Observational Study
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World J Gastroenterol. Jul 14, 2014; 20(26): 8667-8673
Published online Jul 14, 2014. doi: 10.3748/wjg.v20.i26.8667
Pro-atherosclerotic markers and cardiovascular risk factors one year after liver transplantation
Mario Reis Alvares-da-Silva, Claudia Pinto Marques Souza de Oliveira, José Tadeu Stefano, Hermes V Barbeiro, Denise Barbeiro, Francisco G Soriano, Alberto Queiroz Farias, Flair José Carrilho, Luiz Augusto Carneiro D’Albuquerque
Mario Reis Alvares-da-Silva, Luiz Augusto Carneiro D’Albuquerque, Division of Liver and Gastrointestinal Transplant (LIM-37), Department of Gastroenterology, University of São Paulo School of Medicine, 05508-070 São Paulo, Brazil
Mario Reis Alvares-da-Silva, Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcellos, 90035-903 Porto Alegre, Brazil
Claudia Pinto Marques Souza de Oliveira, José Tadeu Stefano, Alberto Queiroz Farias, Flair José Carrilho, Division of Clinical (LIM-07), Department of Gastroenterology, University of São Paulo School of Medicine, 05508-070 São Paulo, Brazil
Hermes V Barbeiro, Denise Barbeiro, Francisco G Soriano, Division of Emergency Medicine (LIM-51), University of São Paulo School of Medicine, 05508-070 São Paulo, Brazil
Author contributions: Alvares-da-Silva MR and Oliveira CPMS designed the study, collected the data and performed and co-wrote the manuscript; Stefano JT provided and coordinated the collection of all the human materials; Barbeiro HV, Barbeiro D and Soriano FG performed most of the laboratory analyses; Farias AQ coordinated the collection of all the human materials; Carrilho FJ and Carneiro D’Albuquerque LA co-designed the study, and provided financial support for this work; all co-authors reviewed and approved the final manuscript.
Supported by Department of Gastroenterology LIM-37/LIM07, School of Medicine, University of São Paulo, Brazil
Correspondence to: Mario Reis Alvares-da-Silva, MD, PhD, Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcellos, 2350, sala 2033, 90035-903 Porto Alegre, Brazil. marioreis@live.com
Telephone: +55-51-33598307 Fax: +55-51-33598307
Received: January 30, 2014
Revised: March 18, 2014
Accepted: April 15, 2014
Published online: July 14, 2014
Abstract

AIM: To investigate pro-atherosclerotic markers (endothelial dysfunction and inflammation) in patients one year after liver transplantation.

METHODS: Forty-four consecutive liver transplant (LT) outpatients who were admitted between August 2009 and July 2010, were followed-up by for 1 year, exhibited no evidences of infection or rejection, all of them underwent tacrolimus-based immunosuppressive regimens were consecutively enrolled. Inflammatory cytokines (TNFα, IFNγ, IL-8, and IL-10), endothelial biomarkers (sVCAM-1, sICAM-1, MPO, adiponectin, PAI-1, SAP, SAA, E-selectin, and MMP-9), high sensitive C-reactive protein, and Framingham risk score (FRS) were assessed. The anthropometric data, aminotransferases, metabolic syndrome features, glucose and lipid profiles, and insulin resistance data were also collected. The LT recipients were compared to 22 biopsy-proven non-alcoholic steatohepatitis (NASH) patients and 20 healthy controls (non-obese, non-diabetics, and non-dyslipidemic).

RESULTS: The LT recipients had significantly younger ages and lower body mass indices, aminotransferases, fasting glucose and insulin levels, glucose homeostasis model and metabolic syndrome features than the NASH patients. Classic cardiovascular risk markers, such as Hs-CRP and FRS [2.0 (1.0-8.75)], were lower in the LT patients compared to those observed in the NASH patients (P = 0.009). In contrast, the LT recipients and NASH patients had similar inflammatory and endothelial serum markers compared to the controls (pg/mL): lower IL-10 levels (32.3 and 32.3 vs 62.5, respectively, P = 0.019) and higher IFNγ (626.1 and 411.9 vs 67.9, respectively, P < 0.001), E-selectin (48.5 and 90.03 vs 35.7, respectively, P < 0.001), sVCAM-1 (1820.6 and 1692.4 vs 1167.2, respectively, P < 0.001), and sICAM-1 (230.3 and 259.7 vs 152.9, respectively, P = 0.015) levels.

CONCLUSION: Non-obese LT recipients have similar pro-atherosclerotic serum profiles after a short 1-year follow-up period compared to NASH patients, suggesting a high risk of atherosclerosis in this population.

Keywords: Cell adhesion molecules, Endothelial biomarkers, Cardiovascular disease, Nonalcoholic steatohepatitis, Metabolic syndrome

Core tip: Liver transplant (LT) patients a have high risk of long-term development of cardiovascular disease (CVD), which is currently recognized as an important cause of death 5 to 10 years after transplant in this population. Atherosclerosis is a hallmark of CVD, with both disorders involving a prolonged asymptomatic phase and often leading to morbidity and mortality upon initial clinical presentation. Regardless, endothelial dysfunction is the first step in developing early atherosclerosis. In the present study, we evaluated inflammatory and endothelial markers one year after transplantation in asymptomatic LT recipients in comparison to high-CVD-risk biopsy-proven nonalcoholic steatohepatitis (NASH) patients and healthy controls. We found that LT recipients had pro-inflammatory profiles and endothelial dysfunction similar to those of NASH patients, both of which were higher than those in the compared controls. These findings suggest that LT recipients, even in a short 1-year follow-up period, display a high atherosclerotic risk and should be carefully monitored to effectively prevent CVD.