Background & Aims: Patients with Alpha-1 Antitrypsin Deficiency (AATD) have a 20to 50-fold higher risk of developing primary liver cancer (PLC), such as hepatocellular carcinoma (HCC), in both cirrhotic and non-cirrhotic 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 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 non-tumoral 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 non-cirrhotic livers, highlighting their potential relevance for further investigation.
Beaufrère et al. (Wed,) studied this question.