Gastroenterol Res
Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access
Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc
Journal website http://www.gastrores.org

Original Article

Volume 7, Number 5-6, December 2014, pages 131-136


Assessment of Growth and Development in Children With Hepatitis B Positivity

Tugba Saria, c, Erdal Erenb, Suda Tekin Koruka

aDepartment of Infectious Diseases and Clinical Microbiology, Harran University School of Medicine, 63100 Sanliurfa, Turkey
bDepartment of Pediatric Endocrinology, Harran University School of Medicine, 63100 Sanliurfa, Turkey
cCorresponding Author: Tugba Sari, Department of Infectious Diseases and Clinical Microbiology, Harran University School of Medicine, 63100 Sanliurfa, Turkey

Manuscript accepted for publication August 26, 2014
Short title: Hepatitis B Positivity
doi: https://doi.org/10.14740/gr628e

Abstract▴Top 

Background: Chronic infections and liver diseases may influence the growth and development of children by leading to malnutrition. In this study, demographic characteristics, anthropometric measurements and laboratory findings for children with hepatitis B positivity were analyzed.

Methods: A total of 43 cases were admitted to our clinic between January 2012 and February 2013 and detected to have HBsAg positivity.

Results: Malnutrition was detected in 11 cases (25.6%) and obesity in three cases (6.9%). Aspartate aminotransferase (AST) levels were significantly higher in malnourished patients compared to those without malnutrition. The weight to height was significantly higher in patients with positive HBeAg compared to children with negative HBeAg. We found that the weight standard deviation scores (SDS) ratios dropped as alanine aminotransferase (ALT) and AST levels increased and height SDS ratios decreased. In addition, body mass index (BMI) decreased as AST and alpha feto protein (AFP) values increased. While a significant relationship was not detected between insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) and ALT, a significantly negative correlation was detected between IGFBP-3 and IGF-1 and AST. We found a malnutrition rate of 25.6% in children with HBsAg positivity. We also found that weight and height SDS rates decreased as ALT and AST levels increased. In addition, we detected that BMI decreased as AST and AFP values increased.

Conclusion: We consider that hepatic inflammation is the factor that affects growth. Monitoring of growth and development during follow-up of children who are detected to have HBsAg positivity would be beneficial to determine the mechanism and causes of growth retardation.

Keywords: Hepatitis B; Children; Body weight; Body height

Introduction▴Top 

Children’s growth is a multifactorial process involving genetic and environmental factors. Infections, particularly of gastrointestinal origin, may lead to anorexia, reduction in energy and metabolic rate and malnutrition [1-3]. Malnutrition makes children susceptible to infections through a vicious cycle [4-10]. Chronic infections and liver diseases may influence the growth and development of children by leading to malnutrition [4-10]. Anorexia, impaired nutritional habits and impaired insulin-like growth factor (IGF) release are the most common causes of malnutrition in chronic liver diseases [5-8]. The hepatitis B virus (HBV) is an important health problem in our country and in the world, as it leads to chronic hepatitis, hepatic cirrhosis and hepatocellular carcinoma, in addition to acute hepatitis [11]. In this study, demographic characteristics, anthropometric measurements and laboratory findings for children with hepatitis B positivity were analyzed.

Methods▴Top 

This was a prospective cohort study implemented from January 2012 to February 2013 in Sanliurfa, Turkey. A total of 43 cases who were admitted to Infectious Diseases and Clinical Microbiology Clinic and detected to have HBsAg positivity, in whom acute viral hepatitis was excluded with serologic tests were randomly enrolled in the study. The height, weight and body mass index (BMI) of patients and the standard deviation scores (SDS) of these parameters were evaluated. Ethics committee approval was obtained for this study investigating the influence of HBsAg positivity on growth in children. The height and weight of all participants were measured. The weight measurement was done using a weighing scale sensitive to 100 g. The height measurement was done with 0.5 cm sensitivity. The individual percentile values of children were determined. BMI (kg/m2) was calculated. These values were compared with those determined by Neyzi et al [12] for Turkish children. Children with a weight to height value below 90% were accepted as malnourished, and those above 120% were accepted as obese [13]. Serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) were studied. A DSL-5600 ActiveTM IGF-1 IRMA kit and a DSL-6600 ActiveTM IGFBP-3 IRMA kit were used in a Berthold Lb 2111 12 detector gamma counter device for analysis (Diagnostic System Laboratories Inc., Webster, TX, USA). HBV DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), IGF-1, IGFBP-3, total bilirubin, direct bilirubin, alpha feto protein (AFP) and HBeAg positivity were also examined. The normal laboratory values and methods are given in Table 1.

Table 1.
Click to view
Table 1. Normal Values and Laboratory Procedures
 

Patients were evaluated according to biopsy results, ultrasonography findings, HBV DNA negativity spontaneously or through treatment, ALT normalization and HBeAg seroconversion. Modified Knodell scoring was used for histopathologic staging in chronic patients [14]. Patients with ALT more than two-fold of normal values and HBV DNA > 2,000 IU/mL were accepted as chronic hepatitis B. Those whose HBeAg was positive and ALT level was normal but HBV DNA > 2,000 IU/mL were accepted as immune tolerant. Those whose HBeAg was negative and ALT level was normal and HBV DNA < 2,000 IU/mL were accepted as carriers [15]. Patients who had malabsorption, growth hormone deficiency and syndromes were excluded from the study. The SPSS 15.0 statistical package program was used for statistical analysis. Pearson’s correlation test, the Chi-square test and the t-test were used for data analysis. A P level of < 0.05 was accepted as statistically significant.

Results▴Top 

Of the patients enrolled in the study, 17 (39.5%) were girls, and the mean age of the patients was 10.81 ± 3.23 years; the mean age at the time of diagnosis was 7.27 ± 3.45 years. The mean duration of follow-up at our clinic was 35.16 ± 24.8 months. There was a family history of hepatitis B in 37 (86%) patients; hepatitis B positivity was detected in the mother in 25 (58.1%) patients and in at least one sibling in 28 (65.1%) patients. All patients had similar family properties with low socioeconomic status. The demographic characteristics of patients are given in Table 2.

Table 2.
Click to view
Table 2. Features of Children Diagnosed With Hepatitis B
 

The height, weight and BMI of patients and the SDS of the parameters were analyzed. While the SDS for height was below -2 in one child with HBsAg positivity, the SDS for weight was below -2 in three.

HBeAg was positive in 29 of 43 participants (67.4%), and AntiHBe was positive in 14 (32.6%). Of the cases, 14 (42.6%) were carriers, 13 (30.2%) were chronic patients and 16 (37.2%) were immune tolerant. The laboratory findings of patients are given in Table 3.

Table 3.
Click to view
Table 3. Laboratory Findings of Patients
 

Malnutrition was detected in 11 cases (25.6%) and obesity in three cases (6.9%). Patients with and without malnutrition are compared in Table 4. While malnutrition was detected in 11 (n = 37) (29.7%) of the patients with a family history of hepatitis B, malnutrition was detected in none of the children without a family history of hepatitis B (n = 6). AST levels were significantly higher in malnourished patients compared to those without malnutrition (P = 0.004).

Table 4.
Click to view
Table 4. Comparison of Mean Laboratory Findings of Children With or Without Malnutrition
 

ALP and GGT levels were found to increase as HBV DNA values increased (P = 0.02, P < 0.001). The HBV DNA and AST values of HBeAg-positive children were significantly greater (P < 0.001, P = 0.02). The ALT level was significantly higher in children with negative HBeAg (P = 0.007). The weight to height was significantly higher in patients with positive HBeAg compared to children with negative HBeAg (P = 0.03). We found that the weight SDS ratios dropped as ALT and AST levels increased (P = 0.048, P < 0.001) and height SDS ratios decreased (P = 0.015, P = 0.014). In addition, BMI decreased as AST and AFP values increased (P = 0.009, P = 0.001).

The IGF-1 level was studied in 32 patients, and IGFBP-3 was studied in 33 patients. The IGF-1 level was significantly lower in malnourished patients (P = 0.031). While a significant relationship was not detected between IGFBP-3 and IGF-1 and ALT, a significantly negative correlation was detected between IGFBP-3 and IGF-1 and AST (P = 0.01, P = 0.013).

Liver biopsy was performed in six (14%) patients. The results were as follows: histological activity index (HAI): 1 (n = 1), HAI: 5 (n = 1), HAI: 6 (n = 2), HAI: 8 (n = 2), fibrosis: 1 (n = 3), fibrosis: 2 (n = 1), fibrosis: 3 (n = 2). Malnutrition was detected in one of them (HAI = 6). HBV DNA became negative in two out of six patients who were treated (4.7%), ALT became normal in four (9.3%) and HBeAg seroconversion was detected in two (4.7%). In untreated patients, HBV DNA became negative spontaneously during follow-up in one patient (2.3%), ALT became normal in 10 (23.3%) and HBeAg seroconversion was seen in two (4.7%).

Hepatobiliary ultrasonography revealed normal findings in 40 children (93%), rough granular appearance in 2 (4.7%) and gallbladder stone in 1 (2.3%).

Discussion▴Top 

Vertical contamination from an infected mother to a child is the main source of infection in many endemic countries [16, 17]. HBV infection causes infection mainly via non-parenteral routes in moderately endemic countries such as our country [18, 19]. In our study, there was a history of hepatitis B in the families of 37 patients (86%); HBsAg positivity was detected in the mother in 25 of them (58.1%) and in at least one sibling in 28 (65.1%).

Food intake is reduced and food loss is increased in all infectious diseases due to impaired intestinal absorption and increased intestinal excretion [10]. Reduced calorie intake, malabsorption and chronic liver diseases affect IGF production from the liver, or inflammatory mediators may affect growth [20].

In addition, the elevation of inflammatory cytokines may affect anorexia [10, 21, 22]. Another important mechanism is catabolic processes, which continue during infections, negatively affecting growth [10]. The immune stimulant effect of subclinical infections may also lead to malnutrition in developing countries [10, 23]. Growth retardation is among the rare outcomes of chronic hepatitis B [4-10]. Regulation of the liver metabolism plays an important role in food homeostasis and absorption [5-8].

Chronic infections and chronic liver diseases are known to lead to malnutrition through different mechanisms [4-10]. However, growth retardation has been rarely reported in chronic hepatitis B [24, 25]. Growth retardation has been detected in children who were diagnosed with chronic hepatitis B and received interferon treatment [26, 27]. A malnutrition rate of 21% was found in another study carried out with 3,152 preschool children [28]. In the study of Kuloglu et al [29], hepatitis B was found not to affect growth and development. We found a malnutrition rate of 25.6% in children with HBsAg positivity. We also found that weight and height SDS rates decreased as ALT and AST levels increased. In addition, we detected that BMI decreased as AST and AFP values increased. We consider that hepatic inflammation is the factor that affects growth.

Children’s living in rural areas, having families with low education level, low socioeconomic level, poor hygiene and having many siblings negatively affect their nutritional status. HBV seroprevalence is high in rural areas that have a low socioeconomic level [28].

Of our patients, 32.6% were inactive carriers, 30.2% were chronic hepatitis B patients and 37.2% were in an immune tolerant phase. Most of the immune tolerant children had been affected via the perinatal route. T cells’ likelihood of infecting hepatocytes is lower, as their immune system has not been fully developed. Therefore, these children pass to an immune competent phase after decades as they develop normal transaminase levels [20, 30-32].

HIV positivity was shown to affect growth and development negatively in correlation with viral load [33]. In our study, HBV load was not found to be correlated with growth and development.

Growth hormone’s anabolic and growth accelerating effects are realized through IGF-1 and IGFBP-3. IGF-1 is mainly released from liver and peripheral tissues, and IGF-1 level measurement may be used to determine growth hormone deficiency. Serum IGF-1 and IGFBP-3 levels are affected by chronological age, sexual maturity and nutritional status [34, 35]. In the study of Colakoglu et al [36], IGF-1 and IGDBP-3 levels were found to be significantly lower in 42 cirrhotic patients compared to non-cirrhotic ones. We detected that IGF-1 and IGFBP-3 values decreased as AST levels increased.

We found that HBV infection affected the development of children. Generally, elevated AST levels were effective, in development of children and we aimed to emphasize that this infection should be kept in mind while researching developmental anomalies. Monitoring of growth and development during follow-up of children who are detected to have HBsAg positivity would be beneficial to determine the mechanism and causes of growth retardation.

Conflict of Interest

The authors have no commercial conflicts of interest to declare.

Financial Support

No.

Author Note

The present address of Tugba Sari is Infectious Diseases and Clinical Microbiology Department, Buldan Chest Diseases Hospital, 20400 Denizli, Turkey.


References▴Top 
  1. Zenel JA, Jr. Failure to thrive: a general pediatrician's perspective. Pediatr Rev. 1997;18(11):371-378.
    pubmed
  2. Marcovitch H. Failure to thrive. BMJ. 1994;308(6920):35-38.
    doi pubmed
  3. Roy CC, Silverman A, Alagille D. Symptoms. In: Roy CC, Silverman A, Alagille D, editors. Pediatric clinical gastroenterology. 4th ed. London: Mosby. 1995;3-10.
  4. Doherty C, Reilly J, Paterson W et al: Growth failure. In: Walker WA, Goulet O, Kleinman RE editors. Pediatric gastrointestinal disease: pathophysiology, diagnosis, management. 4th Ed. Ontario: BC Decker Inc. 2004;281-296.
    pubmed
  5. Shepherd RW, Ramm GA: Fibrogenesis and cirrhosis. In: Walker WA, Goulet O, Kleinman RE, Sherman PM, Schneider BL, Sanderson IR, editors. Pediatric gastrointestinal disease: pathophysiology, diagnosis, management. 4th ed. Ontario: BC Decker Inc. 2004;80-88.
  6. Mager DR, Wykes LJ, Roberts EA, Ball RO, Pencharz PB. Mild-to-moderate chronic cholestatic liver disease increases leucine oxidation in children. J Nutr. 2006;136(4):965-970.
    pubmed
  7. Mager DR, Wykes LJ, Roberts EA, Ball RO, Pencharz PB. Branched-chain amino acid needs in children with mild-to-moderate chronic cholestatic liver disease. J Nutr. 2006;136(1):133-139.
    pubmed
  8. Bavdekar A, Bhave S, Pandit A. Nutrition management in chronic liver disease. Indian J Pediatr. 2002;69(5):427-431.
    doi pubmed
  9. Tsiaousi ET, Hatzitolios AI, Trygonis SK, Savopoulos CG. Malnutrition in end stage liver disease: recommendations and nutritional support. J Gastroenterol Hepatol. 2008;23(4):527-533.
    doi pubmed
  10. Bhutta ZA. Effect of infections and environmental factors on growth and nutritional status in developing countries. J Pediatr Gastroenterol Nutr. 2006;43(Suppl 3):S13-21.
    doi pubmed
  11. Tasyaran MA. The epidemiology of HBV infection. Kilicturgay K, Badur S editors. Journal of Viral hepatitis. Istanbul: The association of Viral hepatitis. 2013;121-128.
  12. Neyzi O, Gunoz H, Furman A et al. Body weight, height, head circumference and body mass index reference values for Turkish children. Journal of children health and diseases. 2008;51(1):1-14.
  13. Waterlow JC. Classification and definition of protein-calorie malnutrition. Br Med J. 1972;3(5826):566-569.
    doi pubmed
  14. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22(6):696-699.
    doi
  15. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 2012;57(1):167-185.
    pubmed
  16. http://www.who.int/immunization_monitoring/Global_Immunization_Data.pdf.
  17. Chan OK, Lao TT, Suen SS, Leung TY. Deficient knowledge on hepatitis B infection in pregnant women and prevalence of hepatitis B surface antigen carriage in an endemic area: a review. Hepat Res Treat. 2012;2012:317451.
  18. Ersoy Y, Sonmez E, Cetin C et al. Hepatitis B virus transmission in the family. Journal of Turgut Ozal medical center. 1997;4(4):430-433.
  19. Ustun C, Basuguy E, Deveci U. Seroprevalence of hepatitis B and hepatitis C in children admitted to pediatric surgery policlinic. Online journal of Nobel medicus. http://www.nobelmedicus.com/contents/200956/04-09.htm.
  20. Gerner P, Horning A, Kathemann S, Willuweit K, Wirth S. Growth abnormalities in children with chronic hepatitis B or C. Adv Virol. 2012;2012:670316.
    doi pubmed
  21. Bhutta ZA, Mansoorali N, Hussain R. Plasma cytokines in paediatric typhoidal salmonellosis: correlation with clinical course and outcome. J Infect. 1997;35(3):253-256.
    doi
  22. Campbell DI, Elia M, Lunn PG. Growth faltering in rural Gambian infants is associated with impaired small intestinal barrier function, leading to endotoxemia and systemic inflammation. J Nutr. 2003;133(5):1332-1338.
    pubmed
  23. Solomons NW, Mazariegos M, Brown KH, Klasing K. The underprivileged, developing country child: environmental contamination and growth failure revisited. Nutr Rev. 1993;51(11):327-332.
    doi pubmed
  24. Polito C, La Manna A, Cartiglia ML, Bonomo G, Del Gado R. Normal growth of children with HBsAg positive chronic active hepatitis (CAH). Acta Paediatr Scand. 1991;80(12):1231-1232.
    doi pubmed
  25. Vegnente A, Guida S, Di Costanzo V, Fusco C, Iorio R, Toscano P. Nutritional status and growth in children with chronic hepatitis B. J Pediatr Gastroenterol Nutr. 1992;14(2):123-127.
    doi pubmed
  26. Jara P, Bortolotti F. Interferon-alpha treatment of chronic hepatitis B in childhood: a consensus advice based on experience in European children. J Pediatr Gastroenterol Nutr. 1999;29(2):163-170.
    doi
  27. Comanor L, Minor J, Conjeevaram HS, Roberts EA, Alvarez F, Bern EM, Goyens P, et al. Impact of chronic hepatitis B and interferon-alpha therapy on growth of children. J Viral Hepat. 2001;8(2):139-147.
    doi pubmed
  28. Tuncbilek E, Unalan T, Coskun T. Indicators of nutritional status in Turkish preschool children: results of Turkish Demographic and Health Survey 1993. J Trop Pediatr. 1996;42(2):78-84.
    doi pubmed
  29. Kuloglu Z, Kansu A, Demirceken F, Arici ZS, Berberoglu M, Ocal G, Girgin N. The influence of interferon-alpha and combination interferon-alpha and lamivudine therapy on height and weight in children with chronic hepatitis B infection. J Pediatr Endocrinol Metab. 2007;20(5):615-620.
    doi pubmed
  30. Milich DR, Jones JE, Hughes JL, Price J, Raney AK, McLachlan A. Is a function of the secreted hepatitis B e antigen to induce immunologic tolerance in utero? Proc Natl Acad Sci U S A. 1990;87(17):6599-6603.
    doi pubmed
  31. Chen MT, Billaud JN, Sallberg M, Guidotti LG, Chisari FV, Jones J, Hughes J, et al. A function of the hepatitis B virus precore protein is to regulate the immune response to the core antigen. Proc Natl Acad Sci U S A. 2004;101(41):14913-14918.
    doi pubmed
  32. Milich D, Liang TJ. Exploring the biological basis of hepatitis B e antigen in hepatitis B virus infection. Hepatology. 2003;38(5):1075-1086.
    doi pubmed
  33. Hilgartner MW, Donfield SM, Lynn HS, Hoots WK, Gomperts ED, Daar ES, Chernoff D, et al. The effect of plasma human immunodeficiency virus RNA and CD4(+) T lymphocytes on growth measurements of hemophilic boys and adolescents. Pediatrics. 2001;107(4):E56.
    doi pubmed
  34. Bar A, Tarasiuk A, Segev Y, Phillip M, Tal A. The effect of adenotonsillectomy on serum insulin-like growth factor-I and growth in children with obstructive sleep apnea syndrome. J Pediatr. 1999;135(1):76-80.
    doi
  35. Juul A, Bang P, Hertel NT, Main K, Dalgaard P, Jorgensen K, Muller J, et al. Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab. 1994;78(3):744-752.
    pubmed
  36. Colakoglu O, Taskiran B, Colakoglu G, Kizildag S, Ari Ozcan F, Unsal B. Serum insulin like growth factor-1 (IGF-1) and insulin like growth factor binding protein-3 (IGFBP-3) levels in liver cirrhosis. Turk J Gastroenterol. 2007;18(4):245-249.
    pubmed


This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Gastroenterology Research is published by Elmer Press Inc.

 

Browse  Journals  

     

Journal of clinical Medicine Research

Journal of Endocrinology and Metabolism

Journal of Clinical Gynecology and Obstetrics

World Journal of Oncology

Gastroenterology Research

Journal of Hematology

Journal of Medical Cases

Journal of Current Surgery

Clinical Infection and Immunity

Cardiology Research

World Journal of Nephrology and Urology

Cellular and Molecular Medicine Research

Journal of Neurology Research

International Journal of Clinical Pediatrics

 

 

 

 

 

Gastroenterology Research, bimonthly, ISSN 1918-2805 (print), 1918-2813 (online), published by Elmer Press Inc.        
The content of this site is intended for health care professionals.

This is an open-access journal distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons Attribution license (Attribution-NonCommercial 4.0 International CC-BY-NC 4.0)


This journal follows the International Committee of Medical Journal Editors (ICMJE) recommendations for manuscripts submitted to biomedical journals,
the Committee on Publication Ethics (COPE) guidelines, and the Principles of Transparency and Best Practice in Scholarly Publishing.

website: www.gastrores.org   editorial contact: editor@gastrores.org
Address: 9225 Leslie Street, Suite 201, Richmond Hill, Ontario, L4B 3H6, Canada

© Elmer Press Inc. All Rights Reserved.