Introduction
Alpha-1-antitripsin deficiency (AATD) is a codominant autosomal hereditary condition that predisposes patients to the development of pulmonary and/or hepatic disease, with Pi*Z mutation being the most clinically relevant.
Aims & Methods
Our aim was to evaluate the impact of AATD and Pi*Z allele in hepatic fibrosis.
Prospective, cohort, single-centred study including adult patients with AATD followed in Pneumology or Hepatology consultation. A control group was created with patients without liver disease. Liver fibrosis was assessed through non-invasive methods via serum tests, NAFLD fibrosis score (NFS) and Fibrosis-4 (FIB-4) index, and transient elastography.
Results
A total of 98 patients were included, 69 with AATD (70.4%) and 29 controls (29.6%). In the AATD group, the median value of alpha-1-antitripsin (AAT) at diagnosis was 67 mg/dL and the presence of at least one Pi*Z allele occurred in 55 patients (79.7%).
Patients with AATD regardless of genotype had a significantly higher liver stiffness measurement (LSM) compared to controls, although in both groups without significant liver fibrosis (median 5.0 vs 3.8kPa, p<0.001). Additionally, patients with AATD had significantly higher aspartate-transaminase (AST) (median 25 vs 17 UI/L, p<0.001) and alanine-transaminase (ALT) (median 29 vs 18 UI/L, p<0.001), with the two groups having values within normal range. The same occurred with alkaline phosphatase (ALP) (median 71 vs 59 UI/L, p<0.001) and gamma-glutamyl transferase (GGT) (median 25 vs 20 UI/L, p=0.007).
AAT values at diagnosis showed a negative and weak correlation with NFS (s=-0.327, p=0.007), as well as with FIB-4 index (s=-0.309, p=0.011). AAT value at diagnosis equal or superior to 77 had a sensitivity of 0.944 and specificity of 0.646 in predicting a NFS value that excludes advanced liver fibrosis (AUC 0.681; p=0.025).
In patients with at least one Pi*Z allele, the presence of diabetes mellitus was associated with 8 times higher likelihood of significant liver fibrosis with LSM≥7.1kPa (p=0.035). Furthermore, patients with at least one Pi*Z associated with both metabolic syndrome and alcohol consumption (>25 grams daily) had significantly higher NFS values (-1.18±1.45 vs -2.43±1.30, p=0.006) and FIB-4 index values (median 1.41 vs 1.0, p=0.011), being 6.55 times more likely to have an intermediate to high risk of advanced fibrosis, according to NFS (p=0.008).
Conclusion
Patients with alpha-1-antitripsin deficiency had higher liver stiffness and higher levels of serum transaminases, ALP and GGT. Alpha-1-antitripsin values at diagnosis were associated with NFS and FIB-4 index during follow-up. In patients with Pi*Z mutation, the presence of diabetes mellitus, metabolic syndrome and alcohol consumption was significantly associated with significant liver fibrosis, highlighting the need for controlling these coexisting comorbidities in this subset of patients.
