Original article 739 Serum ghrelin, adipokine and insulin levels in children with acute hepatitis Gergely To ´ th a , Manfred Rauh b , Zolta ´n Nyul a , Endre Sulyok a and Wolfgang Rascher b Objectives Recent reports suggest that adipokines are potent modulators of inflammation. We tested the hypothesis that the decreased food intake and the acute liver disease might be associated with changes of serum ghrelin, adipokines and insulin levels. Methods Fasting ghrelin, adiponectin, leptin, resistin and insulin were measured in 25 children suffering from acute viral hepatitis, caused by either hepatitis A or Epstein–Barr viruses. The age of the patients ranged from 2.2 to 17.2 years (mean: 10.4 years); 10 male and 15 female. Samples for hormones and liver function tests were drawn at 08 : 00 to 09 : 00 h after an overnight fast. The first samples were collected in the morning after the day of admission, the second samples after 2 months of recovery. Results Ghrelin and adiponectin levels were significantly higher during hepatitis than after recovery (831.4 ± 276.44 vs. 736.21 ± 274.91 pg/ml, P < 0.0001; and 22.91 ± 12.93 vs. 15.16 ± 8.81 lg/ml, P < 0.001, respectively). Adiponectin levels correlated significantly with age-specific and sex-specific body mass index-matched percentile values as well (P = 0.0062). Linear regression analysis confirmed that there was a significant association of changes in serum ghrelin and resistin levels and the severity of hepatitis (P = 0.005; P < 0.05). We could verify a marginal relationship of the changes of serum leptin and the severity of the disease (P = 0.0646). Conclusion This study confirms that there are significant changes in serum levels of ghrelin, and adipokines in disease-associated malnutrition and acute hepatitis. Eur J Gastroenterol Hepatol 21:739–743  c 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins. European Journal of Gastroenterology & Hepatology 2009, 21:739–743 Keywords: adipokine, childhood, ghrelin, hepatitis a Institute of Health Promotion and Family Care, University of Pe ´ cs, Hungary and b Clinic for children and adolescents, University of Erlangen, Erlangen, Germany Correspondence to Gergely To ´ th, MD, Kerpel-Fronius O ¨ do ¨ n County Children’s Hospital Pe ´ cs, Nya ´r u. 8, Pe ´cs H-7624, Hungary Tel: +36 72 518 533; fax: +36 72 213 042; e-mail: drtothg@freemail.hu Received 16 March 2008 Accepted 24 June 2008 Introduction Since the discovery of several adipocyte-derived factors, designated as adipokines, adipose tissue has been regarded as an active player in the regulation of meta- bolism [1]. In this context, numerous substances, released by the adipose tissue including tumour necrosis factor-a, leptin, resistin and adiponectin are interrelated and are thought to contribute to metabolic changes in chronic liver disorders [2–5]. Ghrelin is a recently identified enteric hormone that has profound orexigenic, adipogenic and somatotropic proper- ties; it increases food intake and body weight. It is secreted predominantly by the stomach. Ghrelin acts through the activation of the hypothalamic nuclei and the promotion of neuropeptide Y and agouti-related protein expression [6,7]. Ghrelin administration stimu- lates growth hormone secretion independent of hypotha- lamic growth hormone-releasing hormone, and also causes weight gain and adiposity by increasing food intake and reducing fat utilization in rodents [8,9]. The wide tissue distribution of ghrelin, however, suggests that it may have other functions as well. It also enhances immune responses and potentially downregulates anti- inflammatory molecules [10]. Adiponectin is the most abundant circulating adipokine in both mice and humans [11]. Several cell types, including macrophages, express adiponectin receptors [12]. Adiponectin directly affects the inflammatory res- ponse by regulating both the production and the activity of cytokines [13–15] and can also act as an anti- apoptotic agent in a variety of cell types [16–18]. In fact, recent data indicate that adiponectin plays an anti- inflammatory role in both acute and chronic inflammatory liver disease in vivo in mice [19–21]. Leptin is a peptide hormone and is predominantly produced by adipocytes [22]. It is postulated to regulate energy balance by suppressing appetite and increasing energy expenditure [23–25]. The mechanism of action in the hypothalamic nuclei is antagonistic to ghrelin: leptin inhibits neuropeptide Y and agouti-related protein [26]. Moreover, leptin also plays a role in the modulation of immune response and inflammation. The increase in leptin production that occurs during infection and 0954-691X  c 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/MEG.0b013e32830dfcca Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.