Evidence map›Paper›PMID 42437373›Full record

SynthesisAlimentary pharmacology & therapeutics2026

Meta-Analysis: Redefining Liver Disease Risk in Heterozygous Alpha-1 Antitrypsin Deficiency.

Adam M Syanda, Dimitra Georgantaki, Riona T T Linn, Amara Agbai, Hassan Tahir, Manako Sakai, Richard Thompson, Mariam Molokhia, S Tamir Rashid

Abstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in Alimentary pharmacology & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Adam M SyandaDepartment of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK.ORCID https://orcid.org/0000-0003-2297-6146
Dimitra GeorgantakiDepartment of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK.
Riona T T LinnFaculty of Medicine, Imperial College London, London, UK.
Amara AgbaiFaculty of Medicine, Imperial College London, London, UK.
Hassan TahirFaculty of Medicine, Imperial College London, London, UK.
Manako SakaiDepartment of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK.
Richard ThompsonInstitute of Liver Studies, King's College London, London, UK.
Mariam MolokhiaDepartment of Population Health Sciences, School of Life Course and Population Sciences, King's College London, London, UK.
S Tamir RashidDepartment of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHeterozygous SERPINA1 genotypes (MZ, SZ) have historically been regarded as carrier states with limited liver relevance. Emerging evidence suggests increased liver injury, but the magnitude of risk remains uncertain. We synthesized evidence on heterozygous SERPINA1 liver phenotypes to quantify this risk.

methodsWe performed a systematic review of bibliographic databases from inception to 21 October 2025 for studies reporting liver outcomes in MZ or SZ genotypes. Outcomes were grouped into metabolic comorbidities, biochemical markers, and clinical liver disease. Random-effects meta-analyses pooled mean differences (MDs) and odds ratios (ORs); risk of bias was assessed with established tools (PROSPERO CRD420251165586).

resultsTwenty-six studies including 27,933 heterozygotes and 547,961 controls met inclusion criteria. BMI (MD -0.09 [-0.20-0.02]) and steatosis risk (OR 1.09 [0.74-1.60]) were comparable between groups. Heterozygotes had modestly higher liver enzymes (ALT MD 1.03 [0.41-1.66]; AST MD 0.68 [0.51-0.85]; ALP MD 2.58 [1.58-3.58]) and higher odds of abnormal ALT (OR 1.18 [1.11-1.25]), AST (OR 1.16 [1.07-1.26]), and ALP (OR 1.41 [1.18-1.68]). They had significantly increased odds of fibrosis (OR 2.14 [1.52-3.02]), cirrhosis (OR 2.24 [1.73-2.91]), and liver transplantation (OR 2.28 [1.45-3.59]).

conclusionsHeterozygous SERPINA1 genotypes are bona fide liver risk states, with effect sizes comparable to established genetic and environmental determinants. MZ/SZ heterozygosity should be recognized as moderate-penetrance liver susceptibility genotypes in chronic liver disease risk assessment.

Indexed as

alpha 1-Antitrypsinalpha 1-Antitrypsin DeficiencyLiver DiseasesGenotypeHeterozygoteHumansPhenotypeRisk Factorsalpha 1-AntitrypsinSERPINA1 protein, humanA1ATDalpha‐1 antitrypsin deficiencyheterozygous MZheterozygous SZliver cirrhosisliver diseaseliver fibrosismeta‐analysisSERPINA1steatosis

Identifiers

PMID42437373
PMCPMC13419271

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.