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Background and purpose The severity of Wilson's disease ( WD) is linked to free copper accumulating in the liver and brain. Exchangeable copper (Cu EXC) is a new technique to determine plasmatic copper and is useful in the diagnosis of WD. It is hypothesized that it may also enable a good evaluation of extra-hepatic involvement and its severity. Methods Forty-eight newly diagnosed WD patients were prospectively evaluated using hepatic, neurological, ophthalmological and brain magnetic resonance imaging ( MRI) scores. Three phenotypic presentations were distinguished: pre-symptomatic, hepatic and extra-hepatic. Cu EXC was determined in addition to standard copper assays before decoppering therapy. Correlations between biological parameters and the different scores were determined and compared in the hepatic and extra-hepatic groups. Results Extra-hepatic patients had significantly higher Cu EXC values than those with the hepatic form ( P < 0.0001). The overall ability of Cu EXC to separate the two forms was satisfactory, with an area under the curve of 0.883 (95% confidence interval 0.771-0.996) and an optimal threshold for extra-hepatic diagnosis of 2.08 μmol/l (sensitivity 85.7%; specificity 94.1%). In extra-hepatic patients, Cu EXC was the only biological marker to be positively correlated with the Unified Wilson Disease Rating Score ( r = 0.45, P = 0.016), the Kayser−Fleischer ring score ( r = 0.46, P = 0.014) and the brain MRI score ( r = 0.38, P = 0.048), but it was not correlated with the hepatic score. Conclusions Exchangeable copper determination is useful when diagnosing WD as a value >2.08 μmol/l is indicative of the severity of the extra-hepatic involvement. In the case of purely hepatic presentation, atypical or mild neurological signs, it should encourage physicians to search for lesions in the brain and eyes. [ABSTRACT FROM AUTHOR]

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Context: A subset (approximately 3%-5%) of patients with cystic fibrosis (CF) develops severe liver disease with portal hypertension.Objective: To assess whether any of 9 polymorphisms in 5 candidate genes (alpha(1)-antitrypsin or alpha(1)-antiprotease [SERPINA1], angiotensin-converting enzyme [ACE], glutathione S-transferase [GSTP1], mannose-binding lectin 2 [MBL2], and transforming growth factor beta1 [TGFB1]) are associated with severe liver disease in patients with CF.Design, Setting, and Participants: Two-stage case-control study enrolling patients with CF and severe liver disease with portal hypertension (CFLD) from 63 CF centers in the United States as well as 32 in Canada and 18 outside of North America, with the University of North Carolina at Chapel Hill as the coordinating site. In the initial study, 124 patients with CFLD (enrolled January 1999-December 2004) and 843 control patients without CFLD were studied by genotyping 9 polymorphisms in 5 genes previously studied as modifiers of liver disease in CF. In the second stage, the SERPINA1 Z allele and TGFB1 codon 10 genotype were tested in an additional 136 patients with CFLD (enrolled January 2005-February 2007) and 1088 with no CFLD.Main Outcome Measures: Differences in distribution of genotypes in patients with CFLD vs patients without CFLD.Results: The initial study showed CFLD to be associated with the SERPINA1 Z allele (odds ratio [OR], 4.72; 95% confidence interval [CI], 2.31-9.61; P = 3.3 x 10(-6)) and with TGFB1 codon 10 CC genotype (OR, 1.53; 95% CI, 1.16-2.03; P = 2.8 x 10(-3)). In the replication study, CFLD was associated with the SERPINA1 Z allele (OR, 3.42; 95% CI, 1.54-7.59; P = 1.4 x 10(-3)) but not with TGFB1 codon 10. A combined analysis of the initial and replication studies by logistic regression showed CFLD to be associated with SERPINA1 Z allele (OR, 5.04; 95% CI, 2.88-8.83; P = 1.5 x 10(-8)).Conclusions: The SERPINA1 Z allele is a risk factor for liver disease in CF. Patients who carry the Z allele are at greater risk (OR, approximately 5) of developing severe liver disease with portal hypertension. [ABSTRACT FROM AUTHOR]

Abstract: A cross-sectional study was performed to assess quality of life (QoL) after kidney or liver transplantation during childhood. Self-questionnaires explored children, adolescent and parent QoL. Seventy-five transplant children, 36 transplant adolescents, 67 mothers, 34 fathers and 67 caregivers filled out the questionnaires; they were compared with a reference population. Children reported a rather good QoL, but their extra-family involvement appeared not as satisfactory as that of the reference population children. Adolescents reported a very high QoL when completing the structured format scale; however, their responses to open-ended questions showed qualitative differences compared with those of a reference population: they expressed concern about their body or health, less pleasure than ordinary adolescents to manage by themselves, and a poor relationship with peers. Mothers indicated a deep impact of the child's illness on their own QoL, and the need for psychological support. In conclusion, a rather good QoL is a long-lasting feature of kidney and liver transplantation in children. Such an assessment is mandatory to identify remaining impairments in some selected areas, either in the recipient or family. [ABSTRACT FROM AUTHOR]

Despite the availability of potent immunosuppressive drugs, rejection after organ transplantation in children remains a serious concern, and may lead to significant morbidity, graft loss, and death of the patient. Acute graft rejection in pediatric recipients is first treated with methylprednisolone pulses, followed by progressive taper of corticosteroid doses. After control of the rejection episode, baseline immunosuppression has to be adjusted and closely monitored since rejection (especially late episodes, occurring more than 6 months after transplantation) may be due to a lack of compliance or sub-therapeutic drug concentrations. The management of corticosteroid resistant rejection is not standardized, and depends on the transplanted organ and previous immunosuppressive regimen. In patients experiencing corticosteroid resistant acute rejection while on a cyclosporine-based immunosuppressive regimen, cyclosporine is generally changed to tacrolimus. In case of tacrolimus-based immunosuppression, tacrolimus blood levels may be increased, and/or mycophenolate mofetil (which nowadays tends to replace azathioprine) or sirolimus may be added, although pharmacodynamic data and clinical studies with these agents are still scarce in pediatric recipients. The use of antithymocyte globulins or monoclonal anti-CD3 antibodies, muromonab CD3 (OKT3) is hampered by numerous adverse effects, including a significant risk of over-immunosuppression. These therapies are nowadays indicated in very selected cases. Other treatments such as plasmapheresis and high dose immunoglobulins may be useful in difficult cases. In patients with refractory rejection despite therapeutic escalation, the risks of over-immunosuppression, including opportunistic infections and malignancies (especially the Epstein-Barr virus related post-transplant lymphoproliferative disease) have to be balanced with the consequences of graft loss due to rejection. Detransplantation or retransplantation may, in some instances, be preferable to severe infectious or tumoral complications. [ABSTRACT FROM AUTHOR]

Unlabelled: Most studies on the prevalence of asialoglycoprotein antibodies have involved adults. In this study the prevalence of antibodies to the human asialoglycoprotein receptor (ASGP-R) was determined in 63 children with auto-immune hepatitis. It was shown that 75% of those with auto-immune hepatitis type 1 and 40% of those with auto-immune hepatitis type 2 were positive and the presence of anti-ASGP-R auto-antibodies, at a mean titre of 1:1,600 and 1:1,000 respectively. No statistical significance was found between anti-ASGP-R positive and negative patients with respect to the median age at onset, proportion of females and ALT levels. However, the titre of anti-ASGP-R antibodies correlated significantly with hypergammaglobulinaemia.Conclusion: Anti-asialoglycoprotein receptor antibodies are frequently present in the sera of children with auto-immune hepatitis, particularly type 1, The presence of these antibodies is an indirect marker of inflammatory activity. [ABSTRACT FROM AUTHOR]

Acyclovir-induced neurotoxicity is a rare adverse effect, found especially in adults with pre-existing renal failure. We report a case of neurotoxicity of acyclovir in a six-month-old liver transplant recipient. Case report and review of literature are discussed. [ABSTRACT FROM AUTHOR]