Aini Haddouche1, Christine Bellanne-Chantelot2, Anne Rod1, Luc Fournier3, Laurence Chiche4, Jean-Francois Gautier5, Jose Timsit6, Sandrine Laboureau7, Lucy Chaillous8, Rene Valero9, Etienne Larger6, Nathalie Jeandidier10, Jean-Marie Wilhelm11, Marc Popelier12, Pierre-Jean Guillausseau13, Charles Thivolet14, Pierre Lecomte15, Pierre-Yves Benhamou16, Yves Reznik1. 1. Department of Endocrinology and Diabetology, Caen University Hospital, Caen, France. 2. Department of Genetics, Pitié-Salpetrière Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris, France. 3. Department of Radiology, Caen University Hospital, Caen, France. 4. Department of Hepatobiliary and Pancreatic Surgery, Bordeaux University Hospital, Maison du Haut Lévèque, Bordeaux, France. 5. Department of Endocrinology and Diabetology, Saint Louis University Hospital, Paris, France. 6. Department of Immunology and Diabetology, Cochin University Hospital, Paris, France. 7. Department of Endocrinology and Diabetology, Angers University Hospital, Angers, France. 8. Department of Endocrinology, Hôtel Dieu University Hospital, Nantes, France. 9. Department of Nutrition and Metabolic Diseases, La Conception Hospital, Marseille, France. 10. Department of Endocrinology, Diabetology and Metabolic Diseases, Leriche Pavillon, Civil Hospital, Strasbourg, France. 11. Department of Medicine, Saint Morand Hospital, Altkirch, France. 12. Department of Medicine, Pitié-Salpetrière Hospital, Paris, France. 13. Department of Medicine B6, Lariboisière University Hospital, Paris, France. 14. Department of Endocrinology and Metabolic Diseases, Debrousse University Hospital, Lyon, France. 15. Department of Endocrinology and Diabetology, Bretonneau University Hospital, Tours, France. 16. Department of Diabetology, Endocrinology and Nutrition, Grenoble University Hospital, Grenoble, France.
Abstract
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.
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.
Authors: Martijn P D Haring; Titia M Vriesendorp; Jolien S Klein Wassink-Ruiter; Robbert J de Haas; Annette S H Gouw; Vincent E de Meijer Journal: Liver Int Date: 2019-09-13 Impact factor: 5.828