Alpha-1: A story of underdiagnosed genetic liver disease
Unraveling Alpha-1: A sibling story of an underdiagnosed genetic disease
This article includes real-life patient experiences. Individual experiences may vary. This information is available to the general public for informational purposes only; it should not be used for diagnosing or treating a health condition or disease. It is not intended to substitute for consultation with a health care professional. Please consult your health care provider for further advice.
Lorrinda and Bill are paid consultants for Takeda.
Only one year apart in age, Lorrinda and her brother Bill have always had a close relationship.
“Even if I haven’t seen her in a while,” says Bill, “if I need her, she’s there for me, no matter what.”
Lorrinda explains that’s because “I always saw myself as my little brother’s protector.”
So when she found out Bill had end-stage liver disease, she was heartbroken.
“The hardest part for me was watching him go through it, and to know everything that was getting ready to happen.” For example, he would need a liver transplant*. Lorrinda received hers in 2018. That’s when she learned she had been living with alpha-1 antitrypsin deficiency (AATD) liver disease (also known as Alpha-1 liver disease). While not all patients have the same journey, she and Bill would eventually discover he also had the underdiagnosed genetic condition.
Due to low awareness of AATD liver disease among doctors and patients,1 and because the disease often progresses without symptoms, people can live unknowingly with the condition until their liver has failed, or diagnostic testing is done.1,2
That’s what happened to Lorrinda. “Looking back, I was sick for more than a decade before I was told I had Alpha-1 liver disease.”
Journey to an accurate diagnosis
Lorrinda says people with high liver enzymes should be screened for AATD because not everyone knows or talks about their family history.
“When the doctor came in after my transplant and told me the news, I was shocked because I didn’t even know what Alpha-1 liver disease was. Over the years, I had multiple blood tests showing consistently high liver enzymes. But no one had brought up Alpha-1 before,” she says.
Bill was also diagnosed with fatty liver disease in his 30s, but he never made the connection to AATD liver disease. He had very different symptoms and says, “I didn’t put two and two together with Lorrinda.” His doctors didn’t either. About two years ago, his condition began to deteriorate rapidly.
Bill’s symptoms differed from his sister’s, but they both had high liver enzymes.
“My wife kept telling me I didn’t look good and that I was acting different. People told me I sounded drunk because my speech was slurred. My legs were swelling, and I would get really tired and out of breath going up the stairs in my house,” he says.
Doctors sent Bill to an oncologist to have bone marrow extracted. The good news—it wasn’t cancer. The bad news—blood tests showed Bill had cirrhosis and needed a liver transplant to survive. After his transplant, testing revealed he had AATD liver disease, just like his sister.
Lorrinda shares how many pills she takes each day to maintain liver heath and address other health issues, some resulting from her transplant.
Barriers to diagnosis
Takeda’s global program leader for gastrointestinal and inflammation says it’s important to recognize the spectrum of the condition.
“There’s a misconception that Alpha-1 only impacts the lungs, and there’s a lack of awareness about the liver disease that may be present,” says Nirav Desai, M.D. “This can lead to underdiagnosis.”
Currently, there are no hepatologist consensus recommendations on AATD liver disease,4 but given the relative ease of diagnostic blood tests, he says “All patients with elevated liver enzymes should undergo testing for alpha-1 antitrypsin deficiency.”
While the AATD community works toward the creation of recommendations, Dr. Desai says Takeda is taking a multi-pronged approach to streamlining the pathway to a more timely and accurate patient diagnosis.
“We’re engaging academic societies, health care professionals and patient advocacy groups in multiple countries to build greater awareness of unmet needs in AATD. And we’re working to deepen understanding of genotypes and prevalence, biomarkers, natural history and disease progression through ongoing evidence generation.”
Benefits of early detection
Early detection of AATD liver disease can allow for timely lifestyle interventions (such as diet) that can help potentially slow liver damage, as well as enable people to screen at-risk family members who may be carriers of the genetic disorder.5,6,7
Lorrinda and Bill discuss family health history with Bill’s daughter Presley, who has also tested positive for AATD.
Knowing what they know now, Lorrinda says she and Bill look at their family history differently.
“Our mom and uncle passed away from lung disease before I was diagnosed. If I had been diagnosed sooner with Alpha-1, could that information have helped them? Could it have helped Bill?” she wonders.
These siblings are sharing their stories in hopes of raising awareness and helping other families avoid delayed diagnosis.
“I believe doctors do great things, but I know not all doctors know the same thing at the same time,” Lorrinda says. “We’re using our voices,” to help more doctors help more patients, she says.
* Liver transplant is currently the only treatment for patients with AATD who have end-stage liver disease. An estimated 2.4% of those diagnosed with AATD have a history of liver transplantation. ** The symptoms of AATD liver disease and end-stage liver disease can vary and Lorrinda’s and Bill’s experiences may not be representative of your own experience. Always consult a health care professional for medical advice or service.
| The science behind AATD |
|---|
| Alpha-1 antitrypsin (AAT) is a protein produced in liver cells that protects lung tissue from damage caused by certain enzymes.8 In AATD, a mutation in the SERPINA1 gene can lead to liver disease independently or in combination with lung disease.9 People with the Pi*ZZ genotype have the highest likelihood of liver injury. Genetic testing can identify this genotype.10 In AATD liver disease, mutated AAT accumulates in the liver cells, which can cause chronic liver damage over time, including fibrosis, cirrhosis and potentially hepatocellular carcinoma.11 |
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- Narayanan P, Mistry PK. Update on alpha‐1 antitrypsin deficiency in liver disease. Clin Liver Dis (Hoboken). 2020;15(6):228-235.
- Tejwani V, Wang XF, Stoller JK. The natural history of lung function in severe deficiency of alpha-1 antitrypsin following orthotopic liver transplantation: a case report. Chronic Obstr Pulm Dis. 2015;2(4):290-295.
- Hamesch K, Strnad P. Non-invasive assessment and management of liver involvement in adults with alpha-1 antitrypsin deficiency. Chronic Obstr Pulm Dis. 2020;7(3):260-271.
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- Brantly M, Campos M, Davis AM, et al. Detection of alpha-1 antitrypsin deficiency: the past, present and future. Orphanet J Rare Dis. 2020:15(1):96.
- Healthy eating, healthy liver: the links between nutrition and liver wellness. Global Liver Institute. Accessed March 21, 2025. https://globalliver.org/healthy-eating-healthy-liver-the-links-between-nutrition-and-liver-wellness/
- Strnad P, Mandorfer M, Choudhury G, et al. Fazirsiran for liver disease associated with alpha1-antitrypsin deficiency. N Engl J Med. 2022;387(6):514-524.
- Karatas E, Di-Tommaso S, Dugot-Senant N, Lachaux A, Bouchecareihl M. Overview of alpha-1 antitrypsin deficiency- mediated liver disease. EMJ Hepatol. 2019;7(1):65-79.
- American Thoracic Society; European Respiratory Society. 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.
- Mitchell EL, Khan Z. Liver disease in alpha-1 antitrypsin deficiency: current approaches and future directions. Curr Pathobiol Rep. 2017;5(3):243-252.
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