Heterozygotes for Z or S alleles of alpha-1-antrypsin (AAT) have low serum AAT levels. Our aim was to compare the risk of hepatocellular carcinoma (HCC) in patients with liver cirrhosis carrying the SERPINA1 MM, MZ and MS genotypes. The study groups consisted of 1119 patients with liver cirrhosis of various aetiologies, and 3240 healthy individuals served as population controls. The MZ genotype was significantly more frequent in the study group (55/1119 vs. 87/3240, p < 0.0001). The MS genotype frequency was comparable in controls (32/119 vs. 101/3240, p = 0.84). MZ and MS heterozygotes had lower serum AAT level than MM homozygotes (medians: 0.90 g/L; 1.40 g/L and 1.67 g/L; p < 0.001 for both). There were significantly fewer patients with HCC in the cirrhosis group among MZ and MS heterozygotes than in MM homozygotes (5/55 and 1/32 respectively, vs. 243/1022, p < 0.01 for both). The risk of HCC was lower in MZ and MS heterozygotes than in MM homozygotes (OR 0.3202; 95% CI 0.1361-0.7719 and OR 0.1522; 95% CI 0.02941-0.7882, respectively). Multivariate analysis of HCC risk factors identified MZ or MS genotype carriage as a protective factor, whereas age, male sex, BMI and viral aetiology of cirrhosis increased HCC risk.

1st Faculty of Medicine Charles University 120 00 Prague Czech Republic

Anaesthesiology and Resuscitation Department Institute for Clinical and Experimental Medicine 140 21 Prague Czech Republic

Atherosclerosis Research Laboratory Institute for Clinical and Experimental Medicine 140 21 Prague Czech Republic

Clinical and Transplant Pathology Department Institute for Clinical and Experimental Medicine 140 21 Prague Czech Republic

Department of Hepatogastroenterology Institute for Clinical and Experimental Medicine 140 21 Prague Czech Republic

Department of Internal Medicine 1st Faculty of Medicine Charles University and Military University Hospital 160 00 Prague Czech Republic

Institute of Medical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine Charles University 120 00 Prague Czech Republic

Laboratory of Experimental Hepatology Experimental Medicine Centre Institute for Clinical and Experimental Medicine 140 21 Prague Czech Republic

Preventive Cardiology Centre Institute for Clinical and Experimental Medicine 140 21 Prague Czech Republic

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Genetic drivers of liver cirrhosis: The role of SERPINA1 and PNPLA3 variants in disease onset and progression

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