Hepatocellular adenoma management: call for shared guidelines and multidisciplinary approach.

Hepatocellular adenomas are rare benign nodules developed mainly in women taking oral contraceptives. They are solitary or multiple. Their size is highly variable. There is no consensus in the literature for their management except that once their size exceeds 5 cm nodules are taken out to prevent 2 major complications: bleeding and malignant transformation. There are exceptions particularly in men where it is recommended to remove smaller nodules. Since the beginning of this century, major scientific contributions have unveiled the heterogeneity of the disease. HCA are composed of four major subtypes. HNF1A (coding for hepatocyte nuclear factor 1a) inactivating mutations (H-HCA); inflammatory adenomas (IHCA); the β-catenin-mutated HCAs (β-HCA) and unclassified HCA (UHCA) occurring in 30-40%, 40-50%, 10-15% and 10% of all HCA, respectively. Half of β-HCAs are also inflammatory (β-IHCA). Importantly, β-catenin mutations are associated with a high risk of malignant transformation. HCA subtypes can be identified on liver tissue, including biopsies using specific immunomarkers with a good correspondence with molecular data. Recent data has shown that TERT promoter mutation was a late event in the malignant transformation of β-HCA, β-IHCA. Furthermore, in addition to β-catenin exon 3 mutations, other mutations do exist (exon 7 and 8) with a lower risk of malignant transformation. With these new scientific informations, we have the tools to better know the natural history of the different subtypes, in terms of growth, disappearance, bleeding, malignant transformation and to investigate HCA in diseased livers (vascular diseases, alcoholic cirrhosis). A better knowledge of HCA should lead to a more rational management of HCA. This can be done only if the different subspecialties, including hepatologists, liver pathologists, radiologists and surgeons work altogether in close relationship with molecular biologists. It is a long way to go.