What causes hepatocellular adenoma (HCA)?

Updated: Feb 21, 2018
  • Author: Bradford A Whitmer, DO; Chief Editor: BS Anand, MD  more...
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Causes of hepatocellular adenoma include oral contraceptive medications containing mestranol as well as anabolic steroids. Thus, hepatocellular adenomas occur mostly in women of childbearing age and are strongly associated with the use of oral contraceptive pills (OCPs) and other estrogens. This is reflected by a dramatic increase in the incidence of this disease since OCPs were introduced in the 1960s. For example, before the use of OCPs, no hepatic adenomas were reported at surgery at the Mayo Clinic between 1907 and 1954. Edmonson reported finding only 2 adenomas among 50,000 autopsy specimens at Los Angeles County Hospital between 1907 and 1958. [1] However, in women using OCPs, adenomas were more common in patients taking OCPs containing higher doses of estrogen and with prolonged use (73.4 mo) when compared with matched controls (36.2 mo) (P< 0.001). [2]

In a case series of 3 patients, Baum et al also suggested an association between hepatic adenomas and OCPs. [3] Klatskin [4] and Rooks et al [5] reported that the greatest risk occurs in women older than age 30 years taking OCPs for longer than 5 years, but in 10% of patients, exposure may be as short as 6-12 months. Cherqui et al also reported that adenomas are occasionally diagnosed after discontinuation of OCPs. [6]

Decreases in dosages and the types of hormones contained in OCPs have led to a reduction in adenoma incidence, as reported by another study by Edmonson et al. [7] Rooks et al reported that in women who have never used OCPs, the annual incidence of hepatic adenoma is 1 to 1.3 per million but increases to 3.4 per 100,000 in long-term users. [5] Currently, benign liver tumors may be detected more frequently though, owing to increased routine use of medical imaging.

Hepatic adenomas may be single or multiple, and they may occasionally reach a size larger than 20 cm. In addition to OCPs, other conditions associated with adenomas are anabolic steroids, androgenic steroids, beta-thalassemia, tyrosinemia, type 1 diabetes mellitus, hemochromatosis, barbiturate usage, clomiphene intake, and glycogen storage diseases (GSDs) (types 1 and 3). However, multiple hepatic adenomas are more common in glycogen storage disease, with an incidence between 22% and 75% in type 1 and 25% in type 3 disease. [8]

In addition to a multiplicity of adenomas, hepatic adenomas associated with GSD tend to occur more commonly in men than women (ratio 2:1) and often develop before the age of 20 years. [9, 10] This should not be confused with hepatic adenomatosis, which is an equally uncommon condition in which at least 10 lesions develop at equal frequency in either sex in the absence of the classic risk factors such as OCP or GSD. [11]

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