Pierre-Yves Boëlle1, Dominique Debray2,3, Loic Guillot2, Harriet Corvol4,5. 1. Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Saint-Antoine, Paris, France. 2. Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, Paris, France. 3. AP-HP, Hôpital Necker Enfants Malades, Unité d'Hépatologie Pédiatrique, Paris, France. 4. Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, Paris, France. harriet.corvol@aphp.fr. 5. AP-HP, Hôpital Trousseau, Service de Pneumologie Pédiatrique, Paris, France. harriet.corvol@aphp.fr.
Abstract
PURPOSE: The SERPINA1 Z allele is associated with cystic fibrosis (CF)-related liver disease (CFLD), a common manifestation in patients with CF. We estimated CFLD incidence based on the SERPINA1 genotype in 3328 CF patients with CFLD-phenotype information. METHODS: The associations of SERPINA1 Z (rs28929474) and S (rs17580) alleles with age at CFLD onset and the development of CFLD-related complications (severe liver disease with cirrhosis, portal hypertension, esophageal varices) were analyzed. RESULTS: Overall, 3% of patients carried the SERPINA1 Z allele and 13% carried the S allele. The cumulative incidence of CFLD increased more rapidly in patients carrying the Z allele (hazard ratio [HR] = 1.6; 95% confidence interval [CI] = 1.1-2.4, P = 0.019), reaching 47% by age 25 compared with 30% in noncarriers. Increased risk was similar for patients with severe CFLD (HR = 1.5, 95% CI = 0.7-3.2, P = 0.31) but failed to reach significance due to a limited sample size of Z-allele carriers. No significant effect was found for the S allele. CONCLUSION: CF patients carrying the SERPINA1 Z allele had an increased risk of developing CFLD and related complications compared with noncarriers. Routine SERPINA1 Z genotyping upon CF diagnosis is warranted for identifying patients worthy of closer liver disease monitoring.
PURPOSE: The SERPINA1 Z allele is associated with cystic fibrosis (CF)-related liver disease (CFLD), a common manifestation in patients with CF. We estimated CFLD incidence based on the SERPINA1 genotype in 3328 CF patients with CFLD-phenotype information. METHODS: The associations of SERPINA1 Z (rs28929474) and S (rs17580) alleles with age at CFLD onset and the development of CFLD-related complications (severe liver disease with cirrhosis, portal hypertension, esophageal varices) were analyzed. RESULTS: Overall, 3% of patients carried the SERPINA1 Z allele and 13% carried the S allele. The cumulative incidence of CFLD increased more rapidly in patients carrying the Z allele (hazard ratio [HR] = 1.6; 95% confidence interval [CI] = 1.1-2.4, P = 0.019), reaching 47% by age 25 compared with 30% in noncarriers. Increased risk was similar for patients with severe CFLD (HR = 1.5, 95% CI = 0.7-3.2, P = 0.31) but failed to reach significance due to a limited sample size of Z-allele carriers. No significant effect was found for the S allele. CONCLUSION: CF patients carrying the SERPINA1 Z allele had an increased risk of developing CFLD and related complications compared with noncarriers. Routine SERPINA1 Z genotyping upon CF diagnosis is warranted for identifying patients worthy of closer liver disease monitoring.
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