Hepatic Adenomatosis: A Systematic Review of Definitions, Management, and Outcomes in Published Cases

Introduction: Hepatic adenomatosis (HA), the multifocal phenotype of hepatocellular adenoma, is variably defined and managed. Methods: We performed a PRISMA-guided systematic review of MEDLINE, Embase, Web of Science, and CINAHL from inception through August 25, 2025, and included human case reports or case series with original clinical data. Results: The review included 54 reports describing 55 patients. Most patients were female (81.8%), with median age of 34 years (IQR 26–48). A ≥10-lesion threshold was used in 68.5% of definitions. When lesion burden was quantifiable, the median lesion count was 15 (IQR 10–30; range 4–200). The median largest-lesion diameter was 80 mm (IQR 50–100; maximum 170 mm), and 80.4% measured ≥5 cm. Magnetic resonance imaging (MRI) was reported in two-thirds of cases, whereas hepatobiliary-phase imaging and molecular subtyping were rarely described. Management included observation, resection, embolization, ablation, and transplantation, most often for size, hemorrhage risk, or malignancy concern; reported follow-up documented hemorrhage and malignant transformation in approximately 10% each, likely reflecting publication and severity bias. Discussion/Conclusion: This synthesis supports a pragmatic approach centered on a standardized operational definition, hepatobiliary-contrast MRI, selective targeted biopsy/molecular profiling of index lesions, withdrawal of exogenous hormones, and risk-adapted intervention for high-risk disease.