Ferreira AI, Guimarães C, Macedo Silva V, Xavier S, Magalhães J, Cotter J. Alpha-1 antitrypsin deficiency and Pi*Z allele as important co-factors in the development of liver fibrosis. World J Hepatol 2024; 16(8): 1099-1110 [PMID: 39221093 DOI: 10.4254/wjh.v16.i8.1099]
Corresponding Author of This Article
Ana Isabel Ferreira, MD, Medical Assistant, Department of Gastroenterology, Hospital da Senhora da Oliveira - Guimarães, Rua dos Cutileiros 114, Creixomil, Guimarães 4835-044, Portugal. ai.voferreira@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Hepatol. Aug 27, 2024; 16(8): 1099-1110 Published online Aug 27, 2024. doi: 10.4254/wjh.v16.i8.1099
Alpha-1 antitrypsin deficiency and Pi*Z allele as important co-factors in the development of liver fibrosis
Ana Isabel Ferreira, Catarina Guimarães, Vitor Macedo Silva, Sofia Xavier, Joana Magalhães, José Cotter
Ana Isabel Ferreira, Vitor Macedo Silva, Sofia Xavier, Joana Magalhães, José Cotter, Department of Gastroenterology, Hospital da Senhora da Oliveira - Guimarães, Guimarães 4835-044, Portugal
Ana Isabel Ferreira, Vitor Macedo Silva, Sofia Xavier, Joana Magalhães, José Cotter, Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga 4710-057, Portugal
Ana Isabel Ferreira, Vitor Macedo Silva, Sofia Xavier, Joana Magalhães, José Cotter, Life and Health Sciences Research Institute/3B’s, PT Government Associate Laboratory, Braga 4710-057, Portugal
Catarina Guimarães, Department of Pulmonology, Hospital Senhora da Oliveira - Guimarães, Guimarães 4835-044, Portugal
Author contributions: Ferreira AI, Guimarães C, Macedo Silva V, Xavier S, Magalhães J, and Cotter J contributed to the study conception and design; Ferreira AI performed material preparation, data collection and analysis, and wrote the first draft of the manuscript; all authors commented on previous versions of the manuscript; and all authors read and approved the final manuscript.
Institutional review board statement: The study was approval by the Institutional Review Board (Approval number 15/2022).
Informed consent statement: All patients gave informed, written consent prior to enrolling.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Data supporting this study cannot be made available due to ethical and legal restrictions.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ana Isabel Ferreira, MD, Medical Assistant, Department of Gastroenterology, Hospital da Senhora da Oliveira - Guimarães, Rua dos Cutileiros 114, Creixomil, Guimarães 4835-044, Portugal. ai.voferreira@gmail.com
Received: January 10, 2024 Revised: April 27, 2024 Accepted: May 17, 2024 Published online: August 27, 2024 Processing time: 224 Days and 10.2 Hours
Abstract
BACKGROUND
Alpha-1 antitrypsin deficiency (AATD) is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease, and Pi*Z allele is the most clinically relevant mutation.
AIM
To evaluate the impact of clinical parameters and AATD phenotypes, particularly the Pi*Z allele, in liver fibrosis.
METHODS
Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology consultation.
RESULTS
Included 69 patients, 49.3% had Pi*MZ phenotype and 10.1% Pi*ZZ. An age ≥ 55 years, age at diagnosis ≥ 41 years and AAT at diagnosis < 77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score (NFS) not excluding advanced fibrosis [area under the curve (AUC) = 0.840, P < 0.001; AUC = 0.836, P < 0.001; AUC = 0.681, P = 0.025]. An age ≥ 50 years and age at diagnosis ≥ 41 years predicted a fibrosis-4 index of moderate to advanced fibrosis (AUC = 0.831, P < 0.001; AUC = 0.795, P < 0.001). Patients with hypertension, type 2 diabetes mellitus (DM), dyslipidaemia, metabolic syndrome, and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis (P < 0.001, P = 0.002, P = 0.008, P < 0.001, P = 0.033). Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement ≥ 7.1 kPa (P = 0.040).
CONCLUSION
Risk factors for liver disease in AATD included an age ≥ 50 years, age at diagnosis ≥ 41 years, metabolic risk factors, regular alcohol consumption, at least one Pi*Z allele, and AAT value at diagnosis < 77 mg/dL. We created an algorithm for liver disease screening in AATD patients to use in primary care, selecting those to be referred to Hepatology consultation.
Core Tip: Patients with alpha-1 antitrypsin deficiency (AATD) who have more than 50 years of age and had a diagnosis after 41 years of age are at increased risk of developing liver fibrosis, as well as those who have at least one Pi*Z allele. In patients with AATD, the presence of metabolic risk factors, such as hypertension, type 2 diabetes mellitus, and dyslipidaemia, and regular alcohol consumption, should be closely monitored and controlled, since these are important risk factors for the development of liver fibrosis.
