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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Apolipoprotein E polymorphism influences orthotopic liver transplantation outcomes in patients with hepatitis C virus-induced liver cirrhosis
José Carlos Rodrigues Nascimento, Lianna C Pereira, Juliana Magalhães C Rêgo, Ronaldo P Dias, Paulo Goberlânio B Silva, Silvio Alencar C Sobrinho, Gustavo R Coelho, Ivelise Regina C Brasil, Edmilson F Oliveira-Filho, James S Owen, Pierluigi Toniutto, Reinaldo B Oriá
José Carlos Rodrigues Nascimento, Department of Anesthesia and Surgery Liver Transplantation, Fortaleza General Hospital, Fortaleza 60150-160, CE, Brazil
José Carlos Rodrigues Nascimento, Lianna C Pereira, Juliana Magalhães C Rêgo, Ronaldo P Dias, Silvio Alencar C Sobrinho, Reinaldo B Oriá, Laboratory of the Biology of Tissue Healing, Ontogeny and Nutrition, Department of Morphology and Institute of Biomedicine, School of Medicine, Federal University of Ceará, Fortaleza 60430-270, CE, Brazil
Paulo Goberlânio B Silva, Department of Dental Clinic, Federal University of Ceará, Fortaleza 60430-270, CE, Brazil
Gustavo R Coelho, Department of Surgery, Liver Transplant Unit of Federal University of Ceará, Fortaleza 60430-270, CE, Brazil
Ivelise Regina C Brasil, Transplantation Division, Hospital Geral de Fortaleza, Fortaleza 60175-742, CE, Brazil
Edmilson F Oliveira-Filho, Institute of Virology, Charité Universitätsmedizin Berlin, Berlin 10117, Germany
James S Owen, UCL Medical School, Royal Free Campus, London NW3 2PF, United Kingdom
Pierluigi Toniutto, Department of Specialized Medicine, Hepatology Liver Transplantation Unit, Azienda Sanitaria Universitaria Integrata of Udine, Udine I-33100, Italy
Author contributions: Nascimento JCR, Pereira LC, Rêgo JMC, Dias RP, Silva PGB, Sobrinho SAC, Coelho GR, Brasil IRC, Owen JS, Toniutto P, and Oriá RB contributed to the study design; Nascimento JCR and Pereira LC were involved in data collection; Nascimento JCR, Silva PGB, Coelho GR, Brasil IRC, Owen JS, Toniutto P, and Oriá RB were involved in data analysis and interpretation of data; Nascimento JCR, Coelho GR, Brasil IRC, Oliveira-Filho EF, Owen JS, Toniutto P, and Oriá RB contributed to writing of the manuscript and in critical revision of the manuscript for important intellectual content; and Oriá RB supervised the study.
Supported by the National Council for Scientific and Technological Development, No. CNPq; the Coordination for the Improvement of Higher Education Personnel, No. CAPES; and the Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico, No. FUNCAP.
Institutional review board statement: All study procedures were in accordance and with the 1964 Helsinki declaration and the study protocol was approved by the Research Ethics Committee of the Federal University of Ceará, protocol No. 2.018.768.
Informed consent statement: All patients were approached by the research team, who explained the study protocol and clarified that failure to participate in the study would not cause discontinuation of care or medical treatment. After that, patients read and signed the informed consent form.
Conflict-of-interest statement: The authors have no conflicts of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE statement, and the manuscript was prepared and revised accordingly.
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:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Reinaldo B Oriá, DVM, PhD, Associate Professor, Research Scientist, Laboratory of the Biology of Tissue Healing, Ontogeny and Nutrition, Department of Morphology and Institute of Biomedicine, School of Medicine, Federal University of Ceará, Nunes de Melo, 1315–Rodolfo Teófilo, Fortaleza 60430-270, CE, Brazil. oria@ufc.br
Received: December 24, 2020
Peer-review started: December 24, 2020
First decision: January 10, 2021
Revised: January 21, 2021
Accepted: March 1, 2021
Article in press: March 1, 2021
Published online: March 21, 2021
BACKGROUND
Hepatitis C virus (HCV) infection is responsible for a chronic liver inflammation, which may cause end-stage liver disease and hepatocellular carcinoma. Apolipoprotein E (protein: ApoE, gene: APOE), a key player in cholesterol metabolism, is mainly synthesized in the liver and APOE polymorphisms may influence HCV-induced liver damage.
AIM
To determine whether APOE alleles affect outcomes in HCV-infected patients with liver cirrhosis following orthotopic liver transplantation (OLT).
METHODS
This was a cohort study in which 179 patients, both genders and aged 34-70 years, were included before or after (up to 10 years follow-up) OLT. Liver injury severity was assessed using different criteria, including METAVIR and models for end-stage liver disease. APOE polymorphisms were analyzed by quantitative real-time polymerase chain reaction.
RESULTS
The APOE3 allele was the most common (67.3%). In inflammation severity of biopsies from 89 OLT explants and 2 patients in pre-transplant, the degree of severe inflammation (A3F4, 0.0%) was significantly less frequent than in patients with minimal and moderate degree of inflammation (≤ A2F4, 16.2%) P = 0.048, in patients carrying the APOE4 allele when compared to non-APOE4. In addition, a significant difference was also found (≤ A2F4, 64.4% vs A3F4, 0.0%; P = 0.043) and (A1F4, 57.4% vs A3F4, 0.0%; P = 0.024) in APOE4 patients when compared to APOE3 carriers. The fibrosis degree of the liver graft in 8 of 91 patients and the lack of the E4 allele was associated with more moderate fibrosis (F2) (P = 0.006).
CONCLUSION
Our results suggest that the E4 allele protects against progression of liver fibrosis and degree of inflammation in HCV-infected patients.
Core Tip: Hepatitis C virus (HCV) infection is responsible for a chronic liver inflammation, which may cause end-stage liver disease. Apolipoprotein E (protein: ApoE, gene: APOE) is key for lipid metabolism. In this study, the APOE4 allele, which has been associated with increased risk of acquiring late-onset Alzheimer’s disease, was found to have a protective effect against the progression of inflammation and/or fibrosis in liver damage induced by HCV pre- and post-liver transplantation. Further studies are needed to unravel the possible contribution of ApoE from the donor liver to this protection.
