Alpha-1 Antitrypsin Deficiency Alleles in Non-Cirrhotic Hepatocellular Carcinoma: Insights from a Multicenter French Cohort
Abstract
Background and aims: Patients with alpha-1 antitrypsin deficiency (AATD) have a 20-to 50-fold higher risk of developing primary liver cancer (PLC), such as hepatocellular carcinoma (HCC), in both cirrhotic and noncirrhotic livers, highlighting AATD as a potential oncogenic factor. In this exploratory study, we aimed to describe the frequency and characteristics of AATD alleles in patients with HCC arising in noncirrhotic livers. Methods: The two most common pathogenic AATD variants, the Z (SERPINA1 p.Glu366Lys) and S (SERPINA1 p.Glu264Val) alleles, were identified using a multiplex digital polymerase chain reaction (PCR) system in a French cohort of 91 patients who developed HCC in a noncirrhotic liver and without major liver risk factors, including alcohol consumption, viral hepatitis, or metabolic-associated steatohepatitis. Results: We found that 22.83% (21/91) of patients with HCC carried at least one S or Z allele of SERPINA1, a prevalence that was higher than in the general French population (16.9%) and in the UK population with PLC (12%). The distribution of genotypes was heterozygous for the M and S alleles (18/21), heterozygous for the M and Z alleles (2/ 21), and homozygous for the S allele (1/21). Interestingly, AAT globules were observed in nontumoral liver tissue in 7 cases (37%), including individuals heterozygous for the M and S alleles and the individual homozygous for the S allele. Conclusion: Our study provides descriptive data on the presence of S and Z variants of SERPINA1 in patients with HCC arising in noncirrhotic livers, highlighting their potential relevance for further investigation.
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BibTeX
@article{beaufrere2026alpha1,
title = {{Alpha-1 Antitrypsin Deficiency Alleles in Non-Cirrhotic Hepatocellular Carcinoma: Insights from a Multicenter French Cohort}},
author = {Aurélie Beaufrère and Celine Leon and Marie Decreaker and Laurent Possenti and Manon Evain and Audrey Coilly and Carolin V Schneider and Zoé Feurer and Marie-Françoise Odou and Malika Balduyck and Audrey Payancé and Kai M Schneider and Paulette Bioulac and Jean-Frédéric Blanc and Brigitte Le Bail and Catherine Guettier and Samuel Amintas and Marion Bouchecareilh},
journal = {Journal of Clinical and Experimental Hepatology},
year = {2026},
month = oct,
doi = {10.1016/j.jceh.2026.103545},
url = {https://amu.hal.science/hal-05775005v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Alpha-1 Antitrypsin Deficiency Alleles in Non-Cirrhotic Hepatocellular Carcinoma: Insights from a Multicenter French Cohort
AU - Aurélie Beaufrère
AU - Celine Leon
AU - Marie Decreaker
AU - Laurent Possenti
AU - Manon Evain
AU - Audrey Coilly
AU - Carolin V Schneider
AU - Zoé Feurer
AU - Marie-Françoise Odou
AU - Malika Balduyck
AU - Audrey Payancé
AU - Kai M Schneider
AU - Paulette Bioulac
AU - Jean-Frédéric Blanc
AU - Brigitte Le Bail
AU - Catherine Guettier
AU - Samuel Amintas
AU - Marion Bouchecareilh
PY - 2026
DA - 2026/10/02
JO - Journal of Clinical and Experimental Hepatology
DO - 10.1016/j.jceh.2026.103545
UR - https://amu.hal.science/hal-05775005v1
AB - Background and aims: Patients with alpha-1 antitrypsin deficiency (AATD) have a 20-to 50-fold higher risk of developing primary liver cancer (PLC), such as hepatocellular carcinoma (HCC), in both cirrhotic and noncirrhotic livers, highlighting AATD as a potential oncogenic factor. In this exploratory study, we aimed to describe the frequency and characteristics of AATD alleles in patients with HCC arising in noncirrhotic livers. Methods: The two most common pathogenic AATD variants, the Z (SERPINA1 p.Glu366Lys) and S (SERPINA1 p.Glu264Val) alleles, were identified using a multiplex digital polymerase chain reaction (PCR) system in a French cohort of 91 patients who developed HCC in a noncirrhotic liver and without major liver risk factors, including alcohol consumption, viral hepatitis, or metabolic-associated steatohepatitis. Results: We found that 22.83% (21/91) of patients with HCC carried at least one S or Z allele of SERPINA1, a prevalence that was higher than in the general French population (16.9%) and in the UK population with PLC (12%). The distribution of genotypes was heterozygous for the M and S alleles (18/21), heterozygous for the M and Z alleles (2/ 21), and homozygous for the S allele (1/21). Interestingly, AAT globules were observed in nontumoral liver tissue in 7 cases (37%), including individuals heterozygous for the M and S alleles and the individual homozygous for the S allele. Conclusion: Our study provides descriptive data on the presence of S and Z variants of SERPINA1 in patients with HCC arising in noncirrhotic livers, highlighting their potential relevance for further investigation.
SN - 0973-6883
ER -