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Adrenal metastasis of hepatocellular carcinoma after liver transplantation: Case report and systematic review of literature
José Manuel Ramia, Mariano Franco, Cándido Alcázar, Silvia Carbonell-Morote, Juan Jesús Rubio-García, María Rodríguez, Sonia Pascual, Paola Melgar, Celia Villodre Tudela
José Manuel Ramia, Mariano Franco, Cándido Alcázar, Silvia Carbonell-Morote, Juan Jesús Rubio-García, María Rodríguez, Sonia Pascual, Paola Melgar, Celia Villodre Tudela, ISABIAL, Alicante 03010, Valencia, Spain
José Manuel Ramia, Cándido Alcázar, Silvia Carbonell-Morote, Celia Villodre Tudela, Surgery, Universidad Miguel Hernández, Elche 03202, Valencia, Spain
José Manuel Ramia, Mariano Franco, Cándido Alcázar, Silvia Carbonell-Morote, Juan Jesús Rubio-García, Paola Melgar, Celia Villodre Tudela, Department of Surgery, Hospital General Universitario Dr. Balmis, Alicante 03010, Valencia, Spain
María Rodríguez, Sonia Pascual, Hepatology Unit, Department of Gastroenterology, Hospital General Unversitario Dr. Balmis, Alicante 03010, Valencia, Spain
Co-corresponding authors: José Manuel Ramia and Juan Jesús Rubio-García.
Author contributions: Ramia JM conceptualization, data curation, investigation, methodology, project administration, supervision, visualization, writing-original draft and writing-review and editing; Franco M conceptualization, investigation, methodology and writing-review and editing; Alcázar C data curation, investigation, and writing-review and editing; Carbonell-Morote S conceptualization, investigation, methodology, software provider, and writing-review and editing; Rubio-García JJ conceptualization, data curation, investigation, funding acquision, project administration, writing-original draft and writing-review and editing; Rodriguez M conceptualization, investigation, methodology, and writing-review and editing; Pascual S conceptualization, investigation, methodology, and writing-review and editing; Melgar P conceptualization, investigation, validation, and writing-review and editing; Tudela CV conceptualization, investigation, software provider, supervision, validation, and writing-review and editing. The designation of two co-authors reflects the essential contributions made by both individuals to the study’s design, the drafting and critical revision of the text, and the careful adaptation of the submission to the journal’s standards and formal requirements, the oversight of the peer-review process, and the implementation of the requested revisions in full. Given this shared responsibility and sustained engagement at every stage of the submission and revision process, we consider it appropriate to formally identify both researchers as corresponding authors. This designation ensures that the responsibilities and academic contributions of both authors are accurately and transparently represented.
Supported by The Instituto de Investigación Sanitaria y Biomédica de Alicante.
Conflict-of-interest statement: Not applicable because of no competing interests.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: José Manuel Ramia, MD, PhD, FACS, FRCS, Department of Surgery, Hospital General Universitario Dr. Balmis, Alicante 03010, Valencia, Spain.
jose_ramia@hotmail.com
Received: November 26, 2025
Revised: January 10, 2026
Accepted: March 5, 2026
Published online: June 18, 2026
Processing time: 184 Days and 22.3 Hours
BACKGROUND
Adrenal metastasis of hepatocellular carcinoma (AM-HCC) after liver transplantation (LT) is an infrequent entity, especially when it is the only site of recurrence. We present patients with these characteristics and systematically review previously published cases. No systematic review adhering to PRISMA criteria has been previously performed.
AIM
To systematic review of isolated AM-HCC after LT.
METHODS
Adhering to PRISMA guidelines, we performed unrestricted search for AM-HCC after LT in several databases, with no language restriction, updated through December 31, 2024.
RESULTS
We obtained 38 articles. Only 14 articles, comprising 20 patients, were evaluated, to which we added our own case. Fourteen were single-case reports, and one was a series of seven retrospective cases. The median age was 56.1 years [interquartile range (IQR): 23-72]. The gender distribution was predominantly male (84.6%). The indications for LT were hepatocellular carcinoma (HCC) plus hepatitis B virus cirrhosis (11), hepatitis C virus (6), alcohol (3), and cryptogenic cirrhosis (1). The median HCC tumor size was 4.6 cm (IQR: 3.8-13). One third of patients did not meet the Milan criteria. The median time between LT and the appearance of adrenal metastasis (AM) was 39.9 months (IQR: 18-42.6). The AM was located on the left (11) and right side (10). Nineteen patients were treated with adrenalectomy, and two were treated with radiotherapy. After a median follow-up of 30 months, 25% of patients were alive without recurrence. The median survival time was 29 months (IQR: 24-38).
CONCLUSION
In the case of AM-HCC after LT, occurring as the solitary site of extrahepatic metastasis, adrenalectomy could be a therapeutic option for surgical candidates. It is safe, appears to increase survival, and reduces recurrence in selected patients.
Core Tip: We present a systematic review of isolated adrenal metastasis of hepatocellular carcinoma after liver transplantation, including a patient who was treated at our center. Previous manuscripts on this topic have not included a PRISMA-based systematic review; therefore, this is the first systematic review conducted. Our findings clearly demonstrate that there is currently a lack of consensus on how to treat these patients, indicating the need for an international consensus.
