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.

中文翻译：

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SERPINA1 Z 等位基因与囊性纤维化肝病相关。

目的 SERPINA1 Z 等位基因与囊性纤维化 (CF) 相关肝病 (CFLD) 相关，这是 CF 患者的常见表现。我们根据 3328 名具有 CFLD 表型信息的 CF 患者的 SERPINA1 基因型估计了 CFLD 的发病率。方法分析SERPINA1 Z（rs28929474）和S（rs17580）等位基因与CFLD发病年龄和CFLD相关并发症（严重肝病伴肝硬化、门静脉高压、食管静脉曲张）发展的关系。结果 总体而言，3% 的患者携带 SERPINA1 Z 等位基因，13% 的患者携带 S 等位基因。在携带 Z 等位基因的患者中，CFLD 的累积发病率增加得更快（风险比 [HR] = 1.6；95% 置信区间 [CI] = 1.1-2.4，P = 0.019），到 25 岁时达到 47%，而 30%在非运营商。严重 CFLD 患者的风险增加相似（HR = 1.5, 95% CI = 0.7-3.2, P = 0.31），但由于 Z 等位基因携带者的样本量有限，未能达到显着性。S等位基因没有发现显着影响。结论 与非携带者相比，携带 SERPINA1 Z 等位基因的 CF 患者发生 CFLD 和相关并发症的风险增加。CF 诊断时的常规 SERPINA1 Z 基因分型对于识别值得密切监测肝病的患者是必要的。