What Are the Treatments for Alpha-1 Liver Disease?

Currently, there are no FDA-approved medications specifically designed to cure or treat the liver disease caused by Alpha-1 Antitrypsin Deficiency (AATD) ^[1][2]. Standard medical care today focuses on protecting the liver from further damage, managing symptoms of liver disease, and monitoring for complications like cirrhosis or liver cancer ^[3]. For end-stage liver disease, a liver transplant is the standard of care and provides a definitive cure ^[1][4]. While new, targeted drugs are actively being researched in clinical trials, today’s management is about strict surveillance, supportive care, and lifestyle modifications ^[2].

Why Augmentation Therapy Doesn’t Help the Liver

The lung and liver problems in Alpha-1 happen for completely different reasons, which is why treatments must be different.

Lung damage occurs because there isn’t enough normal AAT protein in the blood to protect the lung tissue from inflammation—a process doctors call a “loss of function” ^[5][6]. Augmentation therapy works effectively for the lungs by infusing donor AAT protein into your bloodstream to replace what is missing ^[1].

However, the liver damage in Alpha-1 is caused by a “toxic gain of function” ^[7][8]. The liver makes a mutant, misfolded version of the AAT protein (most often the Z variant) that gets physically trapped inside the liver cells (hepatocytes) ^[9]. These stuck proteins clump together into polymers, causing chronic cellular stress, damage, and eventual scarring ^[7]. Adding more normal AAT to your blood through augmentation therapy does absolutely nothing to stop the mutant proteins from piling up inside the liver cells, which is why it cannot treat Alpha-1 liver disease ^[1][6][10].

Current Standard of Care for Alpha-1 Liver Disease

Because there is no pill or infusion currently approved to stop the protein from accumulating in your liver ^[1][11], medical care relies heavily on a multidisciplinary approach to protect the liver you have ^[2]:

• Preventing Additional Damage: Doctors strongly advise patients to completely avoid alcohol, as it adds unnecessary toxic stress to an already vulnerable liver ^[2]. It is also critical to maintain a healthy weight and manage metabolic conditions ^[12]. Having overlapping non-alcoholic fatty liver disease (now called metabolic dysfunction-associated steatotic liver disease, or MASLD) on top of Alpha-1 can accelerate liver damage ^[12][13].
• Avoiding Hepatotoxins: You should work closely with your care team before starting any new prescription medications, herbal supplements, or over-the-counter drugs to ensure they are safe for your liver ^[2]. Additionally, smoking has been linked to worsened liver disease progression in severe Alpha-1, so quitting smoking is essential for both your lungs and your liver ^[14].
• Vaccinations: Because your liver is already compromised, contracting a viral liver infection can be devastating. A critical part of standard care is ensuring you are fully vaccinated against Hepatitis A and Hepatitis B ^[2].
• Routine Monitoring: Your doctor should monitor your liver health regularly. This is often done using routine blood tests (checking liver enzymes like ALT, AST, and Bilirubin) and non-invasive imaging like an ultrasound or a FibroScan (VCTE), which safely measures liver stiffness to check for scarring without needing a biopsy ^[15].
• Surveillance for Complications: If liver scarring progresses to cirrhosis, you are at a significantly higher risk for liver cancer, specifically hepatocellular carcinoma (HCC) ^[16][7]. The standard of care for anyone with cirrhosis, including those with Alpha-1, is to undergo an ultrasound every 6 months to check for early signs of cancer when it is most treatable ^[16][2].

Liver Transplantation

If Alpha-1 causes severe cirrhosis and the liver begins to fail (end-stage liver disease), liver transplantation becomes the definitive standard of care ^[4][1].

A liver transplant is essentially a cure for Alpha-1 liver disease. Because the new, healthy donor liver will produce normal AAT protein, it will not experience the toxic build-up of misfolded proteins ^[4][1]. Furthermore, because the new liver releases normal AAT into your bloodstream, your systemic levels of AAT will normalize. While this normalization helps protect your lungs from future degradation, it does not reverse emphysema or lung damage that has already occurred ^[4]. Because Alpha-1 is a systemic condition that can affect both organs, your care team will carefully evaluate your lung function when determining if you are a safe candidate for transplant surgery ^[17][2].

Investigational RNA Therapies

While not available as standard prescriptions today, exciting new treatments are currently progressing through clinical trials.

A major focus of current research is on RNA interference (RNAi) therapies, such as fazirsiran ^[18][19]. These investigational drugs are designed to “silence” the faulty AAT gene in the liver, instructing it to stop producing the mutant Z-AAT protein entirely ^[20][18]. Early clinical studies have shown that these therapies can successfully and safely reduce the amount of toxic protein trapped in the liver, which may potentially halt or reverse the progression of liver damage ^[18][21][19].

If you are wondering how your lungs stay protected while an experimental drug stops your liver from making AAT, you are not alone. Because shutting down this production lowers your circulating AAT levels even further, patients taking RNAi therapies who need lung protection can concurrently receive standard augmentation therapy to keep their lungs safe ^[18][22].

If they eventually receive FDA approval, RNA therapies would become the very first targeted medications for Alpha-1 liver disease. Patients interested in participating in research should discuss clinicaltrials.gov or resources from the Alpha-1 Foundation with their hepatologist.