In 90% of the cases, adenomas are sporadic and only rare cases are developed in a familial context: ( Familial liver adenomatosis). Patients with an inherited mutation in one allele of TCF1/HNF1a may develop maturity onset diabetes of the young type 3 (MODY3) and familial liver adenomatosis, when the second allele is inactivated in hepatocytes by somatic mutation or chromosome deletion.

Hepatocellular adenomas are usually related to oral contraceptive use. The other risk factors are : glycogen storage diseases and the androgen therapy. HA are rare tumours: their estimated incidence in France is approximately one case per 100,000 women. Over the past fifteen years, their incidence has seen a sustained decline in industrialised countries; this trend is probably linked to the reduction in ethinylestradiol doses in oral contraceptives.

These tumours result from a benign proliferation of hepatocytes which destroy the normal architecture of the liver. They are usually hyper-vascularised and typical adenoma corresponds to a proliferation of benign hepatocytes, intermingled with numerous thin-walled vessels, without portal tracts.

Surgery is usually proposed for lesion of more than 3 cm

Hepatocellular adenoma may bleed, or rarely, undergo malignant transformation.

The molecular and pathological classification of hepatocellular adenomas permits the identification of strong genotype-phenotype correlations and suggests that adenomas with beta-catenin activation have a higher risk of malignant transformation.

Germline TCF1/HNF1A mutation can predispose to familial liver adenomatosis

HNF1A (HNF1 homeobox A)

12q24.31

Alias: HNF1A, hepatocyte nuclear factor 1 alpha, HNF1, LFB1, M57732, MODY3

CTNNB1 (Catenin, beta-1)

3p22.1

Description: catenin (cadherin-associated protein), beta 1

Beta-catenin is an adherens junction protein. Adherens junctions are critical for the establishment and maintenance of epithelial layers, cells adhesion, signal communication, anchorage of the actin cytoskeleton. CTNNB1 has important functions in the E-cadherin-mediated cell-cell adhesion system and also as a dowstream signaling molecule in the Wnt pathway. Cytoplasmic accumulation of b catenin allows it to translocate to the nucleus to form complexes with transcription factors of the T cell factor-lymphoid enhancer factor (Tcf-Lef) family. b-catenin is assumed to transactivate mostly unknown target genes, which may stimulate cell proliferation (acts as an oncogene) or inhibit apoptosis. The b-catenin level in the cell is regulated by its association with the adenomatous polyposis coli ( APC) tumor suppressor protein, axin and GSK-3b. Phosphorylation of b-catenin by the APC-axin-GSK-3b complex leads to its degradation by the ubiquitin-proteasome system.