Hepatocellular adenoma (HCA) is a benign neoplasm arising from hepatocytes. There is evidence that the inflammatory subtype may be associated with obesity and alcohol use and that men with metabolic syndrome may be at risk for malignant transformation of HCA. We sought to explore the combined experience of US centers as reported in the literature to document the epidemiologic shift in risk factors for HCA formation in the United States, namely, a shift from oral contraceptive pills (OCPs) to an emerging role of obesity as a contributing factor. Methods. Publications reporting HCA in the United States were identified through a PubMed search and a review of the literature. We excluded publications prior to 1970, single case reports, and publications for which there was no data available regarding patient characteristics including OCP use and the number of adenomas. Conclusion. Whereas earlier reports of HCA in the United States described cases exclusively in women exposed to OCPs, there is a trend towards an increase in HCAs reported in men, HCAs in the absence of OCP use, and increased reporting of multiple HCAs. This may be a result of newer OCP formulations and increasing prevalence of obesity. 1. Introduction Hepatocellular adenomas (HCAs) are benign hepatic neoplasms that became widely recognized in the 1960s and 1970s following the introduction of oral contraceptive pills (OCP’s). Recent advances have identified distinct subtypes based on genotypic classification [1]. These types are (1) hepatocyte nuclear factor-1α (HNF-1α)-mutated HCAs (H-HCA), (2) β-catenin-mutated HCAs (b-HCA), (3) inflammatory HCAs (I-HCA) (which harbor mutations involving the interleukin-6 signal transducer), and (4) unclassified. I-HCAs and H-HCAs account for the majority (80%), while b-HCAs comprise about 10%–15% [2]. Ten percent of I-HCAs also demonstrate β-catenin mutation; however, H-HCAs and b-HCAs are mutually exclusive [3]. HCAs appear as unencapsulated tumors that may be solitary or multiple. Adenomatosis, a term used when greater than 10 adenomas are encountered, can be associated with maturity onset diabetes of the young type 3 (MODY3). Histologically, HCAs are characterized by plates of hepatocytes that lack portal tract elements and are separated by sinusoids. Immunohistochemical staining techniques proposed by the Bordeaux group [1] and validated by others [4–6] aid in the classification of HCAs into the different subtypes which are reviewed briefly in the following. H-HCAs result from inactivating mutations in the hepatocyte nuclear factor 1 A (HNF1A) gene.
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