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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
ARTICLE HIGHLIGHTS
Research background
Hepatitis C virus (HCV) can cause chronic liver inflammation, end-stage liver disease and hepatocellular carcinoma (HCC). Apolipoprotein E (protein: ApoE, gene: APOE) is mainly liver synthesized and APOE polymorphisms may affect HCV-induced liver damage after orthotopic liver transplantation (OLT).
Research motivation
Although APOE4 may protect against HCV-induced liver damage, the role of APOE genotypes in modifying HCV-induced liver injury in post-OLT has not been reported.
Research objectives
To establish if APOE4 genotype OLT recipients have more benign HCV-related liver injuries compared to patients with APOE2 or APOE4 genotypes.
Research methods
Patients with HCV-related end-stage liver disease, 105 of 179 complicated with HCC, were assessed pre-OLT (179) and post-OLT (144; with a 1-year follow-up for 132 patients). Liver injury analyses included METAVIR and models for end-stage liver disease scores, while APOE genotype was determined by qRT-PCR.
Research results
HCV positive recipients with severe hepatic inflammation had low APOE4 genotype frequency, compared to those with minimal and moderate inflammation. In addition, liver fibrosis was lower in patients carrying APOE4 genotype compared to those carrying the most common APOE3 genotype.
Research conclusions
We found that carriage of APOE4 genotype protects pre-OLT patients against HCV-induced severe hepatic inflammation, and against fibrosis progression post-OLT.
Research perspectives
We propose that carriage of APOE4 genotype protects against progression of inflammation and liver fibrosis in recurrent HCV hepatitis after OLT, but additional studies are needed to assess whether donor-derived ApoE4 protein directly affects these processes.
