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©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
Serum proinflammatory cytokines and nutritional status in pediatric chronic liver disease
Daniele Santetti, Maria Inês de Albuquerque Wilasco, Cristina Toscani Leal Dornelles, Isabel Cristina Ribas Werlang, Fernanda Urruth Fontella, Carlos Oscar Kieling, Jorge Luiz dos Santos, Sandra Maria Gonçalves Vieira, Helena Ayako Sueno Goldani
Daniele Santetti, Maria Inês de Albuquerque Wilasco, Post-Graduate Program of Child and Adolescent Health, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90035-903, Brazil
Cristina Toscani Leal Dornelles, Nutrition Service, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90035-903, Brazil
Isabel Cristina Ribas Werlang, Fernanda Urruth Fontella, Laboratory of Translational Pediatrics-NESCA, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90035-903, Brazil
Carlos Oscar Kieling, Jorge Luiz dos Santos, Sandra Maria Gonçalves Vieira, Pediatric Hepatology Unit, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90035-903, Brazil
Helena Ayako Sueno Goldani, Pediatric Gastroenterology Unit, Hospital de Clínicas de Porto Alegre and Post-Graduate Program of Child and Adolescent Health, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul 90035-903, Brazil
Author contributions: Santetti D, Dornelles CTL and Goldani HAS designed the study, analyzed the data and wrote the manuscript; Santetti D collected the data; de Albuquerque Wilasco MI was involved in editing the manuscript; Fontella FU and Werlang ICR performed the laboratory assays; Kieling CO, dos Santos JL and Vieira SMG analyzed the data and edited the manuscript.
Supported by Fundo de Incentivo a Pesquisa (FIPE), Hospital de Clinicas de Porto Alegre, Post-Graduate Program of Child and Adolescent Health-UFRGS and Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq), Brazil.
Institutional review board statement: This study was reviewed and approved by the Research and Ethics Committee of Hospital de Clinicas de Porto Alegre (protocol no.11/0078).
Clinical trial registration: The authors of the manuscript entitled “Serum proinflammatory cytokines and nutritional status in pediatric chronic liver disease” declare that this study is registered at the Research and Ethics Committee of Hospital de Clinicas de Porto Alegre, Brazil (IRB00000921). The registration identification number is 11-0078.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they 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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Daniele Santetti, MSc, Post-Graduate Program of Child and Adolescent Health, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rua Ramiro Barcelos, 2350 Porto Alegre, Rio Grande do Sul 90035-903, Brazil.
danisantetti@gmail.com
Telephone: +55-51-33598293 Fax: +55-51-33598293
Received: October 20, 2014
Peer-review started: October 20, 2014
First decision: December 11, 2014
Revised: January 6, 2015
Accepted: February 13, 2015
Article in press: February 13, 2015
Published online: August 7, 2015
Processing time: 292 Days and 5.7 Hours
AIM: To evaluate the nutritional status and its association with proinflammatory cytokines in children with chronic liver disease.
METHODS: We performed a cross-sectional study with 43 children and adolescents, aged 0 to 17 years, diagnosed with chronic liver disease. All patients regularly attended the Pediatric Hepatology Unit and were under nutritional follow up. The exclusion criteria were fever from any etiology at the time of enrollment, inborn errors of the metabolism and any chronic illness. The severity of liver disease was assessed by Child-Pugh, Model for End-stage Liver Disease (MELD) and Pediatric End Stage Liver Disease (PELD) scores. Anthropometric parameters were height/age, body mass index/age and triceps skinfold/age according to World Health Organization standards. The cutoff points for nutritional status were risk of malnutrition (Z-score < -1.00) and malnutrition (Z-score < -2.00). Interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α levels were assessed by commercial ELISA kits. For multivariate analysis, linear regression was applied to assess the association between cytokine levels, disease severity and nutritional status.
RESULTS: The median (25th-75th centile) age of the study population was 60 (17-116)-mo-old, and 53.5% were female. Biliary atresia was the main cause of chronic liver disease (72%). With respect to Child-Pugh score, cirrhotic patients were distributed as follows: 57.1% Child-Pugh A, a mild presentation of the disease, 34.3% Child-Pugh B, a moderate stage of cirrhosis and 8.6% Child-Pugh C, were considered severe cases. PELD and MELD scores were only above the cutoff point in 5 cases. IL-6 values were increased in patients at nutritional risk (34.9%) compared with those who were well-nourished [7.12 (0.58-34.23) pg/mL vs 1.63 (0.53-3.43) pg/mL; P = 0.02], correlating inversely with triceps skinfold-for-age z-score (rs = -0.61; P < 0.001). IL-6 levels were associated with liver disease severity assessed by Child-Pugh score (P = 0.001). This association remained significant after adjusting for nutritional status in a linear regression model.
CONCLUSION: High IL-6 levels were found in children with chronic liver disease at nutritional risk. Inflammatory activity may be related to nutritional status deterioration in these patients.
Core tip: Inflammatory activity has been suggested as a component of the pathogenesis of illness-related malnutrition. Several studies have evaluated proinflammatory cytokines in pediatric chronic liver disease, but none have addressed the possible association between these biomarkers and nutritional status. This study showed that the interleukin-6 levels were significantly increased in children and adolescents at nutritional risk. To the best of our knowledge, this is the first study to analyze the relationship between the cytokine levels and nutritional status in children and adolescents with chronic liver disease.
