Search

Background: Niemann-Pick disease type C (NPC) is a fatal, autosomal recessive lysosomal storage disease which may present in infancy with cholestatic jaundice and/or hepatosplenomegaly. In cholestatic patients with splenomegaly, a bone marrow aspirate has been advocated as a relatively accessible tissue to demonstrate storage phenomena. Typically in patients with NPC, macrophages with abnormal cholesterol storage, so called foam cells, can be detected in the bone marrow., Aim: To review our experience of bone marrow aspiration in children with NPC presenting with infantile liver disease., Methods: A retrospective analysis of 11 consecutive children (8 males) from Birmingham Children's Hospital with NPC presenting with infantile liver disease was undertaken. The diagnosis of NPC was confirmed in all cases by demonstrating undetectable or low rates of cholesterol esterification and positive filipin staining for free cholesterol in cultured fibroblasts., Results: The median age at presentation was 1.5 months (range 0.5-10). Bone marrow aspirates showed storage cells in only 7/11 cases. Bone marrow aspirates which had storage cells were undertaken at a median age of 11 months while those with no storage cells were undertaken at median age 2.3 months. The overall sensitivity of bone marrow aspirates for detecting storage cells in children presenting with infantile liver disease was 64%; however, for children who had bone marrow aspirates in the first year of life it was only 57%., Conclusions: The sensitivity of bone marrow aspirate for the diagnosis of NPC disease in patients presenting with infantile liver disease was lower than previously reported. Where NPC is suspected clinically, definitive investigations should be undertaken promptly. There is a need to develop sensitive screening methods for NPC in children presenting with infantile liver disease.

Most metabolic liver diseases that affect pediatric patients present in the neonatal period with either cholestasis or acute liver failure. Metabolic liver disease in the older child has considerable overlap with adult patients. New diagnostic methods and therapy, including liver transplantation, has radically changed the outcome of many metabolic liver diseases.

Objective: To study the metabolism of single doses of paracetamol in paediatric patients with chronic liver disease admitted to a hospital liver disease clinic., Results: Thirteen paediatric patients, aged 7 months to 12 years, with chronic liver disease of varying severity were studied. In these children, paracetamol elimination half-life was negatively correlated with serum albumin and positively with prothrombin time, as previously reported in adults with liver disease. The rate constant of glucuronide formation was higher in the children with liver disease compared to the value reported in healthy children of similar ages. The rate constant of the formation of paracetamol sulphate was no different from that in normal children. The 36 h urinary paracetamol glucuronide to sulphate ratio was 1.4 (95% CI 0.8 to 1.7). This mean ratio was higher than in healthy children (0.81 and 0.75) but not significantly so, probably because of a Type 1 error due to the inevitable small sample size arising from the nature of the population being studied., Conclusion: The present study provides reassuring additional data to indicate that, at least for single doses, there is no cause for concern in the use of paracetamol in children with chronic liver disease.

A high-performance liquid chromatographic (HPLC) assay of paracetamol and its metabolites is described. The method for quantifying the metabolism of paracetamol in children with chronic liver disease and the good correlation between plasma and salivary concentrations of paracetamol is demonstrated. Despite an increasing bias between the two methods with increasing concentration of paracetamol, it is concluded that salivary assay is satisfactory for characterising paracetamol pharmacokinetics in the group of patients studied.

The article offers information on liver transplantation in non-alcoholic steatohepatitis (NASH) patients. It mentions that NASH patients often have coexistent clinical issues that can change the outcome of liver transplantation. It mentions that the guidelines represent consensus opinion from the experts of liver transplantation in Great Britain.

Aim: To identify the clinical and biochemical risk factors associated with outcome of paracetamol induced significant hepatotoxicity in children. Methods: Retrospective case notes review of those with paracetamol overdose admitted from 1992 to 2002. Patients were analysed in two groups: group I recovered after conservative treatment and group II developed progressive liver dysfunction and were listed for liver transplantation. Results: Of 51 patients (6 moles, 45 females, aged 0.8-16.1 years), 6 (aged <7 years) received cumulative multiple doses, and 45 a single large overdose (median 345 mg/kg, range 91-645). The median (range) interval to hospital at presentation post-ingestion was 24 hours (4-65) and 44 hours (24-96) respectively in groups I and II. Patients received standard supportive treatment including N- acetylcysteine. All children in group I survived. In group II, 6/11 underwent orthotopic liver transplantation (OLT) and 2/6 survived; 5/11 died awaiting OLT. Cerebral oedema was the main cause of death. Children who presented Late to hospital for treatment and those with progressive hepatotoxicity with prothrombin time >100 seconds, hypoglycaemia, serum creatinine >200 µmol/l, ocidosis (pH <7.3), and who developed encephalopathy grade III, had a poor prognosis or died. Although hepatic transaminase levels were markedly raised in both groups, there was no correlation with necessity for liver transplantation or death. Conclusion: Accidental or incidental paracetamol overdose in children may be associated with toxic liver damage leading to fulminant liver failure. Delayed presentation and/or delay in treatment, and hepatic encephalopathy ⩾grade III were significant risk factors, implying poor prognosis and need for OLT. Prompt identification of high risk patients, referral to a specialised unit for management, and consideration for liver transplantation is essential. [ABSTRACT FROM AUTHOR]