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.
背景: 肝细胞腺瘤病(liver adenomatosis, LA)是一种由于肝细胞核因子-1α(HNF1A)基因中的双等位基因失活所导致的罕见疾病, 可诱发肝实质中的腺瘤细胞增殖。肝细胞腺瘤病仅见于携带HNF1A种系突变基因患者的病例报告。我们在一个大型HNF1A-青少年发病的成年型糖尿病(MODY, 以前被称为“MODY3”)患者队列中评估了LA的发生率, 并在此对其临床、放射学以及病理学特征进行了描述。 方法: 共有137名来自于74个家系的HNF1A-MODY受试者在13个中心接受了肝脏超声检查, 后续还有15名LA患者被纳入这项系列研究。通过肝脏计算机断层扫描、磁共振成像(MRI)和/或组织病理学检查来确诊肝细胞腺瘤病。 结果: 在137名HNF1A突变基因携带者中, 来自7个家系的9例(6.5%)患者被诊断为LA。87.5%的LA患者存在糖尿病。25%的患者因出现腹腔内或者肿瘤内出血而被诊断为LA。所有患者的肝脏生化指标均接近正常。肝脏影像学表现为大小不等、数目不等的腺瘤。在MRI上, 大多数结节具有脂肪性腺瘤的影像学特征。13例LA得到组织病理学证实, 并且这些腺瘤以脂肪变性为主。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。14例妊娠患者未见疾病进展。 结论: 在筛选的HNF1A-MODY患者队列中, 由于LA的高发病率以及LA进展和/或出血的高发生率, 因此很有必要在HNF1A-MODY家系中进行肝细胞腺瘤病的系统筛查。.
Keywords: HNF1A-MODY; diabetes mellitus; liver adenomatosis; 糖尿病; 肝细胞腺瘤病.
© 2019 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.