Factors associated with the development of liver-related endpoints in adults with severe alpha-1 antitrypsin deficiency (Pi*ZZ genotype)

Aims and objectives Homozygous Pi*Z mutation (Pi*ZZ genotype) confers a strong predisposition for the development of lung and liver disease. Since the pace of liver disease progression and prognostic factors remain unknown, we evaluated host-related risk factors in the European Pi*ZZ liver cohort.

Methods 546 Pi*ZZ subjects without concomitant liver diseases, previous liver decompensation, or pathological alcohol consumption received a baseline clinical, laboratory, and elastographic assessment. 491 of them had a detailed follow-up interview at least six months after their baseline examination.

Results At baseline, 26% and 13% of Pi*ZZ individuals presented with a liver stiffness suggestive of significant and advanced fibrosis, respectively. 12% had a BMI>30kg/m2 and 3% suffered under diabetes mellitus. During a median follow-up of 3.7 years, 26 individuals developed an hepatic endpoint (liver transplant/death, or decompensated cirrhosis). Pi*ZZ individuals with hepatic endpoint showed a significantly higher BMI (28 vs. 24 kg/m2, p=2.7x10-4), were more often male (77 vs. 53%, p=.018) and presented more often with diabetes mellitus (15 vs. 3%, p=7.9x10-4) at baseline, while no significant difference in alcohol consumption was noted. Cox regression analysis revealed diabetes mellitus (HR 5.7, 95% CI 1.9-16.6, p=.002) and BMI>30 kg/m2 (HR 4.4, 95% CI 1.9-10.3, p=6.8x10-4) as strong metabolic risk factors for liver-related endpoints. Male gender constituted a moderate risk factor (HR 3.0, 95% CI 1.2-7.4, p=.021), while age>50 years did not reach significance.

Conclusions In Pi*ZZ individuals, the presence of diabetes mellitus and BMI>30 kg/m2 are strongly associated with the development of liver-related endpoints.

Publication History

Article published online:
23 January 2024