Rivka Shapiro

Primary hyperoxaluria type 1 : Improved outcome with timely liver transplantation : A single-center report of 36 children

Background. The appropriate use of liver transplantation in children with type-1 primary hyperoxaluria (PH-1) is not well established. We reviewed our experience with 36 children with PH-1, including 12 who underwent liver transplantation. Patients and Methods. From 1989–1998, 36 children from 10 families in northern Israel were diagnosed with PH-1. Eight children presented with renal failure; seven of these eight had the severe infantile form of the disease. One child was treated with kidney transplantation alone. Combined liver-kidney transplantation has been performed in nine children and preemptive liver transplantation in three children. A review of the patients’ charts for the following parameters was performed: age, clinical signs, and renal sonographic findings at diagnosis, age at onset of dialysis, and current status. Type of transplant, pre- and posttransplant urine oxalate excretion, current renal function, survival, and complications were recorded in liver recipients. Results. Of the 23 nontransplanted children, 9 died of complications related to severe systemic oxalosis and 14 are alive (mean follow-up, 7.4 years), including 2 who are candidates for transplantation. The child who underwent only kidney transplantation died of unrelated causes. Of the 12 liver recipients, 2 died within the first 3 months posttransplant and another child underwent retransplantation due to hepatic arterial thrombosis. At intervals after transplant ranging from 6–54 months, 10 recipients are alive (7 of the 9 recipients of combined liver-kidney transplants and all 3 recipients of preemptive liver transplants). Mean GFR in the 10 survivors is 77 ml/min/m2. In 9 of these 10, daily urinary oxalate excretion normalized. Renal function has improved (mean GFR 86 vs. 58 ml/min/m2) but renal oxalate deposits remain in the three recipients of isolated liver grafts. Conclusions. Our decade-long experience with children with PH-1 supports strategies for early diagnosis and timely liver transplantation. Preemptive isolated liver transplantation should be considered in children who develop the disease during infancy or in those with slowly progressive disease when significant symptoms develop. Combined liver-kidney transplantation is suggested for children with end-stage renal disease.

Post-Infectious Acute Cerebellar Ataxia in Children

Acute cerebellar ataxia is a relatively common neurologic disorder among children. Our aim was to characterize the clinical picture, etiology, and prognosis of acute cerebellar ataxia. The medical records of all children with a diagnosis of acute cerebellar ataxia hospitalized in our center and Hasharon Medical Center from 1990 to 2001 were reviewed. The diagnosis of acute cerebellar ataxia was based on the following criteria: acute onset of ataxia with or without nystagmus; absence of known genetic predisposing factors, such as familial degenerative disorders; and absence of drug intoxication, bacterial meningitis, and metabolic disorders. Thirty-nine children were identified; 54% were male; mean age at presentation was 4.8±3.8 years. All patients were observed for at least 1 year. A prodromal febrile illness was noted in 74.4%: varicella, 31%; mumps, 20%; nonspecific viral infection, 15.4%; mycoplasma, 5%; Epstein Barr virus, 3%. Latency from the prodromal illness to the onset of ataxia was 8.8±7.4 days. The most common associated neurologic findings were nystagmus and dysmetria. Full gait recovery took less than 2 weeks on average, and the longest duration of neurologic signs was 24 days (mumps-related). Acute cerebellar ataxia in childhood is a self-limited disease. The recovery was faster than that reported in previous publications and was complete in all children without any neurologic sequelae. Imaging studies are needed only in atypical presentation or if there is no spontaneous improvement after 1 to 2 weeks.

New-onset post-transplantation food allergy in children--is it attributable only to the immunosuppressive protocol?

Abstract:  New‐onset post‐transplantation food allergy has been described mainly after liver transplantation, and its pathogenesis was attributed to the immunomodulatory effects of tacrolimus therapy. The aim of the present study was to evaluate the association of food allergy with solid organ transplantation in our center. The medical records of children who underwent kidney transplantation and children who underwent liver or liver and kidney transplantation from 1986 to 2005 were reviewed. A total of 189 children (124 after kidney transplantation, 65 after liver or liver and kidney transplantation) received tacrolimus as part of the immunosuppressive regimen. New‐onset post‐transplantation food allergy was documented in four of them: two with liver transplants and two with combined kidney and liver transplants. The absence of new‐onset food allergy in the children with isolated kidney transplants is compatible with other reports in the literature. This study supports the concept that the functioning liver itself, and not only tacrolimus immunosuppression, is a main contributor to food allergy in this patient population.

Methotrexate treatment in pediatric Crohn disease patients intolerant or resistant to purine analogues.

Background: Immunomodulatory drugs play a major role in maintaining remission and steroid sparing in children with Crohn disease. Although thiopurine agents are commonly used, unresponsiveness or intolerance to these drugs is common. The efficacy of methotrexate in maintenance of remission has been shown in adult Crohn disease; however, pediatric data are limited. Our goal was to evaluate the efficacy and safety of methotrexate in induction and maintenance of clinical remission in children with active Crohn disease who failed thiopurine treatment. Patients and Methods: In a retrospective multicenter study, efficacy of methotrexate in inducing and maintaining remission or response was assessed by Harvey-Bradshaw activity index, paediatric Crohn disease activity index and steroid use, in 25 children with Crohn disease, refractory or intolerant to thiopurine analogues. Results: Crohn disease was diagnosed at a mean age of 11.1 ± 3.1 years and methotrexate was initiated at age 14.5 ± 3.1 years. The median methotrexate dose was 12.5 mg/m2. Remission was achieved in 16 patients (64%), and response in 6 patients (24%). Out of 18 patients treated for longer than 6 months, 83% were in remission or response after 12 months of treatment. The mean duration of remission and response was 10.8 ± 8.8 months. Steroid withdrawal was possible in 12/16 patients (75%) receiving steroids at methotrexate introduction. Adverse effects were observed in 6 patients (24%) including nausea and vomiting in 3, elevation of liver enzymes in 2 and pancreatitis in 1 patient. Conclusions: Methotrexate is beneficial in maintaining remission and steroid-sparing treatment in children with Crohn disease following failure of thiopurine therapy.

The Role of Duodenal Bulb Biopsy in the Diagnosis of Celiac Disease in Children

Background and Study Aims It is suggested that for celiac disease (CD) diagnosis, biopsies should also be taken from the duodenal bulb. Whether bulb biopsies suggestive of CD can be found on upper gastrointestinal endoscopy (EGD) done for reasons other than CD diagnosis is not clear. The aim of our study was to evaluate the contribution of routine bulb biopsies to the diagnosis of CD, when taken regardless of prior suspicion of CD. Methods The study included 96 children who underwent EGD for suspected CD and a control group of 69 children who underwent EGD for reasons other than CD. The mucosal changes were evaluated using the Marsh-Oberhuber classification. Results Among the 87 children diagnosed with CD, we identified 6 patients (7%) with typical histologic findings only in the bulb (Marsh 3), but also 1 patient (1.1%) with findings only in the distal duodenum (Marsh 2). In 20 patients (23%) the histological changes were more severe in the bulb. One patient had more prominent findings in the second part of the duodenum. None of the control patients had histological changes compatible with CD in the bulb or the second part of the duodenum. Conclusions Our findings suggest that when CD is suspected, biopsies should be taken from both locations (bulb and second part) as mucosal changes may emerge only at one site. Nevertheless, the presence of characteristic histology on duodenal bulb biopsies might be sufficient for the diagnosis of CD.

The efficacy and safety of valganciclovir vs. oral ganciclovir in the prevention of symptomatic CMV infection in children after solid organ transplantation

Lapidus‐Krol E, Shapiro R, Amir J, Davidovits M, Steinberg R, Mor E, Avitzur Y. The efficacy and safety of valganciclovir vs. oral ganciclovir in the prevention of symptomatic CMV infection in children after solid organ transplantation.
Pediatr Transplantation 2010: 14:753–760.

Faecal occult blood in children with coeliac disease.

Abstract It has recently been suggested that in adults with coeliac disease, faecal blood loss may play a role in the development of iron deficiency. A group of 45 children diagnosed with coeliac disease during 1996 and 1997 were therefore prospectively evaluated for the presence of gluten in their diet, iron deficiency anaemia, and faecal occult blood. Sixty children admitted for elective surgery or asthma served as controls. Faecal occult blood was found in four iron deficient children on normal diet, of whom three were newly diagnosed. Occult blood loss disappeared in three of the four children when gluten was removed from their diet. Faecal occult blood was found in 26.7% of children on gluten-containing diet, but not in children on gluten-free diet (P=0.01), or in control children (P=0.001). Conclusion Our data suggest that the incidence of occult blood loss in coeliac disease occurs mainly in newly diagnosed cases and responds to a gluten-free diet. Occult blood testing may not be warranted in the absence of iron deficiency anaemia nor in children with iron deficiency anaemia who are on a gluten-free diet.

Erythropoietin increases survival and attenuates fulminant hepatic failure injury induced by D-galactosamine/lipopolysaccharide in mice.

Background. Liver transplantation is the only therapy of proven benefit in fulminant hepatic failure (FHF). Lipopolysaccharide (LPS), d-galactosamine (GalN)-induced FHF is a well-established model of liver injury in mice. Erythropoietin has a powerful tissue-protective effect in animal models. The aim of this study was to investigate the effect and mechanism of recombinant human erythropoietin (rhEPO) administration in FHF mice. Methods. C57BL/6 (n=42) mice were studied in vivo in a fulminant model induced by GalN/LPS. rhEPO was administered 30 min after the induction of FHF. Serum liver enzymes and hepatic tumor necrosis factor (TNF)-&agr; and interleukin (IL)-1&bgr; levels were determined. Histologic analysis was performed, and apoptotic cells were identified by immunohistochemistry for caspase-3. Nuclear factor (NF)-&kgr;B and c-Jun-N-terminal kinase (JNK) activation were studied using Western blot analysis. Results. After the induction of FHF, all control mice died within 12 hr of GalN/LPS administration. However, 83% of mice that were administered rhEPO were alive 2 weeks later, and overall survival improved (Kaplan-Meier, P<0.001). The serum liver enzymes, hepatic TNF-&agr; and IL-1&bgr; levels, liver histologic injury, and apoptotic hepatocytes were significantly reduced in FHF mice that were administered rhEPO compared with untreated mice. A significant decrease in hepatic NF-&kgr;B and JNK activation was noted in FHF rhEPO-treated mice compared with FHF untreated mice. Conclusions. The administration of rhEPO brought about increased survival and attenuation of the hepatic injury. This was associated with decreased hepatic NF-&kgr;B and JNK activation and thus TNF-&agr; and IL-1&bgr; levels. These findings have important implications for the potential use of rhEPO in FHF.

Childhood protein-losing enteropathy associated with Helicobacter pylori infection.

Helicobacter pylori was found in a gastric biopsy specimen of a child with protein-losing gastropathy. Through erythromycin therapy, clinical and ultrasonographic recovery was associated with the disappearance of the pathogen on repeated biopsy. The association of H. pylori with protein-losing gastropathy has been reported only once in children, to our knowledge. Although the causative correlation between the pathogen and the disease has not been proven yet, we suggest that future cases of protein-losing gastropathy be studied for the presence of H. pylori and followed up by ultrasonographic investigation and urea breath test. Appropriate treatment should be given to suspected cases.

Antibody response to influenza vaccine in pediatric liver transplant recipients.

Background: Data on the immunogenicity of the influenza vaccine in children after liver transplantation are sparse. Our study aims to evaluate the response of such patients to the trivalent influenza vaccine, administered by different protocols in 2 influenza seasons. Methods: Children attending the Liver Transplantation Unit of a tertiary care medical center were prospectively recruited and immunized with the inactivated subvirion influenza vaccine during the influenza seasons of 2004/2005 (1 dose, n = 18) and 2005/2006 (2 doses 4–6 weeks apart, n = 32). Antibodies were measured by hemagglutination inhibition assay. Immunity was defined as a titer of ≥1:40, and response was defined as a ≥4-fold increase in antibody titer from baseline. Results: In 2004/2005, the proportions of patients with protective antibodies were similar before and after 1 dose of vaccine. We found significant difference after the first dose for the A/H3N2 Wisconsin strain (43.2% vs. 70.3%, P = 0.003) and B/Malaysia strains (8.1% vs. 35.1%, P = 0.003) and for A/H1N1 New Caledonia strain (48.6% vs. 64.9% vs. 75%, P = 0.08, 0.005, respectively) after the second dose in 2005/2006 season. In 2004/2005, geometric mean titers rose significantly (P = 0.03) for the A/H3N2 New York strain; in 2005/2006, geometric mean titers for A/H3N2 New York and B/Malaysia increased after the first dose and for A/H1N1 New Caledonia after the second dose. Antibody titers were unrelated to age at transplantation, time from transplantation, and number of immunosuppressive drugs used. No serious vaccine-related events were documented. Conclusions: Liver-transplanted children respond to influenza vaccination. For some strains, the response is similar to that reported for healthy children. A second vaccine dose yielded no statistically significant benefit.