongly recommended and should be considered part of A1AD treatment. Most insurance covers smoking cessation treatment. Utah Quitline: 1-800-QUIT-NOW (1-800-784-8669).
Cannabis and respiratory irritants: Inhaled cannabis and e-cigarette aerosols can also damage airways; their impact on A1AD-related lung disease is not well studied but avoidance is prudent.
For patients with A1AD liver disease:
Alcohol use accelerates liver fibrosis and cirrhosis in A1AD with significant liver involvement. Patients with A1AD liver disease should avoid alcohol entirely.
Acetaminophen (Tylenol) should be used cautiously and at the lowest effective dose in patients with significant liver disease; avoid in acute liver failure. NSAIDs (ibuprofen, naproxen) also carry increased GI and renal risks.
If you are being evaluated for liver transplantation, the transplanted liver will produce normal AAT, effectively correcting the metabolic defect. Discuss vaccination status (hepatitis A, hepatitis B) with your liver team — these are important before liver disease progresses.