Serum proinflammatory cytokines and nutritional status in pediatric chronic liver disease.
OBJECTIVE
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 (25(th)-75(th) 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.


CONCLUSIONS
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.
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.
Daniele
D
Santetti
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.
Maria Inês
MI
de Albuquerque Wilasco
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
CT
Dornelles
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.
Isabel Cristina Ribas
IC
Werlang
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.
Fernanda Urruth
FU
Fontella
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.
Carlos Oscar
CO
Kieling
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.
Jorge Luiz
JL
Dos Santos
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.
Sandra Maria Gonçalves
SM
Vieira
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.
Helena Ayako Sueno
HA
Goldani
D000293:Adolescent; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D002648:Child; D002664:Child Nutritional Physiological Phenomena; D002675:Child, Preschool; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007223:Infant; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D008107:Liver Diseases / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D008297:Male; D044342:Malnutrition / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D015999:Multivariate Analysis; D015596:Nutrition Assessment; D009752:Nutritional Status; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D015854:Up-Regulation
D015415:Biomarkers; D016207:Cytokines; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6
Child; Cirrhosis; Cytokines; Interleukin-6; Malnutrition