We analyzed an international multicenter cohort of 265 patients with autosomal dominant polycystic liver disease harboring pathogenic variants in PRKCSH or SEC63 for genotype-phenotype correlations, including normalized age-adjusted total liver volumes and polycystic liver disease-related hospitalization (liver event) as primary clinical end points.
Classifying individual total liver volumes into predefined progression groups yielded predictive risk discrimination for future liver events independent of sex and underlying genetic defects. In addition, disease severity, defined by age at first liver event, was considerably more pronounced in female patients and patients with PRKCSH variants than in those with SEC63 variants. A newly developed sex-gene score was effective in distinguishing mild, moderate, and severe disease, in addition to imaging-based prognostication.
Both imaging and clinical genetic scoring have the potential to inform patients about the risk of developing symptomatic disease throughout their lives. The combination of female sex, germline PRKCSH alteration, and rapid total liver volume progression is associated with the greatest odds of polycystic liver disease-related hospitalization.
方法:我们分析了一个由265例携带PRKCSH或SEC63致病变异的ADPLD患者组成的多中心队列的基因型-表型相关性,包括标准化的年龄校正的总肝脏体积(nTLV)和PLD相关住院(肝脏事件)作为主要临床终点.
结果:将个体nTLV分类为预定义的进展组,可预测未来肝脏事件的风险区分,与性别和潜在的遗传缺陷无关。此外,疾病严重程度,由第一次肝脏事件的年龄定义,在女性和PRKCSH变异的患者中,比SEC63变异的患者更明显。新开发的性别基因评分可有效区分轻度,中度,和严重的疾病,除了基于成像的预后。
结论:影像学和临床遗传评分都有可能告知患者一生中发生症状性疾病的风险。女性的结合,种系PRKCSH改变,快速的TLV进展与PLD相关住院的最大几率相关。