Alpha-1 antitrypsin deficiency-associated liver disease: A review focusing on new assessment tools and therapies

Alpha-1-antitrypsin deficiency (AATD) is an autosomal codominant genetic disorder, often going undiagnosed. AATD results from malformed or deficient AAT proteins, which predispose individuals to obstructive pulmonary disease and liver disease. The PI*ZZ genotype is the most common and severe, but even milder genotypes like PI*SZ and PI*MZ can lead to lung and liver disease, particularly when combined with metabolic disfunction. The rate ranges of ZZ liver-related mortality are 10 to 40 %. Despite ongoing clinical trials, there is currently no approved therapy for AATD-associated liver disease (AATD-LD), and liver transplantation remains the only curative option. AATD-LD can progress slowly for decades, with contributing factors such as metabolic dysfunction-associated steatotic liver disease, alcohol use, and hepatitis accelerating disease progression. Moreover, these factors complicate the accurate diagnosis of AATD-LD. To date, data on blood markers or non-invasive markers for monitoring and predicting the evolution of AATD-LD are few and not as numerous as for other liver diseases. Moreover, a correct staging of the patient is important not only for the follow-up of the patient but also to evaluate the inclusion of the patient in experimental protocols. This review aims to evaluate non-invasive techniques for monitoring the AATD-LD.