The effect of oral contraceptive pill cessation on hepatocellular adenoma diameter: A retrospective cohort study

Abstract

Background & Aims Hepatocellular adenomas (HCA) are rare, hormone‐driven, benign liver tumours. HCA >50 mm are associated with haemorrhage and malignant transformation. Guidelines recommend cessation of oral contraceptive pills (OCP) for size reduction; however, it is currently unknown how HCA respond to cessation of OCP. We sought to investigate the effect of OCP cessation on HCA size. Methods A retrospective cohort study was performed including HCA patients who stopped OCP intake within 6 months of imaging between 2005 and 2018. Biometrics and hormonal medication use were evaluated with self‐designed questionnaires. Response of the largest HCA was evaluated according to Response Evaluation Criteria in Solid Tumours (RECISTv1.1). Cox regression was performed for analysis of factors influencing HCA regression. Results Seventy‐eight HCA patients were included, diagnosed at a median (interquartile range) age of 32 (26‐41) years. Follow‐up was 1.6 (0.4‐2.9) years. HCA size at diagnosis ranged 10‐167 mm. After a median time of 1.3 (0.6‐2.6) years after OCP cessation, 37.2% of HCA showed ≥30% regression, 5.1% complete regression, 56.4% stability and 1.3% progression. No HCA‐induced complications were observed during follow‐up. Cox regression analysis demonstrated a significant association of HCA size with rate of regression; 50 ≤ HCA < 100 mm (HR 2.4, 95% CI 1.1‐5.3; P < 0.05), HCA ≥ 100 mm (HR 8.3, 95% CI 3.3‐21.6; P < 0.001). Conclusions Ninety‐eight per cent of HCA remained stable or regressed after OCP cessation. A longer wait‐and‐see period was associated with a larger proportion of regressing HCA, without HCA‐related complications during follow‐up.

Multiple hepatocellular adenomas associated with long-term administration of androgenic steroids for aplastic anemia

“…[ 26 ] In case of AAS-induced HA, discontinuation of AAS may regress the mass and thereby potentially prevent unnecessary hepatic surgery. Martijn et al [ 27 ] stated that 98% of HAs follow this trend, and a conservative approach could lead to HA regression below 50 mm. Moreover, a study of 180 patients diagnosed with HA >5 cm found that 81 patients (45%) treated with conservative therapy reached the clinical regression endpoint of <5 cm after a median of 34 months.…”

Challenging Issues in Hepatic Adenoma

“…Even more so, patients with metabolic syndrome and hepatic adenomas seem to be associated with a higher rate of malignization [8]. The association between oral contraceptive use and metabolic syndrome on one hand and HA on the other tends to prove an important hormonal sensitivity of the tumor (obesity is associated with higher estrogen levels), and this is supported by the fact that adenomas may stop their evolution or even regress as a result of oral contraceptive cessation [15]. In spite of this, immunohistological studies failed to prove the direct effect of these hormones via steroid receptors in normal and adenomatous hepatic tissue, and so the mechanism by which high estrogen levels may cause an adenomatous transformation is still incompletely understood [16].…”

“…Apart from estrogen, use of anabolic androgens has also been linked to a higher incidence in HAs, which is being proved not only in body builders but also in patients treated with steroids for Fanconi syndrome, aplastic anemia, etc. Cessation of steroid use has also been linked to regression in size of HAs [15].…”

“…Hepatic adenoma in GSD occurs before the age of 20 years, is more common in males, and is typically multiple. Dietary therapy and correction of insulin, glucose, and glucagon levels have been proved to lead to regression of adenomas [15]. The mechanism by which GSD is involved in the development of HA is also unknown.…”

Radiological aspects of giant hepatocellular adenoma of the left liver: A case report

“…Congenital HCA is more common in infants and may stem from the unconnected isolated embryonic hepatocytes. Acquired HCA occurs mostly in young women with a history of oral contraceptive use, with an estimated incidence of 3-4 per 100000 women[1,2]. This may be due to the fact that oral contraceptives promote necrosis of hepatocytes and regeneration of nodules, leading to the development of HCA.…”