Overview
Are You and Your Team Ready? Evolving Opportunities to Identify At-Risk Patients and Change the Trajectory of Alpha-1 Antitrypsin Deficiency (AATD)-Associated Liver Disease
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Alpha-1 antitrypsin deficiency (AATD), a multisystem genetic disorder caused by mutations in the SERPINA1 gene, affects nearly 3 million people worldwide. AATD can manifest with overlapping symptoms common to pulmonary conditions such as chronic obstructive pulmonary disease (COPD), asthma, and bronchiectasis, as well as unexplained liver diseases, making symptom-based diagnosis alone unreliable. Although lung manifestations of AATD typically appear in adulthood and are more common, liver problems, which can arise at any age, are the second most common clinical manifestation and cause of death in patients with AATD.
Unfortunately, clinicians often misattribute AATD liver manifestations to more common conditions such as metabolic dysfunction-associated steatotic liver disease (MASLD) or alcohol-related liver disease, and lung symptoms to COPD or asthma without investigating an inherited etiology, leading to substantial underdiagnosis. Moreover, for those patients with a confirmed diagnosis, there are currently no specific treatment options available for AATD-related liver disease (AATD-LD), but emerging therapies may soon profoundly shift the AATD treatment paradigm.
To support specialists in their ability to navigate this complexity and support peer-to-peer learning, this training program, modeled on the CDC Training of Trainers approach, provides learners with the tools and resources to enhance early diagnosis, refine noninvasive monitoring, and support informed decision-making around emerging therapies with the potential to improve outcomes for individuals with AATD-LD.
This activity is intended for gastroenterologists, hepatologists, gastroenterology-focused advanced practice providers, pulmonologists, internists, and other members of the multidisciplinary care team.
Alpha-1 antitrypsin deficiency (AATD) is a multisystem genetic disorder caused by mutations in the SERPINA1 gene. Although AATD is classically associated with pulmonary emphysema, hepatic involvement is also significant due to intrahepatocytic accumulation of the Z alpha-1 antitrypsin (Z-AAT) protein, which leads to proteotoxicity, inflammation, fibrosis, and potential progression to cirrhosis or hepatocellular carcinoma (HCC). Despite the high risk of liver disease in certain individuals—often independent of pulmonary symptoms—AATD remains frequently underdiagnosed or misattributed. This diagnostic gap is exacerbated by the insensitivity of liver enzyme tests and ultrasound to detect early or progressive liver injury. In addition, current guidance for monitoring AATD–associated liver disease (AATD-LD) remains limited, particularly concerning the role of noninvasive tests (NITs). However, recent expert consensus recommendations established a pragmatic framework for using NITs in AATD-LD, endorsing vibration-controlled transient elastography (VCTE) as the preferred tool for initial assessment.
With evolving diagnostic paradigms, clinicians require education on NITs and guidance on individualized monitoring of patients according to baseline liver stiffness measurements, comorbid risk factors (eg, metabolic syndrome, alcohol use), and clinical presentation. Beyond diagnosis, therapeutic development in AATD-LD is advancing rapidly with emerging strategies targeting the hepatic accumulation of Z-AAT through gene editing, RNA interference (RNAi), and protein folding correction. Consequently, this educational program will also provide clinicians with the knowledge needed to refer patients for clinical trial enrollment and to prepare to incorporate disease-modifying therapies within clinical practice.
Upon completion of this activity, learners will be able to:
• Identify appropriate diagnostic approaches and genetic testing strategies to confirm alpha-1 antitrypsin deficiency (AATD)
• Appraise noninvasive test (NIT) results and proposed liver stiffness thresholds for staging and monitoring fibrosis in AATD
• Evaluate the mechanisms of action, efficacy data, and safety profiles of emerging therapeutic agents targeting AATD
• Identify appropriate diagnostic approaches and genetic testing strategies to confirm alpha-1 antitrypsin deficiency (AATD)
• Appraise noninvasive test (NIT) results and proposed liver stiffness thresholds for staging and monitoring fibrosis in AATD
• Evaluate the mechanisms of action, efficacy data, and safety profiles of emerging therapeutic agents targeting AATD
Provided by the Academy for Continued Healthcare Learning (ACHL).
Supported by an educational grant from Takeda Pharmaceuticals U.S.A., Inc.
Virginia Clark, MD, MS
Clinical Professor of Medicine
Division of Gastroenterology, Hepatology, and Nutrition
University of Florida
Gainesville, FL
Clinical Professor of Medicine
Division of Gastroenterology, Hepatology, and Nutrition
University of Florida
Gainesville, FL
Charlie Strange, MD
Professor of Pulmonary and Critical Care Medicine
Medical University of South Carolina
Charleston, SC
The Academy for Continued Healthcare Learning (ACHL) requires that the faculty participating in an accredited continuing education activity disclose all affiliations or other financial relationships within 24 months (1) with the manufacturers of any commercial product(s) and/or provider(s) of commercial services discussed in an educational presentation and (2) with all ineligible companies. All relevant financial relationships have been mitigated prior to this activity.
The following financial relationships have been provided:
Virginia Clark, MD, MS
Consulting Agreements: Takeda Pharmaceuticals
Research funding to institution: 89 Bio, Hamni Pharmaceutical, Novo Nordisk, Takeda Pharmaceuticals
Charlie Strange, MD
Consulting Agreements: AstraZeneca, Beam, Biomarin, CSL Behring, Morair, Roche, Sanofi
Research funding to institution:, Beam, Biomarin, CSA Medical, Grifols, Krystal, Nuvaira, Renovion, Takeda Pharmaceuticals
ACHL staff members and others involved with the planning, development, and review of the content for this activity have no relevant affiliations or financial relationships to disclose.
The content for this activity was developed independently of any ineligible company. All materials are included with permission. The opinions expressed are those of the faculty and are not to be construed as those of the publisher or grantor(s).
This educational activity was planned and produced in accordance with the ACCME Standards for Integrity and Independence in Accredited Continuing Education. Recommendations involving clinical medicine in a continuing medical education (CME/CE) activity must be based on evidence that is accepted within the profession of medicine as adequate justification for their indications and contraindications in the care of patients. All scientific research referred to, reported, or used in CME/CE in support or justification of a patient care recommendation must conform to the generally accepted standards of experimental design, data collection, and analysis.
This CME/CE activity might describe the off-label, investigational, or experimental use of medications and/or devices that may exceed their FDA-approved labeling. Physicians should consult the current manufacturers’ prescribing information for these products. ACHL requires the speaker to disclose that a product is not labeled for the use under discussion.
Discussion of scientific information on unapproved uses (SIUU), off-label, investigational, or experimental drug/device use: BEAM-302, WVE-006, KRRO-110, fazirsiran, BMN 349, and INBRX-101 are not approved for the treatment of AATD-LD.
Pharmacists should consult with their state pharmacy on pharmacist vaccination authority included within their scope of practice.
This activity will take up to 2.25 hours to complete. To receive credit, learners are required to complete the pre-assessment, view the online activity, and complete the posttest and evaluation. To receive credit, 60% must be achieved on the posttest. A certificate will be immediately available. There is no fee to participate in the activity or for the generation of the certificate.
The Academy for Continued Healthcare Learning is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
The Academy for Continued Healthcare Learning designates this enduring material for a maximum of 2.25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Physician assistants, nurse practitioners, and nurses may participate in this educational activity and earn a certificate of completion as AAPA, AANP, and ANCC accept AMA PRA Category 1 Credits™ through their reciprocity agreements.
