Alpha-1 antitrypsin deficiency and Pi*Z allele as important co-factors in the development of liver fibrosis

Abstract

BACKGROUND

Alpha-1 antitrypsin deficiency (AATD) is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease, and Pi*Z allele is the most clinically relevant mutation.

AIM

To evaluate the impact of clinical parameters and AATD phenotypes, particularly the Pi*Z allele, in liver fibrosis.

METHODS

Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology consultation.

RESULTS

Included 69 patients, 49.3% had Pi*MZ phenotype and 10.1% Pi*ZZ. An age ≥ 55 years, age at diagnosis ≥ 41 years and AAT at diagnosis < 77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score (NFS) not excluding advanced fibrosis [area under the curve (AUC) = 0.840, P < 0.001; AUC = 0.836, P < 0.001; AUC = 0.681, P = 0.025]. An age ≥ 50 years and age at diagnosis ≥ 41 years predicted a fibrosis-4 index of moderate to advanced fibrosis (AUC = 0.831, P < 0.001; AUC = 0.795, P < 0.001). Patients with hypertension, type 2 diabetes mellitus (DM), dyslipidaemia, metabolic syndrome, and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis (P < 0.001, P = 0.002, P = 0.008, P < 0.001, P = 0.033). Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement ≥ 7.1 kPa (P = 0.040).

CONCLUSION

Risk factors for liver disease in AATD included an age ≥ 50 years, age at diagnosis ≥ 41 years, metabolic risk factors, regular alcohol consumption, at least one Pi*Z allele, and AAT value at diagnosis < 77 mg/dL. We created an algorithm for liver disease screening in AATD patients to use in primary care, selecting those to be referred to Hepatology consultation.

Keywords: Alpha-1 antitrypsin deficiency; Liver fibrosis; Nonalcoholic fatty liver disease fibrosis score; Fibrosis-4 index; Liver stiffness measurement

Core Tip: Patients with alpha-1 antitrypsin deficiency (AATD) who have more than 50 years of age and had a diagnosis after 41 years of age are at increased risk of developing liver fibrosis, as well as those who have at least one Pi*Z allele. In patients with AATD, the presence of metabolic risk factors, such as hypertension, type 2 diabetes mellitus, and dyslipidaemia, and regular alcohol consumption, should be closely monitored and controlled, since these are important risk factors for the development of liver fibrosis.