Rivka Shapiro

Schneider Children's Medical Center of Israel, Petah Tikva, Central District, Israel

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Publications (31)63.25 Total impact

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    ABSTRACT: Data, on the kinetic and serum levels of immunoglobulins in the immediate post-liver transplantation (LTx) period, are sparse with existing studies limited to adults or case reports of children. The aim of this study is to describe the phenomenon of hypogammaglobulinemia (HGG) in the immediate post-transplantation period among children undergoing LTx. A retrospective 10-yr chart review was conducted of all children who underwent LTx at a fourth-level pediatric medical center. Fifty-seven, of the 76 children who underwent LTx, were included in the study. Seventeen (29.8%) (mean age, 6.8 ± 5.2 yr) had HGG (11-IgG, 1-IgG+IgA, 1-IgG+IgM, 4-IgG+IgA+IgM), detected at 2 to 25 d after transplantation. Abdominal fluid was drained for 5 to 42 d; the amount drained until detection of HGG measured 27-668 mL/kg. HGG was associated with increased infection rate 0.9 episodes/patient vs. 0.17 episodes/patient (p < 0.01) in children without detected HGG. In conclusion, HGG is not rare in the immediate post-LTx period in children, and it may place patients at increased risk of infection. Further studies are needed to delineate the rate of occurrence, risk factors, and clinical implications of hypogammaglobulinemia in this patient population.
    Clinical Transplantation 04/2013; · 1.63 Impact Factor
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    ABSTRACT: Zygomycetes infection is associated with a high mortality in transplant populations. We describe a child with liver allograft Rhizopus oryzae infection who was salvaged by liver re-transplantation. A 10-year-old child presented with anastomotic bile leak that was repaired. A combined antibiotics and voriconazole regimen was introduced for Escherichia coli and Candida krusei growth in the peritoneal fluid. Despite broad antibiotic and antifungal coverage, the patient continued to have an ongoing infection. A follow-up computed tomography scan 8 weeks later showed 2 liver abscesses infiltrating the stomach and the diaphragm, with splenic infarcts and pericardial effusion. Aspirated samples from the liver abscess and the pericardial fluid revealed R. oryzae. Immunosuppression was discontinued and an antifungal regimen combining amphotericin B, posaconazole, and caspofungin was introduced. After 3 weeks of treatment with control of the systemic signs of infection, a positron emission tomography showed the fluorescence stain limited to the liver. With infection confined to the liver, the child underwent liver re-transplantation, splenectomy, and partial gastrectomy. Immunosuppression was reintroduced with recovery of the immune response observed by the CD4 cells adenosine triphophate release (Cylex(™) ImmuKnow(®) assay) and posaconazole was continued for another year. At 3-year follow-up, the child maintained normal graft function. We conclude that discontinuation of immunosuppression combined with a modern antifungal regimen may allow salvage re-transplantation in patients with liver mucormycosis.
    Transplant Infectious Disease 08/2012; 14(5):E97-E101. · 1.98 Impact Factor
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    ABSTRACT: Chronic renal failure (CRF) is a well-documented complication of liver transplantation. BK virus (BKV) is a common cause of CRF in renal-transplant recipients and has been sporadically associated with renal failure after nonrenal solid-organ transplantation. The aims of the study were to determine the prevalence of BK viruria and viremia in pediatric liver-transplant recipients, assess the natural course of BKV infection over time, and examine the association between BKV positivity and renal function. A prospective, cross-sectional study of 59 pediatric liver-transplant recipients. Blood and urine samples were collected at enrollment for creatinine level and BKV polymerase chain reaction test. BKV-positive patients underwent repeated testing and follow-up. The medical files were reviewed for clinical data. Median age at enrollment was 11.5 years, and median time from transplantation was 61 months. One child (1.7%) had viremia, and nine children (15.3%) had viruria (median: 610 copies/mL). All cases of viruria/viremia resolved spontaneously, nine of them within 10 months. There were no significant differences in demographic or clinical variables between the BKV-positive and BKV-negative children. None of the BKV-positive patients had evidence of renal dysfunction. Pediatric liver-transplant recipients have a low prevalence of BK viruria/viremia. BKV infection is associated with low viral loads and resolves spontaneously within a relatively short period, without residua. BKV is not associated with CRF postliver transplantation. BKV testing should not be part of the routine follow-up of children after liver transplantation.
    Transplantation 08/2011; 92(8):943-6. · 3.78 Impact Factor
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    ABSTRACT: 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. 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)-α and interleukin (IL)-1β levels were determined. Histologic analysis was performed, and apoptotic cells were identified by immunohistochemistry for caspase-3. Nuclear factor (NF)-κB and c-Jun-N-terminal kinase (JNK) activation were studied using Western blot analysis. 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-α and IL-1β 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-κB and JNK activation was noted in FHF rhEPO-treated mice compared with FHF untreated mice. The administration of rhEPO brought about increased survival and attenuation of the hepatic injury. This was associated with decreased hepatic NF-κB and JNK activation and thus TNF-α and IL-1β levels. These findings have important implications for the potential use of rhEPO in FHF.
    Transplantation 07/2011; 92(1):18-24. · 3.78 Impact Factor
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    ABSTRACT: Tumor necrosis factor α (TNF α) inhibitors (Infliximab) have proven useful in inflammatory bowel disease. There is experimental evidence implicating TNF α in acute rejection in organ transplantation suggesting that TNF blockade may be beneficial. This is the first report of the successful use of Infliximab in 2 pediatric patients with refractory intestinal acute rejection. The dramatic clinical and histological improvement in these children suggests a possible role for TNF α antagonists in acute small bowel rejection.
    Journal of pediatric gastroenterology and nutrition 06/2011; 54(4):565-7. · 2.18 Impact Factor
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    ABSTRACT: The aim of this study was to assess the prevalence and risk factors of AI in pediatric recipients of kidney or liver transplantation admitted because of a physiological stress episode and to identify patients that might be at risk of adrenal crises by clinical and laboratory parameters at admission. Adrenal function was prospectively evaluated by a standard (250 μg) adrenocorticotropin test in 48 recipients. Data on clinical and laboratory parameters were collected. AI was diagnosed in 11 patients: 10/32 (31.3%) children on long-term steroid treatment and 1/16 (6.25%) untreated. The only risk factor for AI was corticosteroids cumulative dose of >0.15 mg/kg/day during the last six months (p = 0.02, OR 6.67; 95% CI: 0.97-45.79). No correlation was found between clinical or laboratory signs of adrenal crisis on admission and the presence of AI. None of the patients with AI who did not receive stress dose (n = 8) developed adrenal crisis. AI is relatively common in children receiving prolonged corticosteroid treatment after kidney or liver transplantation. Clinical parameters on admission could not reliably identify patients with AI. Universal administration of a stress dose during physiological stress might not be required. However, at this point, the only method to identify patients that will benefit from a stress dose is through the ACTH test.
    Pediatric Transplantation 03/2011; 15(3):314-20. · 1.50 Impact Factor
  • The Israel Medical Association journal: IMAJ 02/2011; 13(2):111-2. · 0.98 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    Journal of clinical gastroenterology 01/2011; 45(1):26-9. · 2.21 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    The Pediatric Infectious Disease Journal 01/2011; 30(6):491-4. · 3.57 Impact Factor
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    ABSTRACT: To study the management and outcome of children with extrahepatic portal vein obstruction (EHPVO) in a whole country population. A nationwide multicenter retrospective case series of children with EHPVO was conducted. Data on demographics, radiographic studies, laboratory workup, endoscopic and surgical procedures, growth and development, were extracted from the patients' charts. Characteristics of clinical presentation, etiology of EHPVO, management and outcome were analyzed. Thirty patients, 13 males and 17 females, 19 (63.3%) Israeli and 11 (36.7%) Palestinians, were included in the analysis. Age at presentation was 4.8 ± 4.6 years, and mean follow-up was 4.9 ± 4.3 years. Associated anomalies were found in 4 patients. The incidence of EHPVO in Israeli children aged 0-14 years was 0.72/million. Risk factors for EHPVO were detected in 13 (43.3%) patients, including 9 patients (30%) with perinatal risk factors, and 4 patients (13.3%) with prothrombotic states: two had low levels of protein S and C, one had lupus anticoagulant, and one was homozygous for methyltetrahydrofolate reductase mutations. In 56.6% of patients, no predisposing factors were found. The most common presenting symptoms were an incidental finding of splenomegaly (43.3%), and upper gastrointestinal bleeding (40%). No differences were found between Israeli and Palestinian children with regard to age at presentation, etiology and clinical symptoms. Bleeding occurred in 18 patients (60%), at a median age of 3 years. Sclerotherapy or esophageal banding was performed in 20 patients. No sclerotherapy complications were reported. Portosystemic shunts were performed in 11 patients (36.6%), at a median age of 11 (range 3-17) years: splenorenal in 9, mesocaval in 1, and a meso-Rex shunt in 1 patient. One patient underwent splenectomy due to severe pancytopenia. Patients were followed up for a median of 3 (range 0.5-15) years. One patient died aged 3 years due to mucopolysaccharidase deficiency type III. None of the patients died due to gastrointestinal bleeding. EHPVO is a rare disorder. The etiological factors are still mostly unknown, and the endoscopic and surgical treatment options ensure a good long-term prognosis.
    World Journal of Gastroenterology 10/2010; 16(39):4968-72. · 2.55 Impact Factor
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    ABSTRACT: Routine prophylaxis for CMV with valganciclovir is common in adult recipients but data to support its use in children are scarce. The aim of this study was to compare the efficacy and safety of valganciclovir vs. ganciclovir in a pediatric cohort. We performed a retrospective analysis of 92 children after KTx and/or LTx. All children have received IV ganciclovir for two wk, and then oral ganciclovir (TID; n = 41) before 2004, or valganciclovir (OD; n = 51) thereafter. Treatment was given for three months in R+/D+ or R+/D- recipients and for six months in R-/D+. Patients were followed for one yr post transplant. Both groups were comparable in their demographic and transplant-related history. Symptomatic CMV infection/disease developed in 13.7% vs. 19.5% of valganciclovir and ganciclovir groups, respectively (P-NS). Time-to-onset of CMV infection was comparable in both groups (P-NS); rates of acute allograft rejection were similar in both groups (3.9% vs. 9.8%). Risk factors for CMV infection included young age, serostatus of R-/D+, and allograft from cadaver donor. No significant side effects were noted in both groups. As in adults, valganciclovir appears to be as efficacious and safe as oral ganciclovir. Valganciclovir should be considered as a possible prophylactic treatment for CMV in pediatric recipients of KTx or LTx.
    Pediatric Transplantation 09/2010; 14(6):753-60. · 1.50 Impact Factor
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    ABSTRACT: Progressive familial intrahepatic cholestasis (PFIC) is a group of rare heterogeneous autosomal recessive disorders characterized by metabolic defects in biliary proteins involved in the formation and transfer of bile acids in the liver. The genotype-phenotype correlation is not always clear. Mutations in the ATP8B1, BSEP and MDR3 genes have been associated with PFIC1, PFIC2 and PFIC3, respectively. This study sought to characterize the molecular genetic basis for PFIC subtypes in Israel. It was conducted on 14 children with PFIC and their families; 10 with a PFIC1 or PFIC2 phenotype and 4 with a PFIC3 phenotype. Using denaturing high-performance liquid chromatography (DHPLC), five different mutations were identified in four affected families: three novel mutations in BSEP (G19R-g181c, S226L-c803t and G877R-g2755a), one novel mutation in MDR3 (IVS14+6 t/c) and one heterozygous mutation in ATP8B1 (R600W, in a family with the PFIC1/PFIC2 phenotype). The cause of PFIC was identified in 20% of the families tested. These findings indicate the probable involvement of additional genes in PFIC and the need for further studies to determine whether the abnormality lies on the RNA or protein level. A better understanding of the phenotype-genotype correlation in PFIC will lead to improved diagnoses and treatments.
    Journal of Human Genetics 04/2010; 55(5):308-13. · 2.53 Impact Factor
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    ABSTRACT: 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. 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. 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. Methotrexate is beneficial in maintaining remission and steroid-sparing treatment in children with Crohn disease following failure of thiopurine therapy.
    Journal of pediatric gastroenterology and nutrition 06/2009; 48(5):526-30. · 2.18 Impact Factor
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    ABSTRACT: Liver transplantation is considered the treatment of choice for most children with deteriorating fulminant hepatic failure (FHF). Living-related donor liver transplantation (LDLT) has been suggested as an alternative to cadaveric liver transplantation to overcome the shortage of organ donors. However, experience with LDLT for children with FHF is limited in the Western world. To present the experience with LDLT for children with FHF in a major referral center in Israel. The files of all children who underwent primary LDLT for FHF were reviewed for demographic, clinical, and laboratory parameters before and after transplantation. : During 1996 to 2007, 13 children diagnosed with FHF underwent primary LDLT. Median age was 4 years (range 0.75-14 years); the causes of FHF were acute hepatitis A in 4 patients and were unknown in 9 patients. Short-term complications, documented in 12 children, included mainly hepatic artery thrombosis (n = 5), which warranted retransplantation in 3 cases, and biliary leaks (n = 3). Three patients died within the first month after LDLT of severe intraoperative bleeding (n = 1), severe brain edema (n = 1), and multiorgan failure (n = 1). Long-term complications were less common and included mainly ascending cholangitis (n = 3). Patient survival rate was 68% at 1 year and 57% at 5 years. None of the donors had long-term complications. Among children with FHF, LDLT can serve as a timely and lifesaving alternative to cadaveric donation, and could reduce the dependence on cadaveric livers in this setting.
    Journal of pediatric gastroenterology and nutrition 05/2009; 48(4):451-5. · 2.18 Impact Factor
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    ABSTRACT: Information on safety and efficacy of adalimumab in children with Crohn's disease (CD) is limited. We present a case-series of 14 children with severe CD treated with adalimumab during a 3.5-year period. Fourteen children (nine boys, five girls), aged 13.9 years (range 1.9-19.1) were treated with adalimumab during 12.5 months (range 7-42). All had steroid or immunosuppression-drugs refractory disease. Ten patients (71%) had been previously treated with infliximab, 13/14 were treated with different immunosuppressive drugs and all were steroid-dependent or resistant. Seven children (50%) showed full clinical response and 5/14 (35%) improved partially. Two children (15%) had loss of response after a period of transient improvement. Adalimumab treatment enabled complete steroids withdrawal in 8/14 (57%) of steroid-dependent children. Currently, five children are in complete remission with adalimumab monotherapy for a median 14 months (range 9-24). Adalimumab may induce and maintain remission in children with severe, refractory CD. Prospective safety and efficacy confirmation of this data in children is necessary.
    Digestive Diseases and Sciences 04/2009; 55(3):747-53. · 2.26 Impact Factor
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    ABSTRACT: Lifelong immunosuppression is mandatory for optimal graft and patient survival following liver transplantation. Nevertheless, graft rejection or numerous adverse events associated with overimmunosuppression or underimmunosuppression cannot be completely avoided. The ImmuKnow assay measures cell-mediated immunity and is able to discern between conditions of overimmunosuppression and underimmunosuppression. The aim of this study was to evaluate the ImmuKnow assay in the evaluation of the immune function in pediatric liver transplant recipients and to assess its correlation with the patients' clinical and biochemical status. Eighty-nine whole blood samples were collected from 23 liver transplant recipients that were 1 to 18 years old. The net state of immune function was determined by the quantitative measurement of the intracellular adenosine 5-triphosphate level in CD4+ lymphocytes after phytohemagglutinin stimulation. Comprehensive clinical data were correlated with the ImmuKnow assay results. In 23 of the 28 samples collected during clinical quiescence, ImmuKnow results were correlated with the clinical status, expressing the patient's moderate immune function. However, a correlation between measured therapeutic drug levels and clinical quiescence was found in only 18 of the 28 samples. In 6 patients who suffered from clinical complications, ImmuKnow measurements showed a wide range of deviations, expressing the unstable immunological status of these patients. In conclusion, the ImmuKnow assay correlates with the clinical status of liver-transplanted children. It serves as a reliable and unique parameter of the cellular immune function. We conclude that the ImmuKnow assay, together with existing clinical tools, may allow for the immune monitoring of pediatric liver recipients.
    Liver Transplantation 07/2008; 14(6):893-8. · 3.94 Impact Factor
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    ABSTRACT: Gingivostomatitis is a common clinical manifestation of primary herpes simplex virus type 1 (HSV-1) infection in children. The most common complication of herpetic gingivostomatitis is dehydration; rarely, it may be complicated by secondary bacteremia, and Kingella kingae and group A Streptococcus infections have been reported to be responsible for such episodes. We describe the clinical course of a 4.5-year-old girl several years after a liver transplantation, who presented with high fever, vesicular lesions in the buccal region, and cervical lymphadenopathy. Viral culture from the vesicles grew HSV-1, whereas blood culture and bacterial culture from the vesicles grew methicillin-sensitive Staphylococcus aureus with identical antibiogram. Serology against HSV-1 confirmed a recent infection. The child was treated with cephalexin and improved gradually. Herpetic lesions of the oral mucosa might serve as a port of entry for pathogens including Staphylococcus aureus. Pediatricians and dentists should be aware of bacterial complications in children with herpetic stomatitis.
    Journal of Periodontology 03/2008; 79(2):376-8. · 2.40 Impact Factor
  • Transplantation 01/2008; 86. · 3.78 Impact Factor
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    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.
    Pediatric Transplantation 01/2008; 13(1):63-9. · 1.50 Impact Factor
  • Transplantation 01/2008; 86. · 3.78 Impact Factor

Publication Stats

198 Citations
63.25 Total Impact Points

Institutions

  • 2001–2012
    • Schneider Children's Medical Center of Israel
      Petah Tikva, Central District, Israel
  • 2010
    • Ministry of Health (Israel)
      Yerushalayim, Jerusalem District, Israel
  • 2008
    • Rabin Medical Center
      • Department of Cardiology
      Tell Afif, Tel Aviv, Israel
  • 2000
    • Tel Aviv University
      Tell Afif, Tel Aviv, Israel