Sato-Espinoza K, Valdivia-Herrera M, Chotiprasidhi P, Diaz-Ferrer J. Hepatocellular carcinoma in patients without cirrhosis. World J Gastroenterol 2025; 31(23): 107100 [DOI: 10.3748/wjg.v31.i23.107100]
Corresponding Author of This Article
Javier Diaz-Ferrer, MD, Associate Professor, Hepatology Service, Department of Digestive Diseases, Hospital Nacional Edgardo Rebagliati Martins, 490 Edgardo Rebagliati Avenue, Lima 15072, Peru. jodf13@hotmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Jun 21, 2025; 31(23): 107100 Published online Jun 21, 2025. doi: 10.3748/wjg.v31.i23.107100
Hepatocellular carcinoma in patients without cirrhosis
Karina Sato-Espinoza, Mayra Valdivia-Herrera, Perapa Chotiprasidhi, Javier Diaz-Ferrer
Karina Sato-Espinoza, Perapa Chotiprasidhi, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN 55902, United States
Mayra Valdivia-Herrera, Escuela de Medicina Humana, Facultad de Ciencias de la Salud, Universidad Cientifica del Sur, Lima 15067, Peru
Javier Diaz-Ferrer, Hepatology Service, Department of Digestive Diseases, Hospital Nacional Edgardo Rebagliati Martins, Lima 15072, Peru
Javier Diaz-Ferrer, Department of Gastroenterology Service, Clinica Internacional, Lima 15036, Peru
Javier Diaz-Ferrer, Medicine Faculty, Universidad San Martin de Porres, Lima 15024, Peru
Author contributions: Sato-Espinoza K, Valdivia-Herrera M, Chotiprasidhi P, and Diaz-Ferrer J performed the methodology and wrote, reviewed, and edited the manuscript.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Javier Diaz-Ferrer, MD, Associate Professor, Hepatology Service, Department of Digestive Diseases, Hospital Nacional Edgardo Rebagliati Martins, 490 Edgardo Rebagliati Avenue, Lima 15072, Peru. jodf13@hotmail.com
Received: March 16, 2025 Revised: April 22, 2025 Accepted: May 27, 2025 Published online: June 21, 2025 Processing time: 97 Days and 14.7 Hours
Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, the sixth most common cancer worldwide, and the third leading cause of cancer-related death. Cirrhosis is the predominant risk factor for HCC, driven by major etiologies including hepatitis B and C, excessive alcohol consumption, and metabolic dysfunction-associated steatotic liver disease (MASLD). While approximately 80% of HCC cases occur in patients with cirrhosis, its incidence among individuals without cirrhosis has significantly increased, particularly in developed countries, driven by the rising prevalence of MASLD. The prevalence of patients with non-cirrhotic HCC varies geographically, yet data on this subgroup remain limited. Consequently, screening and clinical management guidelines for patients with non-cirrhotic HCC are underdeveloped. Current surveillance is typically not recommended for non-cirrhotic populations, except for individuals with hepatitis B, and diagnostic criteria like Liver Imaging Reporting and Data System are designed explicitly for cirrhotic or hepatitis B-associated HCC. Furthermore, treatment strategies for non-cirrhotic HCC are often extrapolated from studies focused on patients with cirrhosis, leading to gaps in knowledge regarding treatment efficacy, survival outcomes, and etiological variability in non-cirrhotic cohorts. Thus, emerging evidence must be reviewed to guide the development of enhanced diagnostic and therapeutic strategies for patients with non-cirrhotic HCC. To address these gaps, we comprehensively reviewed the epidemiology, clinical and genetic characteristics, diagnostic modalities, and therapeutic approaches for patients with non-cirrhotic HCC.
Core Tip: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and the incidence of HCC among individuals without cirrhosis is on the rise, correlating with increasing rates of obesity and metabolic syndrome. Targeted surveillance is advised for high-risk groups, especially those with chronic hepatitis B infection, while it remains unrecommended for individuals with metabolic dysfunction-associated steatotic liver disease. Liver biopsy is the only diagnostic method available for this population, highlighting the need for further non-invasive diagnostic tools. This review summarizes the epidemiology, clinical and genetic characteristics, diagnostic methods, and treatment options for patients with non-cirrhotic HCC.
