Investigation of cardiomyopathy in children with cirrhotic and noncirrhotic portal hypertension.

BACKGROUND: Cirrhotic cardiomyopathy (CCMP) is a functional disorder characterized by electrophysiological disturbances, and diastolic and/or systolic dysfunction in patients with liver disease. This disorder is a well-defined entity in adults, but pediatric data are limited. The aim of the study was to determine the incidence, features, and risk factors of CCMP in children with portal hypertension (PHT). METHODS: This study included 50 children with cirrhotic PHT (40/50) and noncirrhotic PHT (10/50). Fifty healthy children were also selected for the control group. Electrocardiography and echocardiography were used to evaluate cardiac functions. Corrected QT (QTc) ≥ 0.45 was accepted as prolonged on electrocardiography. The study group was divided into 3 groups: cirrhotic, noncirrhotic, and control. Then, the CCMP group was created according to the diagnostic criteria. Latent CCMP was diagnosed in the presence of prolonged-QTc along with a minor criterion (tachycardia). Manifest CCMP was diagnosed in the presence of at least 2 major criteria (prolonged-QTc along with abnormal echocardiographic findings). Moreover, in this study, the risk factors for CCMP were investigated. RESULTS: The CCMP group included 10 cases (20%). Nine of these cases had latent CCMP (18%), and the remaining one (2%) had manifest CCMP. All of the cases with CCMP had cirrhosis and ascites. None of the patients with CCMP had severe cardiac symptoms, but they were already using some cardioprotective drugs such as propanolol and spironolactone. As risk factors for CCMP, pediatric end-stage liver disease scores, Child-Pugh scores, and ascites grades were found to be significant for the determination of CCMP. The most important risk factor was ascites severity (P = 0.001, odds ratio 9.4). CONCLUSIONS: Approximately 20% of children with PHT have CCMP. A detailed cardiac examination should be carried out periodically in children with cirrhotic PHT, especially in the presence of ascites and high Child-Pugh score.

Changing face and clinical features of celiac disease in children.

BACKGROUND: The aim of this study was to analyze and compare the epidemiological and presenting features, clinical patterns, and complications of celiac disease (CD) in children. METHODS: The clinical charts of children with CD were retrospectively analyzed. Data for children who presented during the first time period (January 2005-October 2008; group 1) were compared to those of children who presented during the second time period (November 2008-April 2012; group 2). RESULTS: Group 1 and 2 consisted of 96 and 95 children, respectively. There were no differences in gender distribution, weight, or height z-scores between the two groups. Mean age at the time of diagnosis in group 2 (9.3 ± 4.5 years) was significantly higher than in group 1 (6.9 ± 3.9 years; P < 0.001). Non-classical presentation was more frequent in group 2 (P = 0.01). Associated disorders were observed in 49 children (25.7%) overall. There were significantly more children with type 1 diabetes mellitus in group 2 (P = 0.030). In all, 11 patients (5.8%) were overweight (either obese or at risk of obesity) at presentation. Isolated short stature was the presenting feature in 15 children (7.9%) overall, but was more frequently observed in group 2 (P = 0.003). In total, 15 patients (7.9%) presented with refractory iron deficiency anemia; the frequency was similar in both groups. Dual-energy X-ray absorptiometry was performed in 102 patients, and 82 (80.4%) had metabolic bone disease (MBD). CONCLUSION: The mode of presentation and clinical features of CD in childhood continue to change. Of note, a substantial percentage of patients were overweight at presentation. MBD is a frequent complication, necessitating routine evaluation.

Rare causes of gastrointestinal hemorrhage in infancy.

Gastrointestinal hemorrhage in children is a critical condition that demands quick and effective management. The differential diagnosis of gastrointestinal hemorrhage is wide. Heterotopic pancreas is a rare congenital anomaly and usually discovered incidentally. It is generally asymptomatic, but symptoms may occur when complicated by inflammation, bleeding, obstruction or malign transformation. Heterotopic pancreas may present throughout the gastrointestinal tract, but it is most commonly found in the stomach, duodenum and proximal jejunum. Juvenile polyps are common during childhood and present most often with painless rectal hemorrhage. They remain the most common colonic polyps in children. Colonoscopic polypectomy is the most effective procedure in the treatment of juvenile polyps. In this study, we describe rare causes of gastrointestinal system hemorrhage in infancy and discuss some diagnostic and therapeutic approaches.

The relationship between pediatric nonalcoholic fatty liver disease and cardiovascular risk factors and increased risk of atherosclerosis in obese children.

To investigate the relationship between nonalcoholic fatty liver disease and cardiovascular risk factors and increased risk of atherosclerosis in obese children. The study included 80 consecutive obese children who were stratified into group 1 [ultrasonographically diagnosed with NAFLD (n = 50)] and group 2 [not diagnosed with NAFLD (n = 30)]. The control group included 30 healthy children. The groups were compared in terms of clinical cardiovascular risk factors and carotid intimal medial thickness (CIMT) (as a marker of atherosclerosis) measured using B-mode ultrasound. Mean body mass index (BMI) and blood pressure (BP), as well as the frequency of dyslipidemia, metabolic syndrome (MetS), and insulin resistance (IR), were similar in groups 1 and 2. Mean BMI and triglyceride (TG) levels, and the frequency of IR and MetS, increased significantly as the grade of steatosis increased. Mean CIMT in group 1 was significantly greater than that in the control group (P < 0.01). There was a positive correlation between CIMT and age, BP, and BMI in groups 1 and 2. In addition, CIMT was correlated with TG, low high-density lipoprotein (HDL) cholesterol, MetS, and IR only in group 1. Linear regression analysis between CIMT and age, BP, BMI, TG level, HDL cholesterol level, IR, MetS, and grade of steatosis yielded a significant difference only for grade of steatosis. Cardiovascular risk factors are more impressive and CIMT was significantly higher in group 1 than in group 2 and the control group, indicating that they are associated with greater risk of atherosclerosis and future adverse cardiovascular events.

Selective IgA deficiency: clinical and laboratory features of 118 children in Turkey.

Selective IgA deficiency (IgAD) is considered as the most common primary immunodeficiency. Although the vast majority of affected individuals are asymptomatic, symptomatic patients suffer from recurrent infections, allergies and autoimmune diseases. In the present study, we aimed to investigate the clinical and laboratory features of children with IgAD in a tertiary children's hospital in Turkey. The medical records of 118 patients (63 males, 55 females) aged 4-18 years (median: 7 years) seen from 2006 to 2011 were retrospectively reviewed. The most common clinical condition was infectious disease (99 patients, 83.9 %), followed by allergic (51 patients, 43.2 %) and autoimmune (20 patients, 17 %) disorders. Serum IgG, IgM and IgE levels were increased in 61 %, 22 % and 37.3 % of patients, respectively. Serum IgG subclasses were measured in 65 patients, and only 4 (6.2 %) patients had IgG2 subclass deficiency. Autoantibodies (ANA, anti-dsDNA, antigliadin IgA and IgG, tissue transglutaminase IgA and IgG, anti-TPO and anti-TG) were evaluated in 84 patients. Autoantibodies were detected in 26 (31 %) patients, only 10 had an autoimmune disorder. Sixty-one patients were followed for more than 6 months (mean: 2 years, range: 0.5-5 years), and none of them resolved during this period. Being the most comprehensive study conducted in Turkey, we believe it has importance in providing significant data on the clinical and laboratory characteristics of children with IgAD.

An unusual presentation of galactosemia: hemophagocytic lymphohistiocytosis.

UNLABELLED: Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening condition. Uncontrolled proliferation of activated lymphocytes secreting high amounts of inflammatory cytokines seems to be the main pathogenesis. The diagnosis of HLH can often be difficult. It may presents in many forms such as fever of unknown origin, hepatitis, acute liver failure, and sepsis-like illness. Here we present a newborn galactosemia case presented with HLH. Close monitoring of the diagnostic criteria of HLH during the course of galactosemia-associated hemophagocytosis, both before and after dietary treatment, should be performed in order to fully determine if the triggering mechanism is infection or accumulation of metabolites. CONFLICT OF INTEREST: None declared.

Portal gastropathy and duodenopathy in children with extrahepatic and intrahepatic portal hypertension: endoscopic diagnosis and histologic scoring.

OBJECTIVES: The aim of the study was to determine the frequency of portal gastropathy (PG) and duodenopathy (PD) in children, to document the correlation of various clinical and laboratory parameters associated with portal hypertensive gastroduodenal lesions, to compare the endoscopic portal hypertensive lesions with different histologic findings, and to evaluate the use of a possible histologic scoring system. METHODS: All children undergoing endoscopic investigation for portal hypertension (PH) between January 2006 and November 2007 were analysed retrospectively. Clinical and demographical data and endoscopic and histologic findings were recorded. Histologic findings suggestive of PG and PD (capillary dilation, increased numbers of capillaries, histologic bleeding, and edema) were scored. RESULTS: Of 51 consecutive children (29 boys, mean age 10.1 ± 3.6 years [range 2.5-15.8 years]), 28 were cirrhotic. PG was diagnosed in 58.8% endoscopically. Children with cirrhotic PH had the highest rate of PG (64.3%), whereas those with extrahepatic or intrahepatic noncirrhotic PH were alike (50% and 54.5%, respectively). Baveno PG scores were higher in children with cirrhosis with higher Child-Pugh scores. Capillary dilation was the only histologic finding showing significant association with the endoscopic diagnosis. Only 9% had PD on endoscopy. None of the histologic findings correlated with endoscopic diagnosis of PD. CONCLUSIONS: PG and PD are seen in children with extrahepatic and intrahepatic PH at rates similar to those reported in adult studies. Baveno PG scores increased in parallel with Child-Pugh class in children with cirrhosis. Capillary dilation was the only histologic finding showing significant association with the endoscopic diagnosis of PG in this study.

Human herpes virus type 8-associated Kaposi sarcoma in a pediatric liver transplant recipient.

Development of KS in pediatric liver transplant recipients is a rare entity and has dismal prognosis. Latent HHV-8 infection, immunosuppression, and genetic predisposition are possible etiological factors. Decreasing the dose or cessation of immunosuppressive drugs, switching to sirolimus with antiproliferative and antitumor properties, and different chemotherapeutic regimens are the current therapeutic strategies. We herein report a pediatric liver transplant recipient who developed generalized KS at post-transplant fifth month. The disease had an aggressive course despite the highly toxic chemotherapy. On the other hand, a prompt and durable response was provided by paclitaxel with tolerable side effects. The patient is now free of disease for at least 24 months and healthy with good graft function under sirolimus therapy as maintenance immunosuppression. Instead of highly toxic chemotherapy, paclitaxel can be used as therapeutic option in cases with generalized disease and in those who are unresponsive to conventional chemotherapy. However, new studies are needed to assess the efficacy of the paclitaxel therapy in KS in the liver transplant recipients.

The role of plasma exchange in acute liver failure of autoimmune etiology.

BACKGROUND: Autoimmune hepatitis (AIH) is characterized by increased immunoglobulin G (IgG) levels, the presence of autoantibodies, and various degrees of lymphocyte predominant inflammation and fibrosis histologically. Immunosuppressive therapy induces remission in approximately 80% of those affected. However, liver transplantation is indicated in patients with acute liver failure with encephalopathy at presentation. Liver supporting systems, including plasma exchange (PE) allow bridging patients to transplantation or spontaneous recovery in the setting of liver failure. The role of these systems has not been assessed in children with liver failure of autoimmune etiology. CASE: Herein, we report three cases of AIH with fulminant presentation, with marked symptom resolution with PE as an adjunct therapeutic option to immunosuppressive treatment. CONCLUSION: In the setting of AIH, PE may have a special therapeutic role by removing autoantibodies and cytokines, therefore preventing further liver damage and decompensation, and allowing time for recovery.

Familial Mediterranean Fever Mutation Analysis in Pediatric Patients With Inflammatory Bowel Disease: A Multicenter Study.

BACKGROUND: The aim of the study was to evaluate familial Mediterranean fever (FMF) mutation analysis in pediatric patients with inflammatory bowel disease (IBD). The relation between MEFV mutations and chronic inflammatory diseases has been reported previously. METHODS: Children with IBD (334 ulcerative colitis (UC), 224 Crohn's disease (CD), 39 indeterminate colitis (IC)) were tested for FMF mutations in this multicenter study. The distribution of mutations according to disease type, histopathological findings, and disease activity indexes was determined. RESULTS: A total of 597 children (mean age: 10.8 ± 4.6 years, M/F: 1.05) with IBD were included in the study. In this study, 41.9% of the patients had FMF mutations. E148Q was the most common mutation in UC and CD, and M694V in IC (30.5%, 34.5%, 47.1%, respectively). There was a significant difference in terms of endoscopic and histopathological findings according to mutation types (homozygous/ heterozygous) in patients with UC (P < .05). There was a statistically significant difference between colonoscopy findings in patients with or without mutations (P = .031, P = .045, respectively). The patients with UC who had mutations had lower Pediatric Ulcerative Colitis Activity Index (PUCAI) scores than the patients without mutations (P = .007). CONCLUSION: Although FMF mutations are unrelated to CD patients, but observed in UC patients with low PUCAI scores, it was established that mutations do not have a high impact on inflammatory response and clinical outcome of the disease.

The role of the non-invasive serum marker FibroTest-ActiTest in the prediction of histological stage of fibrosis and activity in children with naïve chronic hepatitis B infection.

The aim of this study was to investigate whether the non-invasive serum marker FibroTest-ActiTest (FT-AT) reliably predicts the histological stage of fibrosis and/or activity, and decreases the need for a liver biopsy. Twenty-five children with naïve chronic hepatitis B were analyzed for haptoglobin, alpha2-macroglobulin, apolipoprotein A1, bilirubin, gamma-glutamyl transferase, and alanine aminotransferase activity, and the FT-AT scores were computed. FT-AT scores were compared with histological data. FT predicted insignificant fibrosis in 14/23 (61%) patients at a cut-off level of 0.31. Nine patients (36%) had significant histological fibrosis, but none were predicted by FT. There was no correlation between FT scores and histological stage of fibrosis (r: -0.221, p = 0.228). All 4 patients with significant histological activity had corresponding significant activity in AT (100%). Fifteen out of the 19 patients (78.9%) with significant activity in AT had insignificant histological activity. At the cut-off level of 0.36, AT predicted insignificant activity in all 6 patients (100%). There was no correlation between AT scores and histological activity (r: 0.245, p = 0.237). According to histological data, 12 patients were candidates for treatment, but FT-AT did not predict 3 of them (25%). FT-AT does not appear ready for use in detecting either the stage of fibrosis or activity in children with chronic hepatitis B.

Is there a relationship between Helicobacter pylori infection and erosive reflux disease in children?

AIM: The aim of this study was to investigate the relationship between Helicobacter pylori infection and erosive reflux disease in children. METHODS: A total of 206 children [mean age 8.4 +/- 4.9 (0.16-18) years] who underwent diagnostic upper endoscopy were tested for H. pylori infection between 2002 and 2005 and the relationship between H. pylori infection and gastro-oesophageal reflux disease was investigated retrospectively. Endoscopic and histopathological findings were examined retrospectively. When reflux-related oesophageal damage was identified as a result of the histological examination of endoscopic biopsy samples collected from distal oesophagus, the patients were diagnosed with gastro-oesophageal reflux disease and divided into two groups: those with macroscopic erosions or ulceration constituted the erosive oesophagitis group; those without constituted the non-erosive reflux disease group. RESULTS: Prevalence of H. pylori infection was 31.3% in the patients with gastro-oesophageal reflux disease and 36.7% in the control group (p > 0.05). Prevalence of erosive oesophagitis was found to be 23.8% in the patients with H. pylori infection and 41.3% in those without (p > 0.05). CONCLUSION: No negative significant association was found between the prevalence of H. pylori infection and erosive oesophagitis. Presence of H. pylori infection did not influence the severity of oesophagitis either.

Therapeutic management of neonatal chylous ascites: report of a case and review of the literature.

UNLABELLED: Congenital chylous ascites is a rare condition seen in the neonatal period and the data on pathogenesis and treatment modalities are limited. In this article, we report a case of neonate with chylous ascites and review the therapeutic management procedures on chylous ascites in childhood. We present our experience in the diagnosis and treatment of this condition. CONCLUSION: Medium-chain triglycerides (MCT)-based diet can be tried as a first option in chylous ascites treatment. In resistant or unresponsive cases, somatostatin along with TPN can have use in closing the lymphatic leakage or relieving the symptoms effectively and rapidly. Conventional regimens including enteral feeding with MCT-based formula can then be re-administered as a maintenance treatment after reduction of lymph flow with the use of total parenteral nutrition (TPN) and somatostatin infusion combination. Patient-specific approach should be attempted for chylous ascites caused by various disorders and started as soon as possible.

Successful treatment of pediatric post-liver transplant Kaposi`s sarcoma with paclitaxel.

BACKGROUND: Kaposi`s sarcoma (KS) is a complication of immunosuppressive therapy for transplant recipients. Unlike adult recipients, KS in pediatric organ transplantation is quite rare. Treatment is usually withdrawal of immunosuppression; non-responders often receive chemotherapy. CASE: We have reported a child with post-liver transplant visceral KS which has progressed despite withdrawal of immunosuppressive therapy, who has been treated with Paclitaxel for three weeks. KS has regressed completely after four cycles of Paclitaxel. CONCLUSION: Paclitaxel should be considered as an effective first line treatment option for patients with posttransplant KS.

Transient complete atrioventricular block during liver transplantation.

Intraoperative dysrhythmias commonly occur in the surgical management of congenital heart diseases. It may also be seen in other surgical procedures. The initiating factors for an arrhythmia during surgery is usually a transient insult such as hypoxemia, cardiac ischemia, catecholamine excess, electrolyte abnormality and acidosis. CAVB is a life-threatening dysrhythmia in all ages. We herein report a case of transient CAVB in a 30-month-old boy during living-related liver transplantation for bile duct paucity-associated liver cirrhosis. Moreover, we discuss the probable etiology and treatment of CAVB in liver transplantation.

Investigation of impaired carbohydrate metabolism in pediatric liver transplant recipients.

OGTT was performed in 28 liver transplants maintained with tacrolimus to investigate carbohydrate metabolism and assess risk factors for development of PTDM. None had PTDM that was detected by OGTT. Early PTDM in four cases (14.3%) resolved in follow-up. Five new cases (17.9%) demonstrated DCM (DCM = IGT +/- hyperinsulinemia). Fasting measurements were normal in two hyperinsulinemic cases. With one (20%, p > 0.05) exception none of the children with DCM were overweight or had a family history of diabetes. All five (100%) children with DCM had been given high cumulative dosage of steroids 18 (78.3%)--without DCM (p > 0.05). The median age of children with DCM was greater [4.3 (12.7-18.0) vs. 7.0 (2.3-18.0) yr, p < 0.01] and duration of follow-up longer [5.3 (2.3-7.0) vs. 2.5 (0.7-7.3) yr, p < 0.05]. Four children (80%) with DCM were pubertal (p < 0.05). However, neither age nor duration of follow-up or pubertal stage had significant effect on DCM development. Early PTDM is a transient phenomenon and is not predictive for future development of diabetes. DCM is frequently observed in liver transplanted children. Albeit the children with DCM were given high cumulative dose of steroids, were older, mostly were pubertal, and had longer duration of follow-up, we cannot draw firm conclusions on effects of the risk factors on carbohydrate metabolism because of the small sample size and relatively short duration of follow-up. Unlike fasting measurements, OGTT can detect all children with DCM.