Retrospective Cohort Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 27, 2018; 10(1): 41-50
Published online Jan 27, 2018. doi: 10.4254/wjh.v10.i1.41
Fatty liver disease, an emerging etiology of hepatocellular carcinoma in Argentina
Federico Piñero, Josefina Pages, Sebastián Marciano, Nora Fernández, Jorge Silva, Margarita Anders, Alina Zerega, Ezequiel Ridruejo, Beatriz Ameigeiras, Claudia D’Amico, Luis Gaite, Carla Bermúdez, Manuel Cobos, Carlos Rosales, Gustavo Romero, Lucas McCormack, Virginia Reggiardo, Luis Colombato, Adrián Gadano, Marcelo Silva
Federico Piñero, Josefina Pages, Marcelo Silva, Hepatology and Liver Transplantation Unit, Hospital Universitario Austral, Buenos Aires 1629, Argentina
Federico Piñero, Sanatorio Trinidad San Isidro, Buenos Aires 1642, Argentina
Federico Piñero, Clínica Privada San Fernando, Buenos Aires 2013, Argentina
Sebastián Marciano, Carla Bermúdez, Adrián Gadano, Hepatology Section, Liver Transplant Program, Department of Academic Research, Hospital Italiano from Buenos Aires, Buenos Aires 1424, Argentina
Nora Fernández, Luis Colombato, Hepatology and Gastroenterology, Hospital Británico, Buenos Aires 1280, Argentina
Jorge Silva, Carlos Rosales, Hepatobiliary Surgery, Hospital G Rawson, San Juan 5400, Argentina
Margarita Anders, Manuel Cobos, Lucas McCormack, Department of Hepatology and Liver Transplant Program, Hospital Aleman, Buenos Aires 1118, Argentina
Alina Zerega, Department of Hepatology and Liver Transplantation, Sanatorio Allende, Córdoba 5016, Argentina
Ezequiel Ridruejo, Hepatology Section, Department of Medicine, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno “CEMIC”, Buenos Aires 1425, Argentina
Beatriz Ameigeiras, Department of Hepatology, Hospital Ramos Mejía, Buenos Aires 1221, Argentina
Claudia D’Amico, Department of Hepatology, Centro Especialidades Medicas Ambulatorias (CEMA), Mar del Plata 7600, Argentina
Luis Gaite, Department of Hepatology and Liver Transplantation, Clínica de Nefrología de Santa Fe, Santa Fe 3000, Argentina
Gustavo Romero, Department of Hepatology and Gastroenterology, Hospital C Bonorino Udaondo, Buenos Aires 1264, Argentina
Virginia Reggiardo, Department of Hepatology and Gastroenterology, Hospital Centenario, Santa Fe 2002, Argentina
Author contributions: Piñero F, Pages J, Ridruejo E, Colombato L and Silva M, participated in concept and design, statistical analysis and writing of article; Piñero F participated in statistical analysis; all other authors participated in data recording and critical review of the manuscript.
Institutional review board statement: The study was reviewed and approved by the Austral University, School of Medicine and the Bioethics Institutional Committee of the Austral University Hospital (CIE approval study protocol number 14-039).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to the study enrollment. We submit the informed consent (IC) and the Spanish version approved by the Austral University, School of Medicine and the Bioethics Institutional Committee of the Austral University Hospital (CIE approval study protocol number 14-039).
Conflict-of-interest statement: The authors of this manuscript have no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: 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:
Correspondence to: Dr. Federico Piñero, MD, Academic Research, Research Scientist, Staff Physician, Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Av. Presidente Perón 1500, Buenos Aires 1264, Argentina.
Telephone: +54-230-4482000 Fax: +54-230-4482236
Received: October 31, 2017
Peer-review started: November 1, 2017
First decision: December 1, 2017
Revised: December 7, 2017
Accepted: January 15, 2018
Article in press: January 15, 2018
Published online: January 27, 2018

To investigate any changing trends in the etiologies of hepatocellular carcinoma (HCC) in Argentina during the last years.


A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease (NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical visit.


A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers (n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC (37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLD-HCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015 (4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3% (P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups (6.6 ng/mL vs 26 ng/mL; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher mortality.


The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.

Keywords: Hepatocellular carcinoma, Etiology, Fatty liver, South America

Core tip: Despite the increasing incidence of non-alcoholic fatty liver disease (NAFLD) and NAFLD related hepatocellular carcinoma (HCC) in developed countries, information related with the burden of NAFLD-HCC in developing countries as those in South America is lacking. In this multicenter cohort study from Argentina including patients with HCC, while HCV and alcoholic related cirrhosis were the most frequent causes of HCC between 2009 and 2016, NAFLD-HCC had a 6-fold increased during the same period. This changing scenario was observed without precluding any specific etiology of liver disease. NAFLD might become one of the first HCC related causes in the coming decades; an issue to be consider with effective prevention strategies.