未经证实:多囊肝病(PLD)表现为散布在整个肝实质中的许多充满液体的囊肿。PLD最常见于女性,作为常染色体显性多囊肾病(ADPKD)的肾外表现或孤立的常染色体显性多囊性肝病(ADPLD)。尽管已知遗传原因,临床变异性对患者咨询提出了挑战,缺乏基因型-表型相关性和预后成像分类,阻碍了及时的风险预测.
UNASSIGNED:我们进行了靶向下一代测序和多重连接依赖性探针扩增,以确定80名深度特征PLD患者的潜在遗传缺陷。鉴定的基因型与总的肝和肾体积相关(通过CT或MRI评估),器官功能,合并症,和临床终点。
未经证实:在60(75%)患者中发现了单等位基因诊断变异,其中38(48%)与ADPKD基因变体(PKD1,PKD2,GANAB)有关,22(27%)与ADPLD基因变体(PRKCSH,SEC63).与没有遗传诊断的患者相比,突变携带者在等待肝移植和首次PLD相关住院时的年龄定义的疾病严重程度明显更明显。虽然目前的影像学分类无法区分重度和中度病程,通过估计的年龄校正后的总肝脏体积进展进行分组,产生了显著的风险区分.
UNASSIGNED:本研究强调了为PLD患者提供分子诊断的预测价值。此外,我们提出了一种基于年龄和身高调整后的肝脏总体积的新型风险分类模型,该模型可以改善个体预后和个性化临床管理.
UNASSIGNED:多囊肝病(PLD)是一种高度可变的疾病,可以无症状或严重。然而,目前很难预测临床结果,如住院,症状负担,以及个别患者需要移植。在目前的研究中,我们的目的是探讨基因确认和年龄校正后的总肝脏体积分类对个体疾病预测的临床价值.虽然遗传确认通常指向更严重的疾病,估计年龄调整后的肝脏体积增加可能有助于预测临床结局.
UNASSIGNED: Polycystic liver disease (PLD) manifests as numerous fluid-filled cysts scattered throughout the liver parenchyma. PLD most commonly develops in females, either as an extra-renal manifestation of autosomal-dominant polycystic kidney disease (ADPKD) or as isolated autosomal-dominant polycystic liver disease (ADPLD). Despite known genetic causes, clinical variability challenges patient counselling and timely risk prediction is hampered by a lack of genotype-phenotype correlations and prognostic imaging classifications.
UNASSIGNED: We performed targeted next-generation sequencing and multiplex ligation-dependent probe amplification to identify the underlying genetic defect in a cohort of 80 deeply characterized patients with PLD. Identified genotypes were correlated with total liver and kidney volume (assessed by CT or MRI), organ function, co-morbidities, and clinical endpoints.
UNASSIGNED: Monoallelic diagnostic variants were identified in 60 (75%) patients, 38 (48%) of which pertained to ADPKD-gene variants (PKD1, PKD2, GANAB) and 22 (27%) to ADPLD-gene variants (PRKCSH, SEC63). Disease severity defined by age at waitlisting for liver transplantation and first PLD-related hospitalization was significantly more pronounced in mutation carriers compared to patients without genetic diagnoses. While current imaging classifications proved unable to differentiate between severe and moderate courses, grouping by estimated age-adjusted total liver volume progression yielded significant risk discrimination.
UNASSIGNED: This study underlines the predictive value of providing a molecular diagnosis for patients with PLD. In addition, we propose a novel risk-classification model based on age- and height-adjusted total liver volume that could improve individual prognostication and personalized clinical management.
UNASSIGNED: Polycystic liver disease (PLD) is a highly variable condition that can be asymptomatic or severe. However, it is currently difficult to predict clinical outcomes such as hospitalization, symptom burden, and need for transplantation in individual patients. In the current study, we aimed to investigate the clinical value of genetic confirmation and an age-adjusted total liver volume classification for individual disease prediction. While genetic confirmation generally pointed to more severe disease, estimated age-adjusted increases in liver volume could be useful for predicting clinical outcomes.