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.

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.

• Authors: Aini Haddouche, Christine Bellanne-Chantelot, Anne Rod, Luc Fournier, Laurence Chiche, Jean-Francois Gautier, Jose Timsit, Sandrine Laboureau, Lucy Chaillous, Rene Valero, Etienne Larger, Nathalie Jeandidier, Jean-Marie Wilhelm, Marc Popelier, Pierre-Jean Guillausseau, Charles Thivolet, Pierre Lecomte, Pierre-Yves Benhamou, Yves Reznik
• Journal: Journal of diabetes (J Diabetes) Vol. 12 Issue 1 Pg. 48-57 (Jan 2020) ISSN: 1753-0407 [Electronic] Australia
• PMID: 31166087 (Publication Type: Journal Article, Multicenter Study)
• Copyright: © 2019 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Chemical References

• HNF1A protein, human
• Hepatocyte Nuclear Factor 1-alpha

Topics

• Adenoma (diagnostic imaging, genetics, pathology)
• Adolescent
• Adult
• Child
• Cohort Studies
• Diabetes Mellitus, Type 2 (diagnostic imaging, genetics, pathology)
• Diagnostic Imaging (methods)
• Family Health
• Female
• France
• Hepatocyte Nuclear Factor 1-alpha (genetics, metabolism)
• Humans
• Liver Neoplasms (diagnostic imaging, genetics, pathology)
• Male
• Middle Aged
• Mutation
• Young Adult