[show abstract][hide abstract] ABSTRACT: Wilson's disease (WD) is a progressive degeneration of hepatolenticular tissue caused by excessive tissue-damaging copper accumulation and in which liver involvement most frequently presents in childhood. Neurological signs also accompany liver disease with time. However, subclinical neurological involvement may occur earlier and diagnostic methods that reveal this subclinical involvement are not well established. The aim of the current study is to assess the subclinical neurological involvement by using multimodality evoked potential (EP) measurements and to explore the relationship between neurological disease and the severity of liver damage.
The patient group included 28 children (mean age 11.8 ± 2.9 years, range 5.5-17) diagnosed with WD and a control group included 24 age-matched healthy children. Multimodality EP tests (Nihon Kohden Neuropack 8 4200K) of both groups were performed at the Department of Neurology Electrophysiology Laboratory of Ege University.
At least one abnormal EP value was observed in 53.5% of the children in the patient group. At least on one side, there were abnormal values for visual evoked potential (VEP) P100, brainstem auditory evoked potential (BAEP) and somatosensory evoked potential (SEP), where the ratios were 25, 28.5, and 11%, respectively. Absolute latency values of patients with right-side VEP P100 and left-side BAEP I, and the interpeak latency values of right-side BAEP I-III were significantly high. The difference in right-side BAEP I-III interpeak latency between cirrhotic and noncirrhotic groups was found to be statistically significant (P<0.05).
The EP examinations can be an indicator of subclinical brain damage in non-neurological WD; however, cirrhosis because of WD does not cause an increase in the EP values. Detection of changes in the EP values periodically, especially at the time of diagnosis and during the treatment follow-up, may be valuable for revealing subclinical impairment.
European journal of gastroenterology & hepatology 03/2012; 24(6):627-32. · 1.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: we aimed to analyze clinical and inflammatory markers of steroid non-response in patients with moderate/severe ulcerative colitis (UC) at the time of diagnosis.
this study included patients who were graded as having moderate/severe UC and received corticosteroids as first-line therapy. Demographic, clinical and laboratory findings and pediatric ulcerative colitis activity scores (PUCAS) were recorded. Response to corticosteroids was assessed 30 days after the induction and long-term therapy.
twenty-eight children were diagnosed as having moderate/severe UC. Their mean age ± SD was 1 2.2 ± 4 years, and 17% were under 5 years of age. PUCAS at their initial admission was 56.9 ± 11.8. UC was observed at the left colon in 9 patients (32.1%), and pancolitis in 19 (67.9%). At the end of the 30th day, UC was completely remitted in 15 patients (53.5%), partially remitted in 2 (7.1%), and no response in 11 (39.2%). Short-term follow-up showed partial remission in 2 patients, and overall remission with steroid in 17 (60.7%). Non-responders were given second-line treatment; steroid dependency was documented in 2 patients (7.1%) and another 2 (7.1%) patients underwent colectomy. Predictors for steroid non-response were analyzed and only PUCAS at the initial admission was found to be associated with non-response to steroids (51.4 ± 11.4 vs. 65.4 ± 6.8, P<0.05).
approximately half of the pediatric patients had complete response to steroid therapy in a long period. PUCAS could be used as a potential marker of "failed response" to steroid, but should be supported with a number of prospective randomized controlled studies.
World Journal of Pediatrics 02/2011; 7(1):50-3. · 1.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Autoimmune hemolytic anemia with giant cell hepatitis is a distinct entity in children. It is usually fatal with progressive liver disease. Immunosuppressive treatment with conventional drugs offers some response; however, it is usually only temporary. Alternative therapeutic options with monoclonals have been reported with promising remission of the disease. We report a case with autoimmune hemolytic anemia+giant cell hepatitis after varicella infection. She was resistant to standard immunosuppressive combinations, and rescue therapy with rituximab was used. Remission was not achieved with the drug and the child died with septic complication.
The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology 12/2010; 21(4):448-51. · 0.48 Impact Factor
[show abstract][hide abstract] ABSTRACT: Host-related immune factors in childhood chronic hepatitis B and change in the initial profile with interferon (IFN)-α treatment need to be clarified.
Sixteen patients were included in the study, and 10 million units of IFN-α treatment 3 times per week for 6 months was initiated. Pre- and post-treatment percentages of interleukin (IL)-2 and IFN-γ in CD4+ T cells were assessed to determine intracellular T helper cell 1 (Th1) type cytokine expression. Similarly, percentages of intracellular IL-2 and IFN-γ were detected to verify cytotoxic T cell 1 (Tc1) type cytokine expression in CD8+ T cells. Percentages of Th2 and Tc2 type cytokine expression (IL-4 and IL-13) were determined in CD4+ and CD8+ T cells, respectively.
Six (50%) of these were evaluated as having no response and the other half with partial/complete response. All patients had higher percentages of Th2 cells with respect to healthy controls pre-treatment. Tc percentages, both Tc1 and Tc2, were significantly different between these groups, being higher in the patient group. When values of the nonresponder group were compared with healthy controls, IL-4 expression was higher and the percentages of Th1 type cells were significantly low. IL13 expression in Th and Tc cells decreased after 6 months of treatment in the unresponsive group. The decrease we observed in Th1 percentages with treatment, in the responsive group, may be due to Th1 deposition shifting from the periphery to liver tissue, as reported before. Intracellular cytokine profiles of treatment responders and normal controls were not different.
This is the first study in children comparing baseline and post-treatment intracellular cytokine profiles with values in healthy controls.
The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology 12/2010; 21(4):401-10. · 0.48 Impact Factor
[show abstract][hide abstract] ABSTRACT: Familial Mediterranean fever (FMF) is hereditary episodic febrile syndrome characterized by acute attacks of fever and serosal inflammation, generally lasting 1-3 days and resolves spontaneously. Apart from abdominal pain, patients may present with variety of abdominal manifestations such as acute peritonitis, mechanical intestinal obstruction, diarrhea, bowel infarction, amyloidosis and small amounts of peritoneal fluid during the acute attacks. A 6-year-old boy was admitted with massive ascites. After extensive laboratory investigations, no causative agent could be identified. On subsequent days, he developed fever and skin eruptions. Acute-phase reactants were increased. A second tomography revealed cystic fluid collection near the anterior side of spleen that invades the stomach. An exploratory was performed and histopathological examination of the all resected specimens revealed mix inflammatory cell infiltrate associated with severe myofibroblast proliferation suggesting chronic inflammatory process on the mesenteric region. A diagnosis of FMF was suspected based on the clinical, laboratory and histopathological findings, and a trial of colchicine therapy initiated. Ascites and other serosal inflammations improved within 1 week without any recurrence during the next 12-month period on colchicine treatment. Atypical presentations of FMF have been increasingly reported. Pediatricians should keep FMF in mind in the differential diagnosis of massive ascites especially in regions where hereditary inflammatory disease are common.
Rheumatology International 06/2009; 30(4):531-4. · 2.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: We analyzed infections that occurred within one month prior to LT, identified factors associated with their occurrence and effect of infections on post-transplant mortality. The study group included 40 consecutive children who underwent LT. Sites and types of infection and culture results were recorded prospectively. IID was assessed. Risk factors for the infectious events were analyzed. Forty infection episodes were found in 24 patients (60%); 90% were bacterial, 7.5% fungal, and 2.5% viral. Overall, IID was 38.2 per 1000 patient days. Sites of bacterial infection were urinary tract in 13 events (36.1%) and blood stream in 11 events (30.5%). Bacteremia (culture positive infection episodes) was identified in 19 events (52.7%). Gram-negative isolates were twice as frequent as Gram-positive infections (63.1% vs. 36.9%). Risk factors for the infectious complications were young age, low body weight, prior abdominal surgery, chronic liver disease related to biliary problems, presence of ascites, portal hypertension and cirrhosis, and high PELD score (p < 0.05 for all). Infectious complications in pediatric LT candidates are common. Preventive measures are important not only to reduce the infectious complications but also to prevent the post-operative mortality.
[show abstract][hide abstract] ABSTRACT: We sought to analyze the long-term growth in children with celiac disease (CD) as well as the association of height and weight SD score at the end of 4 years with the demographic and clinical presentation at initial admission. Thirty-four children with CD were enrolled in the study and followed for at least 4 years. Patients were divided into three groups (Group 1: patients <or=5 years old, Group 2: patients 5-10 years old, and Group 3: patients >10 years, at the time of diagnosis). Patients' charts were reviewed for demographic and clinical features at initial admission. Anthropometric measurements at initial admission, at 6th months, and 1st, 2nd, 3rd, and 4th years were recorded. Gluten-free diet led to rapid increase in weight SD and height SD score in patients <or=5 years old at the time of diagnosis (Group 1). Increment in height SD score was the highest in patients 5-10 years old (Group 2) at the end of 4 years. A negative correlation was found between age at the time of diagnosis and weight and height SD score at the end of 4 years (r = -0.503, P = 0.03 and r = -0.554, P = 0.01). Multiple regression analysis revealed that height SD score at the end of the 4 years was associated with age at the time of diagnosis. The other factors had no effect on the weight and height SD score at the end of 4 years. Early diagnosis and good adhesion to a gluten-free diet are essential for long-term growth in CD. Celiac societies and the mass media must expand an effort to educate the community regarding the symptoms of the disease.
Digestive Diseases and Sciences 01/2009; 54(10):2183-7. · 2.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: Inflammation is an important feature of biliary atresia, and recent studies suggest that its occurs in a genetically susceptible host. The intercellular adhesion molecule-1 (ICAM-1) is of paramount importance for the initiation and propagation of various inflammatory conditions.
To determine whether the Glu241Arg polymorphism in the ICAM-1 gene, which impairs inflammatory responses, is associated with biliary atresia.
Between February 2002 and November 2004, 19 patients (mean age 1 +/- 0.4 years) diagnosed as biliary atresia were included in the study. Thirty-eight children with chronic liver disease and a group of unrelated healthy controls (n = 123) included in this study. After informed consent, blood was collected and genomic DNA was obtained. Genotyping was performed by amplification-refractory mutation system polymerase chain reaction (ARMSPCR). Associations were assessed by using Fischer's exact test.
ICAM G242R A allele frequency was significantly higher in the BA group than in both the CLD and healthy control groups (OR = 4.4, 95 CI% 1.3-15.1, P = 0.03 and OR = 4.8 CI% 1.5-15.6, P = 0.01, respectively). Univariate analysis showed that polymorphism of ICAM G241R polymorphism was significantly related to biliary atresia. There was not significant correlation between PELD score and ICAM-1 genotypes both in BA and CLD groups.
These findings provide evidence for the possible role of ICAM-1 241R polymorphism in BA pathogenesis.
Digestive Diseases and Sciences 08/2008; 53(7):2000-4. · 2.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: Prolonged QTc interval (>440 ms) is a common abnormality in adult patients with CLD and has been reported to predict patient survival. In this study, 88 children who underwent evaluation for LT, including a 12-lead electrocardiogram and echocardiogram included to determine the frequency of QTc prolongation and related factors in children with CLD and the effect of LT on these factors. Sixty-nine healthy, age- and sex-matched children served as controls. QTc interval was prolonged in 40 CLD patients (45.4%). It was found to be related to PELD score and presence of portal hypertension. Mean QTc was higher in patients who died prior to LT than in the survivors without LT. Mortality risk was increased 3.66-fold in patients with prolonged QTc (p = 0.001, 95% CI: 2-7.2). Cox regression analysis showed that only PELD score was an independent predictor of survival (p = 0.001, beta = -0.41, 95% CI: 5.58-1.82). Five of 48 transplanted children died within three months post-transplant; QTc was not related to post-transplant survival (p = 0.27). QTc normalized in 63.8% patients after LT. After LT, LAD, LVEF, and LVPWT decreased. In conclusion, QTc prolongation is common in children with CLD and associated with high mortality. It may be useful for assessment of the severity of CLD and for the timing for transplantation.
[show abstract][hide abstract] ABSTRACT: The hepatopulmonary syndrome (HPS) is characterized as a triad: liver disease, intrapulmonary vascular dilatation, and arterial hypoxemia. The aim of this study is to analyze outcome of children with HPS in liver transplant era.
Between September 1996 and November 2006, 172 cirrhotic patients (median age 5 years; range 0.2-22 years, M/F; 97/75) were followed at Ege University Pediatric Gastroenterology, Hepatology and Nutrition Unit. All patients were evaluated by chest radiography, arterial blood gas analysis, and alveolar-arterial oxygen tension difference, contrast echocardiography (CEE) after and before the liver transplantation.
HPS was diagnosed in 33 patients (19%) by CEE. None of them had pulmonary hypertension. HPS was not found related to etiology of the liver disease. Portal hypertension was found related to the development of HPS (75.7% in patients with HPS and 54.6% in others, p = 0.02). 17 of 33 patients with HPS underwent liver transplantation. Preoperative and postoperative period of these patients was uneventful. Patients were extubated in the operating room except for two. Median follow up of transplanted children was 1.9 year (range; 0.75-10 years). Arterial blood gas analysis and CEE positivity regressed in all of them by postoperative 6th month.
HPS is a serious and important complication of cirrhotic children that leads to tissue hypoxia and central cyanosis. HPS seems reversible after liver transplantation in all patients.
[show abstract][hide abstract] ABSTRACT: To analyze the prevalence of Helicobacter pylori (H. pylori) infection in children with celiac disease (CD) and to examine the role of H. pylori infection in clinical, laboratory and histopathological presentations of CD.
Data on 96 children with CD and 235 children who underwent endoscopy were compared for the prevalence and gastric histology pattern of H. pylori. Clinical presentation, laboratory and histological findings of CD children with and without H. pylori infection were compared.
Twenty-one subjects (21.8%) in the CD group and 56 subjects (23.8%) in the control group had H. pylori gastritis. Gastric metaplasia is higher in CD patients with H. pylori gastritis (19%) than in patients without H. pylori gastritis (1.3%) and in the control group (3.5%) (p<0.05 for all groups). Abdominal distension is more common at initial admission in CD patients with H. pylori gastritis (57.1% versus 14.6%, p<0.05). No significant difference was found between H. pylori (+) and (-) CD patients in terms of prevalence of anemia, iron deficiency and iron-deficiency anemia. Only mild duodenal histological findings were more common in H. pylori patients (57.1% versus 26.7%, p<0.05).
CD may be associated with H. pylori gastritis, but it does not affect the clinical presentation of the disease, except for abdominal distension; CD is associated with mild duodenal lesions. A gluten-free diet improves the symptoms in all patients independently of the presence of H. pylori gastritis. Gastric metaplasia increases in the presence of H. pylori gastritis. Further prospective studies are needed to examine the clinical and histopathological outcomes of gastric metaplasia associated with H. pylori gastritis in CD patients.
Scandinavian journal of gastroenterology 05/2008; 43(9):1088-93. · 2.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: We constructed a study to determine the association of anthropometric measurements, biochemical parameters and bone mineral content with nutritional status in infants with neonatal cholestasis.
The study included 38 children with neonatal cholestasis. Nutritional status was assessed by Waterlow criteria, and anthropometric measurements, biochemical parameters and bone mineral content were correlated with the nutritional status at initial admission and at the end of 2 months after nutritional support.
We found that the prevalence of acute and chronic malnutrition was 34.2% and 39.4% in infants with neonatal cholestasis, respectively. No significant difference was found in triceps skinfold thickness (TST), scapular skinfold thickness (SST) and suprailiac skinfold thickness (SuST), arm fat area (AFA) and arm area (AA) among the groups. Mid-arm circumference (MAC), arm muscle circumference (AMC) and arm muscle area (AMA) were significantly lower in patients with chronic malnutrition than both acute malnutrition and patients without malnutrition. MAC was the most reliable marker for the assessment of malnutrition and had the highest positive predictive value (PPV) (80.6%), sensitivity (89.2%) and negative predictive value (NPV) (57.1%). Prealbumin levels were significantly lower in patients with chronic malnutrition than the patients without malnutrition. Increment in MAC and AMC were significantly high in the three groups after 2 months.
MAC is a good indicator of malnutrition in neonatal cholestasis and may also be used for the monitoring of nutritional support; prealbumin may be used for assessment of the severity of malnutrition.
Digestive Diseases and Sciences 04/2008; 53(3):803-8. · 2.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: To report the successful percutaneous transcatheter removal of a snapped intracardiac fragment of the central vein catheter in an infant.
A 3-month-old infant with short bowel syndrome who required long-term parenteral nutrition via portacath central catheter was hospitalized. Two months after the insertion of the second catheter, the distal tip of the catheter snapped and became tangled in the heart. The catheter fragment was removed by a percutaneous femoral vein approach using a 10-mm diameter snare-loop catheter (Amplatz). The procedure was performed under fluoroscopy; the fragment was removed after being released into the right ventricle by pulling the proximal tip with a pigtail catheter. No complications were observed and the patient was transported back to the intensive unit in stable condition.
Central catheter-related complications may cause difficulties in patients with short bowel syndrome prior to intestinal transplantation. The percutaneous retrieval of the fragmented catheter using a snare-loop catheter is a safe and reliable technique and may be used instead of surgery especially in small infants.
Medical Principles and Practice 01/2008; 17(4):343-5. · 0.96 Impact Factor
[show abstract][hide abstract] ABSTRACT: Because clinically evident manifestations are frequent in adults with celiac disease (CD), we aimed to investigate whether early neurological abnormalities may be detected in children with CD.
Electroencephalography, electromyography, and somatosensory evoked potentials were performed in children with CD receiving a gluten-free diet.
The neurophysiological tests revealed subclinical neurological abnormalities associated with CD in 3 (11%) of 27 children: 2 had peripheral polyneuropathy documented with electromyography, and 1 had prolonged latencies in somatosensory evoked potential. Magnetic resonance imaging showed abnormalities in 2 (7.4%) of children: pontine demyelinization in 1 and cortical atrophy in the other.
Because the rate of neurological problems is increased in children with CD, neurological abnormalities should be carefully investigated early after the diagnosis of CD is made.
Journal of pediatric gastroenterology and nutrition 10/2007; 45(3):366-9. · 2.18 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate in vitro T lymphocyte proliferation and specific antibody response to hepatitis B vaccination in two groups of rats fed with normal and marginal zinc content.
Twenty-two Wistar-Albino rats were randomly assigned into two groups and were fed with constant diet. Zinc was suplemented 10mg/kg dry weight in group I (marginal zinc content) (n=14) and 30mg/kg dry weight in group II (n=8). Hepatitis B vaccine (Engerix B, 4mug) was administered intramuscularly after 8 weeks on feeding and a booster dose was applied 4 weeks after the first injection. Rats were killed 3 weeks after the second injection. Peripheral blood mononuclear cells were stimulated in vitro by PHA (2.5mug/ml) and hepatitis B surface antigen (2.5, 5, 10mug/ml). Proliferation was evaluated by ELISA (celltiter-96 aqueous one solution cell proliferation assay). Serum zinc, anti-HBs titer and zinc per dry liver weight were also measured. Two groups were compared with respect to antigen specific antibody and lymphocyte proliferation responses. Proliferation response to HbsAg were expressed as net percent increase (pci) in lymphocyte proliferation from the baseline activity.
Rats' mean body weight and weight gain per month were similar. Median serum zinc was 39 (23-75) and 76(64-115)mug/dl of groups I and II rats, respectively (p<0.05), while there was no difference in liver zinc content between the two groups (37mug/g dry weight versus 32mug/g dry weight). Median anti-HBs levels of groups I and II were 741 (0-10,000)IU/l, 5791 (558-10,000)IU/l, respectively (p<0.05). In lymphocyte proliferation assays, mean net pci with HbsAg of 5 and 10mug/ml were 9.4% and 11.3% in group I rats; while they were 25.3% and 26.1% in group II rats (p<0.01 and p<0.01, respectively).
In vitro cell-mediated immune response and in vivo specific antibody response to hepatitis B vaccine was decreased in rats fed a diet with marginal zinc content. These observations have shown that marginal Zn deficiency might influence the efficacy of hepatitis B vaccination in humans.
Hepatology Research 06/2006; 35(1):26-30. · 2.07 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hepatocellular carcinoma (HCC) is primarily observed in the older children and in most cases it develops in association with liver cirrhosis. Liver transplantation offers a good chance for long-term cure. To evaluate the outcome of children with HCC and the impact of living-donor orthotopic liver transplantation (OLT) on survival a retrospective review of radiographic, laboratory, pathologic, and therapeutic data in 13 children (six female and seven male) with chronic liver disease accompanied with HCC were studied. The patients were divided into two groups according to therapeutic modality: transplanted and non-transplanted patients. Kaplan-Meier survival curves in various therapeutic groups were plotted. The mean age of patients was 6.4 +/- 4.8 yr. Pediatric end-stage liver disease score was adapted to model for end-stage liver disease score for HCC and ranged between 1-44 and 18-44, respectively. The underlying liver diseases were tyrosinemia type 1 (n = 6), chronic hepatitis B infection (n = 6), glycogen storage disease type 1 (n = 1). Alfa-feto protein levels were elevated in all patients except one. Median number of tumor nodules was three (1-10), median maximal diameter of tumor nodules was 3.4 cm (0.5-8). Eleven patients were eligible for OLT whereas two patients were not eligible. Seven of the 11 patients considered for transplantation underwent living-donor OLT. Remaining four patients died while waiting on cadaveric transplant list. Overall 1 and 4-yr survival rates for all patients were 53.3 and 26.6%, respectively, and were found significantly higher in transplanted children than non-transplanted children (72%, 72% vs. 33% and 16.6%). No patient had tumor recurrence at median of 36-month follow-up after OLT. OLT is a life-saving procedure for children with chronic liver disease accompanying with HCC. Living-donor OLT avoids the risk of tumor progression and transplant ineligibility in these children.