Liver adenomatosis in patients with hepatocyte nuclear factor-1 alpha maturity onset diabetes of the young (HNF1A-MODY): Clinical, radiological and pathological characteristics in a French series
Liver adenomatosis in patients with hepatocyte nuclear factor-1 alpha maturity onset diabetes of the young (HNF1A-MODY): Clinical, radiological and pathological characteristics in a French series
复制标题
DOI：
10.1111/1753-0407.12959
复制
发表时间：
2019-07-10
影响因子：
4.5
通讯作者：
Reznik, Yves
中科院分区：
文献类型：
--
作者：
Haddouche, Aini;Bellanne-Chantelot, Christine;Reznik, Yves
背景肝腺瘤病（Liver adenomatosis，LA）是一种罕见的肝细胞核因子-1 α（hepatocyte nuclear factor-1 alpha，HNF 1A）基因双等位基因失活引起的肝腺瘤病。肝腺瘤病仅在携带HNF 1A生殖系突变的患者的病例报告中有记载。我们评估了一个大型队列的HNF 1A-成熟型青年糖尿病（MODY），以前称为“MODY 3”，患者中LA的频率，并在此描述其临床，放射学和病理学特征。方法在13个中心对74个家系的137例HNF 1A-MODY患者进行肝脏超声筛查，并将15例LA患者纳入研究。通过肝脏计算机断层扫描、磁共振成像（MRI）和/或组织病理学证实肝腺瘤病。结果137例HNF 1A基因突变携带者中，7个家系中9例（6.5%）确诊为LA。87.5%的LA患者存在糖尿病。在25%的患者中，LA被诊断为腹腔内或肿瘤内出血。所有患者的肝脏生化接近正常。肝脏成像显示各种大小和数量的腺瘤。在MRI上，大多数结节具有脂肪性腺瘤的放射学特征。在13例病例中，组织学证实了LA，这些腺瘤大多为脂肪变性。37.5%的患者最初进行了手术，30%的患者观察到肝脏疾病进展。在14例妊娠中未观察到疾病进展。结论HNF 1A-MODY筛查患者队列中LA的发生率以及LA进展和/或出血的高发生率，需要对HNF 1A-MODY家族中的肝腺瘤病进行系统筛查。
Background Liver adenomatosis (LA) is a rare disease resulting from biallelic inactivation of the hepatocyte nuclear factor-1 alpha (HNF1A) gene, which induces the proliferation of adenoma cells in liver parenchyma. Liver adenomatosis has only been documented in case reports from patients carrying a HNF1A germline mutation. We have evaluated the frequency of LA among a large cohort of patients with HNF1A-maturity onset diabetes of the young (MODY), previously termed "MODY3," and herein describe its clinical, radiological, and pathological characteristics. Methods In all, 137 HNF1A-MODY subjects from 74 families were screened by liver ultrasonography in 13 centers, and 15 additional cases of LA were later included in the series. Liver adenomatosis was confirmed by liver computed tomography, magnetic resonance imaging (MRI), and/or histopathology. Results Among 137 carriers of an HNF1A mutation, 9 patients (6.5%) from seven families were diagnosed with LA. Diabetes mellitus was present in 87.5% of patients with LA. In 25% of patients, LA was diagnosed due to intra-abdominal or intratumoral bleeding. Liver biochemistry was near normal in all patients. Liver imaging showed adenomas of various sizes and numbers. On MRI, most nodules had the radiological characteristics of steatotic adenomas. Histopathological confirmation of LA was available in 13 cases, and these adenomas were mostly steatotic. Surgery was initially performed in 37.5% of patients, and liver disease progression was observed in 30%. No disease progression was observed in 14 pregnancies. Conclusions The frequency of LA in a cohort of screened HNF1A-MODY patients and the high incidence of LA progression and/or hemorrhage warrants systematic screening for liver adenomatosis in HNF1A-MODY families.