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Meta-Analysis
. 2023 Jul;58(2):152-158.
doi: 10.1111/apt.17516. Epub 2023 Apr 23.

Meta-analysis: Prevalence of significant or advanced fibrosis in adults with alpha-1-antitrypsin deficiency

Daniel Q Huang  1   2   3 , Kai En Chan  2 , Caitlyn Tan  2 , Rebecca Wenling Zeng  2 , Benjamin Koh  2 , Elden Yen Hng Ong  2 , Charlotte Chung Hui Ong  2 , Christen En Ya Ong  2 , Darren J H Tan  2 , Wen Hui Lim  2 , Elina Cho  3 , Eunice X X Tan  2   3 , Margaret L P Teng  2   3 , Cheng Han Ng  2 , Benjamin Nah  2 , Mei Chin Lim  4 , Mark Muthiah  2   3 , Virginia C Clark  5 , Rohit Loomba  1   6
Affiliations
Meta-Analysis

Meta-analysis: Prevalence of significant or advanced fibrosis in adults with alpha-1-antitrypsin deficiency

Daniel Q Huang et al. Aliment Pharmacol Ther. 2023 Jul.

Abstract

Background: The prevalence of liver fibrosis detected by non-invasive imaging in alpha-1-antitrypsin (AAT) deficiency has not been systematically assessed.

Aims: We conducted a systematic review and meta-analysis to determine the prevalence of significant fibrosis and advanced fibrosis in AAT deficiency based on non-invasive imaging.

Methods: Medline and Embase electronic databases were searched for studies from inception to 13 November 2022 that provided data for the prevalence of fibrosis in adults with AAT deficiency. A generalised linear mixed model with Clopper-Pearson intervals was used to pool single-arm outcomes.

Results: Of the 214 records identified, 8 studies were included. Five studies assessed fibrosis using vibration-controlled transient elastography. The prevalence of significant fibrosis (defined as ≥7.1 kPA) in Z homozygosity, Z heterozygosity and non-carrier status was 22.10% (five studies, 95% CI: 17.07-28.12), 9.24% (three studies, 95% CI: 4.68-17.45) and 5.38% (one study, 95% CI: 3.27-8.73), respectively, p < 0.0001, and the prevalence of advanced fibrosis (defined as ≥9.5 kPa) was 8.13% (five studies, 95% CI: 4.60-13.96), 2.96% (three studies, 95% CI: 1.49-5.81) and 1.08% (one study, 95% CI: 0.35-3.28), respectively, p = 0.003. There were limited data regarding the use of magnetic resonance elastography or acoustic radiation force impulse to assess for fibrosis.

Conclusion: More than one in five adult individuals with AAT deficiency and Z homozygosity harbour significant fibrosis, and nearly 1 in 10 harbours advanced fibrosis. The risk of fibrosis increases incrementally with the frequency of Pi*Z mutations.

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Conflict of interest statement

R.L. serves as a consultant or advisory board member for Anylam/Regeneron, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse Bio, Inipharm, Intercept, Ionis, Janssen, Merck, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Promethera, Sagimet, 89bio, and Viking Therapeutics. In addition, his institution has received grant support from Allergan, Boehringer-Ingelheim, Bristol-Myers Squibb, Cirius, Eli Lilly and Company, Galectin Therapeutics, Galmed Pharmaceuticals, Genfit, Gilead, Intercept, Inventiva, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Pfizer, pH Pharma, and Siemens. He is also co-founder of Liponexus. D.H serves as an advisory board member for Eisai. P.M serves as a consultant of advisory member for Ipsen, Eisai, Abbvie, Sanofi, Gilead Sciences, Evive Biotech, Novo Nordisk, Bayer Healthcare, Intercept, Surrozen, and Pfizer. H.C.P lectures and receives advisory board fees from Intercept, Genfit, Promethera Bioscience, Orphalan, Novo Nordisk and Roche Portugal.

Figures

Figure 1.
Figure 1.
PRISMA flowchart
Figure 2.
Figure 2.
Prevalence of (A) significant fibrosis and (B) advanced fibrosis in adults with alpha-1-antitrypsin deficiency Abbreviations: LSM, liver stiffness measurement
Figure 2.
Figure 2.
Prevalence of (A) significant fibrosis and (B) advanced fibrosis in adults with alpha-1-antitrypsin deficiency Abbreviations: LSM, liver stiffness measurement
See this image and copyright information in PMC

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