Bone mineral density in children with cirrhosis.

BACKGROUND: Despite the clinical importance of osteoporosis in individuals with cirrhosis, little is known about it, especially in children. We evaluated the bone mineral density (BMD) and bone mineral content (BMC) of children with cirrhosis. METHODS: Forty children with cirrhosis (mean age, 10.4 +/- 3.9 years) were involved. BMD and BMC were measured by dual energy X-ray absorptiometry at lumbar vertebrae 1-4, and the results were compared with those of 62 healthy age- and sex-matched children. RESULTS: The mean lumbar spine BMD of patients with cirrhosis was 0.482 +/- 0.107 g/cm(2) and that of the controls was 0.687 +/- 0.172 g/cm(2) (P < 0.0001). The mean lumbar spine BMC of patients with cirrhosis was 20.008 +/- 8.409 g and that of controls was 32.859 +/- 14.665 g (P < 0.0001). After the confounding variables (weight, height, and pubertal stage) were controlled for, the difference in BMD and BMC values between patients with cirrhosis and healthy controls was significant (0.535 +/- 0.061 g/cm(2) vs 0.653 +/- 0.048 g/cm(2), and 24.515 +/- 5.052 g vs 29.952 +/- 3.971 g, respectively). CONCLUSIONS: Because of the significant difference in BMD and BMC values between our patients with cirrhosis and healthy controls, patients with cirrhosis should be evaluated for osteopenia.

The canine copper toxicosis gene MURR1 is not implicated in the pathogenesis of Wilson disease.

BACKGROUND: It has recently been demonstrated that the Wilson disease (WD) protein directly interacts with the human homolog of the MURR1 protein in vitro and in vivo, and that this interaction is specific for the copper transporter. The aim of the present study was to clarify the role of MURR1 in the pathogenesis of WD as well as in other WD-like disorders of hepatic copper metabolism of unknown origin. METHODS: Using the single-strand conformation polymorphism (SSCP) method followed by sequencing, we analyzed the 5' untranslated region (UTR) and three exons of the MURR1 gene in three groups of patients: 19 WD: patients in whom no mutations were detected in the ATP7B gene, 53 WD: patients in whom only one mutation in the ATP7B gene was found, and 34 patients in whom clinical and laboratory data suggested a WD-like disorder of hepatic copper metabolism of unknown origin. RESULTS: We detected in these patients six rare nucleotide substitutions, namely one splice-site consensus sequence and one missense and four silent nucleotide substitutions. All substitutions except one were found in the heterozygous state. No difference in the frequencies of the various substitutions was observed between patients and controls. CONCLUSIONS: These data suggest that the MURR1 gene and its protein product are unlikely to play a primary role in the pathogenesis of Wilson disease. More extensive studies with larger numbers of clinically homogeneous patients should be carried out to establish whether nucleotide alterations in the MURR1 gene may have a role in causing WD or WD-like disorders or act as modifying factors in the phenotype variability in WD.

Chronic hereditary pancreatitis with N29I mutation in a Turkish child.

Hereditary pancreatitis, an autosomal dominant disease, is the second most common cause of pancreatitis in children. Here we report a child with recurrent pancreatitis attacks and N29I mutation. Due to the increased risk of pancreatic cancer, taking a detailed past and family history and early diagnosis are important.

Fanconi-Bickel syndrome in three Turkish patients with different homozygous mutations.

Three Turkish patients with Fanconi-Bickel syndrome are presented. Prominent clinical findings of patients included hepatomegaly, growth retardation, hypoglycemia, characteristic tubular nephropathy, and rickets. Each patient had a different homozygous mutation of glucose transporter 2 (GLUT2) gene.

Does simultaneous gastric and esophageal pH monitoring increase the diagnosis of gastroesophageal reflux disease?

The duration of gastric acidity may affect the interpretation of esophageal pH monitoring study. The aim of this study was to increase the sensitivity of pH monitoring by simultaneous gastric and esophageal pH recording. Fifty-seven patients were enrolled in the study. After the first analysis, the recording periods in which gastric pH was >4 were excluded and after this exclusion parameters were recalculated. Of the 57 patients, 14 (24.6%) (mean age, 70+/-4.6 years) were diagnosed as having gastroesophageal reflux disease with the use of conventional method. After correction, gastroesophageal reflux disease diagnosis was made in 6 additional patients (mean age, 2.4+/-2.4 years) and total number of patients with reflux increased to 20 (35.1%) (p=0.031). The mean percentage time of gastric pH>4 was significantly greater in children younger than 2 years of age than that in those older than 2 years of age (50.6%+/-15.2% vs 33.7%+/-18.1%) (p=0.001). Exclusion of periods in which gastric pH>4 affected the results more obviously in patients younger than 2 years. Simultaneous gastric and esophageal pH monitoring is useful for the diagnosis of gastroesophageal reflux disease, particularly in children younger than 2 years of age.

Inflammatory bowel disease-like colitis in a young Turkish child with glycogen storage disease type 1b and elevated platelet count.

Inflammatory bowel disease (IBD)-like colitis is a known entity in glycogen storage disease (GSD) type 1b patients. The mean age of the reported cases with IBD-like colitis was 12 +/- 5 years, and all had absolute neutrophil count (ANC) less than 1,000 cells/microl. We report a three-year-old girl with GSD type 1b that was dignosed by mutation analysis. The patient was hospitalized with fever, diarrhea, and perioral and anal ulcers. Colonoscopy was performed and IBD-like colitis was diagnosed. The patient had elevated platelet count beyond the age of three months, but IBD-like colitis was diagnosed at three years of age. An elevated platelet count may be a warning sign for the IBD-like colitis in young patients with GSD type 1b.

Interferon-alpha and lamivudine combination therapy of children with chronic hepatitis b infection who were interferon-alpha nonresponders.

Greater than one-half of children with chronic hepatitis B infection are nonresponders to interferon-alpha (IFN-alpha). The aim of this study was to investigate the efficacy of lamivudine (LMV) and IFN-alpha combination therapy in these children. Nineteen children were given LMV alone for 3 months; then IFN-alpha was added to LMV for 6 months. Virologic response was achieved in seven (36.8%) patients. LMV and IFN-alpha combination therapy may represent an effective treatment option.

The cagA status of Helicobacter pylori isolates from dyspeptic children in Turkey.

There are inconsistent reports regarding cytotoxin-associated gene A (cagA) status of Helicobacter pylori isolates and the severity of the mucosal lesions in children. The aim of this study was to determine the prevalence of cagA(+) strains and to evaluate its correlation with clinic and endoscopic findings. We examined 45 H. pylori strains that were grown on brain-heart infusion agar supplemented with 7% horse blood. Following 72 h of incubation colonies were harvested and bacterial DNA was extracted. Polymerase chain reaction primers F1 and B1 were used to amplify a 348-bp internal fragment of cagA. The prevalence of cagA in Turkish pediatric patients was 55.6%. No association was found between cagA status and the severity of gastro-duodenal lesions.

Serum carnitine and selenium levels in children with celiac disease.

BACKGROUND AND AIM: Celiac disease (CD) is a gluten-induced enteropathy that results in malabsorption of nutrients. We studied the serum levels of carnitine and selenium in children with CD. METHODS: Serum levels of free carnitine and selenium were studied in 30 children (mean age 8.1 [4.4] years) with CD and 30 age- and gender-matched healthy children. All patients had type 3 duodenal lesions. The mean (SD) serum levels of free carnitine and selenium were lower among patients with CD (24.5 [7.7] micromol/mL and 52.1 (12.9) micromol/mL, respectively) than among healthy controls (29.4 [9.2] and 65.1 [17.2] micromol/mL; p < 0.05 each). Levels were similar in children with and without diarrhea. CONCLUSIONS: Serum carnitine and selenium levels are decreased in children with CD, probably due to malabsorption.

Serum hyaluronic acid concentrations in children with cirrhosis.

BACKGROUND: Liver disease is associated with increased levels of hyaluronic acid (HA). AIM: To evaluate serum HA concentrations in children with cirrhosis and its relation with liver function tests and Child-Pugh score. METHODS: Twenty-two children with biopsy-proven liver cirrhosis were studied. All were assessed for the presence of ascites or encephalopathy and liver function tests were performed. Patients were categorized according to Child-Pugh criteria. Serum HA was measured using microELISA (normal 0-100 ng/mL). Twenty-two children with chronic hepatitis B and no cirrhosis were studied as controls. RESULTS: Serum HA level in the cirrhotic children was 85.2 (72.8) ng/mL; levels were high (166.0 [46.3] ng/mL; range 115-246) in 8 (36.4%) patients. Three of 11 (27.2%) Child-Pugh class A patients, 3 of 8 (37.5%) class B patients, and 2 of 3 (66.7%) class C patients had elevated serum HA values (p=ns). Serum HA levels correlated with direct bilirubin level. The control group had lower levels (4.8 [2.3] ng/mL; p< 0.05), which were in the normal range. CONCLUSION: Serum HA level may be useful as a diagnostic tool in children with cirrhosis.

Evaluation of diagnostic parameters of Wilson's disease in childhood.

BACKGROUND: Wilson's disease (WD) is an autosomal recessive disorder with variable clinical presentation. Its diagnosis depends on a combination of clinical and laboratory findings. We evaluated the sensitivity of various diagnostic tests in children with WD and high liver copper concentrations. METHODS: Thirty-three children (6-15 years old, 19 male) with confirmed WD (hepatic copper >250 mcirog/g dry weight) were evaluated retrospectively. Eyes were examined with biomicroscope for Kayser-Fleischer rings and urinary copper content was determined in 30 patients. Serum ceruloplasmin levels were measured and liver tissue samples were stained with orcein in all. RESULTS: All patients presented with hepatic disease. Four patients also had neurological involvement. Hepatic copper concentration was between 250 and 1200 microg/g. Eighteen patients had liver cirrhosis, 9 chronic hepatitis, and 6 had massive hepatic necrosis on liver biopsy or necropsy. The sensitivity of various tests evaluated was: 100% (30/30) for urinary copper excretion, 88% (29/33) for orcein staining on liver tissues, 82% (27/33) for ceruloplasmin levels, and 63% (19/30) for presence of Kayser-Fleischer ring. Kayser-Fleischer ring was present in all patients with neurological manifestations and in 58% of patients with only hepatic presentation. CONCLUSIONS: 24-hour urinary copper excretion seems to be the most sensitive test for diagnosis of WD, particularly when liver biopsy cannot be performed due to coagulation abnormalities.

TTV infection in children with and without liver disease.

BACKGROUND: TTV DNA has been reported in patients with a broad spectrum of hepatic disorders as well as in healthy people. AIM: To clarify the role of TTV in children with liver disease and in healthy children. METHODS: Degenerate primers designed to amplify a target sequence from the ORF 1 region of TTV genome were used for nested PCR, to detect TTV DNA in sera. RESULTS: TTV was detected in 3 of 18 children with chronic hepatitis B (16.7%), 2 of 17 hepatitis B carriers (11.8%), 2 of 17 children with cryptogenic chronic liver disease (11.8%), and 1 of 40 (2.5%) children without liver disease. The infection rate was similar among the various study groups and in the various age groups. There was no difference between TTV positive and negative children in respect to gender, history of surgery, parenteral treatment, transfusion of blood and blood products, presence of hepatomegaly, splenomegaly, jaundice, and transaminase values. CONCLUSION: TTV does not seem to have an etiologic role in cryptogenic liver disease in children and does not seem to influence the clinical course of liver disease.

Hemophagocytic syndrome associated with visceral leishmaniasis.

Hemophagocytosis, either primary (familial) or secondary (reactive), is a life threatening condition in childhood. Etiology should be vigorously searched to avoid a diagnosis of primary hemophagocytosis and treatment with cytotoxic drugs. A child with visceral leishmaniasis causing hemophagocytosis is presented.

Lamivudine and high-dose interferon-alpha combination therapy for naive children with chronic hepatitis B infection.

BACKGROUND: More than half of the children with chronic hepatitis B infection are nonresponders to interferon-alpha. The aim of this study was to investigate the efficacy of lamivudine and interferon-alpha combination therapy after a 3-month lamivudine induction in children with chronic hepatitis B. STUDY: Twenty naive children were given lamivudine (4 mg/kg per day; maximum, 100 mg) alone for 3 months; then interferon-alpha (10 MU/m, thrice weekly) was added to lamivudine for 6 months. After interferon-alpha was stopped, lamivudine alone was continued for 6 months. Therapy was stopped 6 months after HBeAg seroconversion. Every 3 months, HBV markers were studied and virologic response was defined as HBV DNA negativity, and HBeAg loss with AntiHBe seroconversion. RESULTS: At the end of 15 months, virologic response was achieved in 11 (55%) of patients and 12 patients (60%) cleared hepatitis B e antigen. Therapy was well tolerated. CONCLUSION: Preliminary results of our study seem to indicate that lamivudine and high-dose interferon-alpha combination therapy after a 3-month lamivudine induction may represent an effective treatment option for children with chronic hepatitis B.

Cirrhosis in children with celiac disease.

BACKGROUND: Liver involvement represents an extra-intestinal feature of celiac disease (CD) and shows a clinical spectrum varying from nonspecific reactive hepatitis to cirrhosis. Here we report the association of cirrhosis with CD in 5 children. PATIENTS AND METHODS: The mean age of the patients was 9.4 +/- 2.8 years. Viral, metabolic, and autoimmune etiology of liver disease was ruled out. Intestinal and liver biopsies were performed to confirm the histologic diagnosis in all subjects. RESULTS: Three of the patients had chronic diarrhea and hepatosplenomegaly in whom diagnoses of CD and cirrhosis were established at presentation simultaneously. In the other 2 patients, CD was diagnosed following an initial diagnosis of cirrhosis. At diagnosis, alanine aminotransferase (range, 64-271 IU/L) and aspartate aminotransferase (range, 90-225 IU/L) values were elevated. After 1 to 5 years of a gluten-free diet (GFD), normalization of serum aminotransferase levels and clinical improvement were observed in 3 patients with strict GFD. The other 2 patients without improvement of the liver disease had poor dietary compliance. CONCLUSION: CD may be associated with severe hepatic damage in children and strict GFD may have beneficial effect on the course of liver disease. Serologic screening of CD should be included in differential diagnosis of chronic liver disease of unknown origin.

Histologic features of the liver in type Ia glycogen storage disease: comparative study between different age groups and consecutive biopsies.

In this report, the histologic criteria for the diagnosis of type Ia glycogen storage disease (GSD) in a wide age range were studied. Liver needle biopsies of 44 patients with type Ia GSD confirmed by enzyme analysis were re-evaluated and compared. Fatty change, nuclear hyperglycogenation (NH), and fibrosis were examined and graded. The second biopsies of 14 patients were also evaluated and compared with the first ones. The patients were grouped according to age: group I: <1 year (18 cases), group II: 1-5 years (19 cases), group III: >5 years (7 cases). A mosaic pattern was detected in all biopsies. The amount of fibrosis in group I was less than that in the other two groups. The fatty change in group I was more prominent. There was not much difference in the amount of NH between age groups. In comparing the two different biopsies of 14 patients, the amount of fibrosis was found to be increased in 7 cases. NH was also increased in a different group of 7 patients. These findings were both statistically significant. The amount of fatty change was minimal in most of the cases. Fibrosis is associated with types III, IV, VI, IX, and X GSD. Our results support previous studies stating that fibrosis may also be present and varies in extent in type I GSD. Fatty change as large lipid vacuoles and NH may not be seen in many cases of type I GSD. Therefore, histologic criteria for the diagnosis of GSD may not be specific, and enzyme analysis should be performed.

Extrahepatic portal vein thrombosis in children: etiology and long-term follow-up.

OBJECTIVE: Mortality of extrahepatic portal vein thrombosis depends on underlying causes other than gastrointestinal bleeding. The aim of this study was to evaluate the etiology, treatment, and prognosis of patients with extrahepatic portal vein thrombosis. METHODS: The records of 12 patients (age range: 1-9 years) diagnosed with extrahepatic portal vein thrombosis with a minimum follow-up of 2 years were analyzed retrospectively. Their diagnostic evaluations, treatment modalities, complications and long-term follow-ups were noted. RESULTS: Mean follow-up period was 7.4 +/- 3.9 years (2-14 years). Hemorrhage from esophageal varices was the prevalent symptom in 6 patients (50%). Six patients had signs of hypersplenism, 5 were found to have thrombophilia: 2 protein C, 1 protein S, 1 combined protein S, C, and antithrombin III deficiency, and 1 homozygous factor V Leiden mutation. Two patients had congenital cardiovascular abnormalities, and 1 patient developed portal thrombosis after splenectomy operation. None of the patients who started propranolol prophylaxis before first bleeding episode bled during their follow-up periods. Endoscopic sclerotherapy succeed in 66.6% variceal hemorrhages. Shunt surgery was performed in 1 patient. The patients neither faced a life-threatening variceal bleeding nor died during follow-up period. CONCLUSION: Prognosis of extrahepatic portal vein thrombosis is good in childhood. Thrombophilic states are the most frequent precipitating causes. Propranolol for prophylaxis of variceal bleeding and sclerotherapy might be the preferred modalities.