Background/Aims: It was suggested that serum pentraxin 3 (PTX3) levels could differentiate obese children with nonalcoholic steatohepatitis (NASH) from those with simple steatosis. Thus, we aimed to evaluate the clinical utility of serum PTX3 fragment levels in the diagnosis of NASH and the assessment of its severity in obese children with suspected nonalcoholic fatty liver disease (NAFLD). Methods: Fifty obese children were compared to 25 matched controls. All were subjected to history taking, anthropometric measurements, and abdominal ultrasonography, as well as laboratory assessments of liver functions, fasting lipid profile, fasting blood glucose, fasting insulin, homeostasis model assessment (HOMA) index, fasting glucose/insulin ratio, and serum PTX3. Results: PTX3 was higher in obese cases than controls (p = 0.0001). Eighty percent of the cases had NAFLD with progressive increases in PTX3 levels as the severity of fatty liver increased (p = 0.0001). Moreover, PTX3 was higher in cases with elevated liver enzymes (3.205 ± 0.77 U/l) than those with normal liver enzymes (2.77 + 0.69 U/l, p < 0.0001). A cutoff value of 3.03 U/l differentiated fatty liver from NASH with a sensitivity of 89% and a specificity of 86%. Conclusion: Noninvasive monitoring of serum PTX3 fragment levels in obese patients with suspected NAFLD may be used as a reliable tool for differentiating NASH from simple fatty liver.

Keywords:
Children, Fatty liver, Nonalcoholic steatohepatitis, Obesity, Pentraxin 3
1.
Fraser A, Longnecker MP, Lawlor DA: Prevalence of elevated alanine aminotransferase among US adolescents and associated factors: NHANES 1999-2004. Gastroenterology 2007;133:1814-1820.
2.
Patton HM, Unalp A, Yates J, et al: Metabolic syndrome among children with variable features of nonalcoholic fatty liver disease (abstract). Hepatology 2007;46:730A.
3.
Alisi A, Manco M, Vania A, Nobili V: Pediatric nonalcoholic fatty liver disease in 2009. J Pediatr 2009;155:469-474.
4.
Rafiq N, Younossi ZM: Nonalcoholic fatty liver disease: a practical approach to evaluation and management. Clin Liver Dis 2009;13:249-266.
5.
Wieckowska A, Feldstein AE: Diagnosis of nonalcoholic fatty liver disease: invasive versus noninvasive. Semin Liver Dis 2008;28:386-395.
6.
Lurie Y, Webb M, Cytter-Kuint R, Shteingart S, Lederkremer GZ: Non-invasive diagnosis of liver fibrosis and cirrhosis. World J Gastroenterol 2015;21:11567-11583.
7.
Mantovani A, Garlanda C, Bottazzi B, Peri G, Doni A, Martinez de la Torre Y, Latini R: The long pentraxin PTX3 in vascular pathology. Vascul Pharmacol 2006;45:326-330.
8.
Fazzini F, Peri G, Doni A, Dell'Antonio G, Dal Cin E, Bozzolo E, D'Auria F, Praderio L, Ciboddo G, Sabbadini MG, Manfredi AA, Mantovani A, Querini PR: PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation. Arthritis Rheum 2001;44:2841-2850.
9.
Yoneda M, Uchiyama T, Kato S, Endo H, Fujita K, Yoneda K, Mawatari H, Ijda H, Takahashi H, Kirikoshi H, Inamori M, Nozaki Y, Kobayashi N, Kubota K, Saito S, Maeyama S, Saraga M, Aburatani H, Kodama T, Nakajima A: Plasma pentraxin 3 is a novel marker for nonalcoholic steatohepatitis (NASH). BMC Gastroenterol 2008;8:53.
10.
Cole TJ: A chart to link child centiles of body mass index, weight and height. Eur J Clin Nutr 2002;56:1194-1199.
11.
Hockenberry MJ, Hinds PS, Barrera P, Bryant R, Adams-McNeill J, Hooke C, et al: Three instruments to assess fatigue in children with cancer: the child, parent and staff perspectives. J Pain Symptom Manage 2003;25:319-328.
12.
Chervin RD, Hedger K, Dillon JE, Pituch KJ: Pediatric Sleep Questionnaire (PSQ): validity and reliability of scales for sleep-disordered breathing, snoring, sleepiness, and behavioral problems. Sleep Med 2000;1:21-32.
13.
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents: The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004;114(suppl 4th report):555-576.
14.
Tanner JM, Whitehouse RH, Takaishi M: Standards from birth to maturity for height, weight, height velocity, and weight velocity: British children, 1965. Arch Dis Child 1966;41:454-613.
15.
Eisenmann JC: Waist circumference percentiles for 7- to 15-year-old Australian children. Acta Paediatr 2005;94:1182-1185.
16.
Cole TJ, Green PJ: Smoothing reference centile curves: the LMS method and penalized likelihood. Stat Med 1992;11:1305-1319.
17.
Kissebah AH, Vydelingum N, Murray R, Evans DJ, Hartz AJ, Kalkhoff RK: Relation of body fat distribution to metabolic complications of obesity. J Clin Endocrinol Metab 1982;54:254-260.
18.
Plan and operation of the Third National Health and Nutrition Examination Survey, 1988-1994. Series 1: programs and collection procedures. Vital Health Stat 1 1994;32:1-407.
19.
Troiano RP, Flegal KM, Kuczmarski RJ, Campbell SM, Johnson CL: Overweight prevalence and trends for children and adolescents. The National Health and Nutrition Examination Surveys, 1963 to 1991. Arch Pediatr Adolesc Med 1995;149:1085-1091.
20.
International Society for the Advancement of Kinanthropometry (ISAK): International Standards for Anthropometric Assessment. Underdale, ISAK, 2001.
21.
Tanner JM, Whitehouse RH: Clinical longitudinal standards for height, weight, height velocity, weight velocity and stages of puberty. Arch Dis Child 1976;51:170-179.
22.
Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
23.
Highlights of the report of the expert panel on blood cholesterol levels in children and adolescents. National Cholesterol Education Program Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Am Fam Physician 1992;45:2127-2136.
24.
Young-Hyman D, Schlundt DG, Herman L, De Luca F, Counts D: Evaluation of the insulin resistance syndrome in 5- to 10-year-old overweight/obese African-American children. Diabetes Care 2001;24:1359-1364.
25.
Sacks DB: Carbohydrates; in Burtis CA, Ashwood ER (eds): Tietz Textbook of Clinical Chemistry, ed 2. Philadelphia, Saunders, 1994, pp 750-808.
26.
Legro RS, Finegood D, Dunaif A: A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1998;83:2694-2698.
27.
Madeira IR, Carvalho CN, Gazolla FM, de Matos HJ, Borges MA, Bordallo MA: Cut-off point for Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index established from Receiver Operating Characteristic (ROC) curve in the detection of metabolic syndrome in overweight pre-pubertal children (in Portuguese). Arq Bras Endocrinol Metabol 2008;52:1466-1473.
28.
Kotooka N, Inoue T, Fujimatsu D, Morooka T, Hashimoto S, Hikichi Y, Uchida T, Sugiyama A, Node K: Pentraxin3 is a novel marker for stent-induced inflammation and neointimal thickening. Atherosclerosis 2008;197:368-374.
29.
Chu SH, Park JH, Lee MK, Jekal Y, Ahn KY, Chung JY, Lee DH, Kim ES, et al: The association between pentraxin 3 and insulin resistance in obese children at baseline and after physical activity intervention. Clin Chim Acta 2012;413:1430-1437.
30.
Ma X, Holalkere NS, Kambadakone RA, Mino-Kenudson M, Hahn PF, Sahani DV: Imaging-based quantification of hepatic fat: methods and clinical applications. Radiographics 2009;29:1253-1277.
31.
Farrell GC: Non-alcoholic steatohepatitis: what is it, and why is it important in the Asia-Pacific region? J Gastroenterol Hepatol 2003;18:124-138.
32.
Angulo P: Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221-1231.
33.
Cadranel JF: Good clinical practice guidelines for fine needle aspiration biopsy of the liver: past, present and future (in French). Gastroenterol Clin Biol 2002;26:823-824.
34.
Sakugawa H, Nakayoshi T, Kobashigawa K, Yamashiro T, Maeshiro T, Miyagi S, Shiroma J, Toyama A, Nakayoshi T, Kinjo F, Saito A: Clinical usefulness of biochemical markers of liver fibrosis in patients with nonalcoholic fatty liver disease. World J Gastroenterol 2005;11:255-259.
35.
Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, et al: Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003;37:917-923.
36.
Fong DG, Nehra V, Lindor KD, Buchman AL: Metabolic and nutritional considerations in nonalcoholic fatty liver. Hepatology 2000;32:3-10.
37.
Vajro P, Mandato C, Franzese A, et al: Vitamin E treatment in pediatric obesity-related liver disease: a randomized study. J Pediatr Gastroenterol Nutr 2004;38:48-55.
38.
Tazawa Y, Noguchi H, Nishinomiya F, Takada G: Serum alanine aminotransferase activity in obese children. Acta Paediatr 1997;86:238-241.
39.
Bergomi A, Lughetti L, Corciulo N: Italian multicenter study on liver damage in pediatric obesity. Int J Obes Relat Metab Disord 1998;22(suppl 4):S22.
40.
Eminoğlu TF, Camurdan OM, Oktar SO, Bideci A, Dalgiç B: Factors related to non-alcoholic fatty liver disease in obese children. Turk J Gasteroenterol 2008;19:85-91.
41.
Lee KH, Park SH, Kim YJ, Huh KR, Min KS, Jun SY, Kim KO, Park CH, Hahn T, Yoo KS, Kim JH, Lee MS, Park CK: Validity and reliability of the nonalcoholic fatty liver diseases activity score (NAS) in Korean NAFLD patients and its correlation with clinical factors (in Korean). Korean J Hepatol 2010;16:29-37.
42.
Rocha R, Cotrim HP, Carvalho FM, Siqueira AC, Braga H, Freitas LA: Body mass index and waist circumference in non-alcoholic fatty liver disease. J Hum Nutr Diet 2005;18:365-370.
43.
Zaini WMWN: Fatty liver in obese children: a study of ultrasonography and liver enzyme levels (abstract). Med J Malaysia 2011;66S:5.
44.
Franzese A, Vajro P, Argenziano A, Puzziello A, Iannucci MP, Saviano MC, Brunetti F, Rubino A: Liver involvement in obese children. Ultrasonography and liver enzyme levels at diagnosis and during follow-up in an Italian population. Dig Dis Sci 1997;42:1428-1432.
45.
Breviario F, d'Aniello EM, Golay J, Peri G, Bottazzi B, Bairoch A, Saccone S, Marzella R, Predazzi V, Rocchi M, et al: Interleukin-1-inducible genes in endothelial cells. Cloning of a new gene related to C-reactive protein and serum amyloid P component. J Biol Chem 1992;267:22190-22197.
46.
Garlanda C, Bottazzi B, Bastone A, Mantovani A: Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Annu Rev Immunol 2005;23:337-366.
47.
Kirsch R, Clarkson V, Verdonk RC, Marais AD, Shephard EG, Ryffel B, de la M Hall P: Rodent nutritional model of steatohepatitis: effects of endotoxin (lipopolysaccharide) and tumor necrosis factor alpha deficiency. J Gastroenterol Hepatol 2006;21(pt 1):174-182.
48.
Barazzoni R, Palmisano S, Gortan Cappellari G, Giuricin M, Moretti E, Vinci P, Semolic A, Guarnieri G, Zanetti M, Manzini Nd: Gastric bypass-induced weight loss alters obesity-associated patterns of plasma pentraxin-3 and systemic inflammatory markers. Surg Obes Relat Dis 2016;12:23-32.
49.
Latini R, Maggioni AP, Peri G, Gonzini L, Lucci D, Mocarelli P, Vago L, Pasqualini F, Signorini S, Soldateschi D, Tarli L, Schweiger C, Fresco C, Cecere R, Tognoni G, Mantovani A; Lipid Assessment Trial Italian Network (LATIN) Investigators: Prognostic significance of the long pentraxin PTX3 in acute myocardial infarction. Circulation 2004;110:2349-2354.
50.
Sanyal AJ, Campbell-Sargent C, Mirshahi F, Rizzo WB, Contos MJ, et al: Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001;120:1183-1192.
51.
Sanyal AJ; American Gastroenterological Association: AGA technical review on nonalcoholic fatty liver disease. Gastroenterology 2002;123:1705-1725.
52.
Rovere P, Peri G, Fazzini F, Bottazzi B, Doni A, Bondanza A, Zimmermann VS, Garlanda C, Fascio U, Sabbadini MG, Rugarli C, Mantovani A, Manfredi AA: The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen-presenting dendritic cells. Blood 2000;96:4300-4306.
53.
Violi F, Pastori D: Pentraxin 3 - a link between obesity, inflammation and vascular disease? Circ J 2016;80:327-328.
54.
Menon PS: Childhood obesity, metabolic syndrome and Pentraxin-3. Indian J Pediatr 2015;82:3-4.
55.
Parlak A, Aydoğan Ü, İyisoy A, Dikililer M, Kut A, Cakır E, Sağlam K: Elevated pentraxin-3 levels are related to blood pressure levels in hypertensive patients: an observational study. Anadolu Kardiyol Derg 2012;12:298-304.
56.
Alberti L, Gilardini L, Zulian A, et al: Expression of long pentraxin PTX3 in human adipose tissue and its relation with cardiovascular risk factors. Atherosclerosis 2009;202:455-460.
57.
Tilg H, Moschen AR: Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 2006;6:772-783.
© 2016 S. Karger AG, Basel
2016
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.