PhD ceremony Ms. J. Han: The microenvironment of the inflammatory type hepatocellular adenoma

PhD ceremony: Ms. J. Han

Dissertation: The microenvironment of the inflammatory type hepatocellular adenoma

Promotor(s): prof. A.S.H. Gouw, prof. G. Molema

Faculty: Medical Sciences

Benign hepatocellular tumours are characterized by a hepatocyte proliferation without invasion and metastasis. Hepatocellular adenoma (HCA) is a benign tumour arising in an otherwise non-diseased liver with an incidence of 3-4/100,000 people with long term use of oral contraceptives. It is the second most common hepatocellular benign tumour next to focal nodular hyperplasia (FNH). HCA sub-typing is based on the genotypes and the inflammatory HCA (IHCA), which is associated with overweight/obesity, is the most frequent subtype of HCA.

In this thesis, we investigated the microenvironment in which IHCA develops and explored the possible molecular link between obesity with IHCA. We found foci of micro-adenomas in the non-lesional liver and frequent presence of steatosis suggesting that the liver in which IHCA develops can be regarded as a “sick” liver. When we analysed the status of adipokines receptors in IHCA we found an increased expression of leptin-receptor and decreased adiponectin-receptor in the tumour which may stimulate tumour growth and induce the inflammatory phenotype of IHCA via leptin/leptin-receptor activation. These findings may represent the link of IHCA with obesity due to hyperleptinemia and hypoadiponectinemia in obesity. We also investigated the nature of biliary ductules in IHCA and found that they represent hepatic progenitor cells (HPC) mediated regeneration associated with the inflammation within IHCA. We also found subclonal cell populations in the tumour that probably are generated by stem cells, independent of the inflammatory status.

Summarizing, the liver in which IHCA develops harbours microadenomas and obesity may contribute to the growth and IHCA phenotype.