PMID- 32697896 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210212 IS - 2372-952X (Print) IS - 2372-952X (Electronic) IS - 2372-952X (Linking) VI - 7 IP - 3 DP - 2020 Jul TI - Non-Invasive Assessment and Management of Liver Involvement in Adults With Alpha-1 Antitrypsin Deficiency. PG - 260-271 LID - 10.15326/jcopdf.7.3.2019.0161 [doi] AB - Alpha-1 antitrypsin deficiency (AATD) is a systemic disorder affecting mainly the lung and the liver and is caused by mutations in SERPINA1, the AAT gene. A homozygous "Pi*Z" mutation (Pi*ZZ genotype) may cause liver fibrosis on its own independently of pulmonary AATD manifestation, while heterozygous Pi*Z carriage (Pi*MZ genotype) is considered a strong risk factor for development of liver cirrhosis in patients with concomitant liver disease such as alcoholic and non-alcoholic liver disease. In Pi*ZZ homozygotes, liver disease constitutes the second leading cause of death and is highly heterogeneous. About 35% of Pi*ZZ individuals display significant liver fibrosis on biopsy (i.e., fibrosis stage >/= 2 on scale 0-4). Among non-invasive methods for liver fibrosis assessment, liver stiffness measurement (LSM) via vibration-controlled transient elastography (VCTE) has been most widely evaluated. Based on these data, Pi*ZZ adults have 20x increased odds of developing advanced liver fibrosis (i.e., fibrosis stage >/= 3) than adults without AAT mutation. Risk factors for accelerated fibrosis progression are male sex, age >/= 50 years, alcohol misuse, obesity, diabetes mellitus, or metabolic syndrome. Unlike VCTE, other ultrasound- and magnetic resonance-based elastography methods have been assessed in small cohorts of Pi*ZZ individuals and remain to be comprehensively validated. Among blood-based fibrosis tests, AST-to-platelet ratio index (APRI) correlates moderately with histologic fibrosis stage and LSM. Given APRI's wide availability, it can be used for risk stratification as an adjunct to LSM or when LSM is not at hand. Despite recent efforts, AATD-related liver disease, especially for genotypes other than Pi*ZZ, remains greatly understudied. AATD individuals should be offered liver biochemistry, liver ultrasound, and non-invasive fibrosis assessment at the time of diagnosis to detect potential complications and for proper risk stratification. If signs of AATD-related liver disease occur (i.e., pathologic fibrosis test or repeatedly elevated liver enzymes), patients should be referred to a health care center specialized in AATD-related liver disease and be screened for potentially treatable comorbidities. To exclude the latter, they may need a liver biopsy. Moreover, every health care provider of an AATD individual should be aware of the potential liver manifestation, counsel their patient on modifiable hepatic risk factors, and offer them regular liver check-ups. CI - JCOPDF (c) 2020. FAU - Hamesch, Karim AU - Hamesch K AD - Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany. AD - Coordinating Center for Alpha-1 Antitrypsin Deficiency-Related Liver Disease of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER) and the European Association for the Study of the Liver (EASL) Registry Group "Alpha-1 Liver". FAU - Strnad, Pavel AU - Strnad P AD - Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany. AD - Coordinating Center for Alpha-1 Antitrypsin Deficiency-Related Liver Disease of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER) and the European Association for the Study of the Liver (EASL) Registry Group "Alpha-1 Liver". LA - eng GR - SFB/TRR57/Deutsche Forschungsgemeinschaft (DFG) consortium/Germany GR - Interdisciplinary Center for Clinical Research (IZKF)/Germany GR - Else Kroener Excellence Fellowship/Germany GR - START program/Germany GR - German Liver Foundation/Germany GR - German Gastroenterological Association/Germany PT - Journal Article PT - Review PL - United States TA - Chronic Obstr Pulm Dis JT - Chronic obstructive pulmonary diseases (Miami, Fla.) JID - 101635411 PMC - PMC7857717 OTO - NOTNLM OT - AATD OT - SERPINA1 OT - alpha-1 antitrypsin deficiency OT - elastography OT - genetic liver disease OT - liver fibrosis OT - liver stiffness OT - rare liver disease COIS- PS has received speaker or consulting fees from Grifols, CSL Behring, Alnylam, and Arrowhead Pharmaceuticals. KH has received speaker fees from CSL Behring. EDAT- 2020/07/23 06:00 MHDA- 2020/07/23 06:01 PMCR- 2020/06/29 CRDT- 2020/07/23 06:00 PHST- 2020/07/23 06:00 [pubmed] PHST- 2020/07/23 06:01 [medline] PHST- 2020/07/23 06:00 [entrez] PHST- 2020/06/29 00:00 [pmc-release] AID - 10.15326/jcopdf.7.3.2019.0161 [doi] PST - ppublish SO - Chronic Obstr Pulm Dis. 2020 Jul;7(3):260-271. doi: 10.15326/jcopdf.7.3.2019.0161.