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.

Keywords: hepatocellular adenoma; oral contraceptive pill; regression; treatment algorithm.

Figure 1

Flowchart of included patients. Abbreviations: HCA, hepatocellular adenoma; GSD, glycogen storage disease; HNF1A‐MODY, hepatocyte nuclear factor 1a inactivated maturity onset diabetes of the young; OCP, oral contraceptive pill.

Figure 2

Spider plot of the relative change of largest HCA diameter from baseline over time for all evaluable patients (n = 78), defined as those with baseline tumour assessments and at least one postbaseline assessment. Lines are colour coded based on overall response. Horizontal dashed lines represent Response Evaluation Criteria In Solid Tumours version 1.1 guideline for partial response (≥30% decrease in target lesion) and progressive disease (≥20% increase in target lesion). Abbreviations: HCA, hepatocellular adenoma; OCP, oral contraceptive pill. Legend: Blue, HCA diameter <50 mm; Orange, HCA diameter >50 mm; Green, HCA diameter >50 mm at baseline, regression to <50 mm size; Red triangle, surgical intervention; Red circle, percutaneous intervention

Figure 3

(A‐D) Kaplan‐Meier curves for the percentage of HCA showing 30% or more regression. (A) All HCA, (B) subdivided by initial HCA diameter, (C) duration of OCP use (*22 missing cases) and (D) BMI (*7 missing cases). HCA, hepatocellular adenoma; OCP, oral contraceptive pill; BMI, body mass index