Hepatitis C infection in children: a Melbourne perspective

OBJECTIVE: To examine the clinical spectrum of hepatitis C virus (HCV) infected children in our care by determining presentation, mode of acquisition, degree of co-infection, biochemical evidence of persisting hepatitis and treatment outcome. METHODOLOGY: A retrospective review of the medical records of all children attending the Royal Children's Hospital, Melbourne, between 1990 and 1998, who had antibodies to HCV infection detected. Detailed clinical information, investigations and the results of treatment were extracted from the clinical notes. RESULTS: A total of 94 children (age range 2 weeks to 19.7 years) were identified, of whom nine had passive transfer of maternal antibodies from HCV-positive mothers and were excluded from analysis. Sixty-seven children (79%) were infected by transfusion of blood or blood products. Perinatal transmission occurred in 11 children (13%), and six children (7%) had a history of i.v. drug abuse. The majority of children were asymptomatic at presentation. Of the 65 patients tested for HCV-ribonucleic acid, 43 (66%) were positive. Fifty-seven cases had serial alanine aminotransaminase (ALT) measurements over a mean of 28 months. Of these, 38 (67%) had an abnormal ALT. Ten cases (12%) were co-infected with hepatitis B virus, HIV or both. Of 12 patients treated with interferon, four responded with normalisation of ALT from 3 to 12 months post-commencement of therapy. CONCLUSIONS: Although HCV was largely an asymptomatic condition in our clinic population, more than half the patients had biochemical evidence of ongoing liver damage. Given the chronicity of this infection in the majority of patients and the long-term risks of cirrhosis and hepatocellular carcinoma, children with HCV infection represent a high-risk group worthy of regular follow up.     

Risk of hepatitis C virus infection in multiply transfused premature neonates

BACKGROUND: Reports from around the world indicate that multiply transfused patients are at increased risk of hepatitis C virus (HCV) infection, with reported rates of between 4% and 44%. Such reports are mostly of haematological and renal patients. As recipients of blood products in the newborn period, premature infants share this risk, but there is little information regarding their risk. AIM: To assess the risk of HCV infection in children who, as premature neonates, received multiple blood products prior to the introduction of screening of donated blood for HCV. METHODS: Premature infants born between January 1985 and January 1990 who had attended our high-risk follow-up clinic were selected on the basis of the number of transfusions of blood, platelets or fresh frozen plasma they received in the newborn period. Ethical approval to offer HCV testing to parents was obtained from the Central Sydney Area Health Service Ethics Review Committee. Parents of infants who received three or more transfusions were then contacted by mail with the approved letter explaining the study, and offered HCV testing. Detection of anti-HCV antibodies was undertaken using second, and later third generation enzyme immunoassay kits. Samples which were found to be 'indeterminate' were tested using a Wellcozyme HCV western blot assay (Murex Diagnostics Ltd, Datford, UK). Hepatitis C virus-ribonucleic acid (RNA) was detected using an 'in-house' polymerase chain reaction (PCR) assay. Alanine transaminase (ALT) was also measured, with values above 55 U/L considered abnormal. RESULTS: Consent was obtained for 45 children (25 males, 20 females). The mean (+/- SEM) gestational age and weight of the children at birth was 26.7 +/- 0.2 weeks and 938 +/- 27 g, respectively. The children received 198 transfusions of blood products, an average of 4.4 U per child. All of the infants except for one were negative for anti-HCV antibodies. One infant was 'indeterminate' (low positive on third generation test but negative on second generation test), but proved negative subsequently on both western blot and PCR testing. HCV-RNA was not detected in any of the infants on PCR testing. All of the samples had normal ALT values, the mean being 16 U/L (range 8-52). CONCLUSION: None of the children consenting to this study had evidence of current HCV infection. Because of the sample size, we were not able to estimate the true risk of infection from this study, except that the upper limit for the risk is about 1/200 per transfused blood sample.     

Diagnosis and management of paediatric hepatitis C virus infection

Hepatitis C virus (HCV) infection in children is uncommon and there are few guidelines indicating optimal management. It is estimated that 125-250 children are infected vertically with HCV in Australia each year and very few of these children are diagnosed and followed medically. Without accurate diagnosis and follow up, these children cannot be offered optimal care, and are at risk of presenting in adult life with significant liver pathology and long-term sequelae.     

丙型肝炎病毒感染与自然杀伤细胞介导的抗病毒固有免疫

丙型肝炎病毒(hepatitis C virus,HCV)感染已成为全球重要的公共卫生问题。固有免疫在丙型肝炎的致病机制中发挥了重要作用。在不同的固有免疫细胞中,在肝脏中含量丰富的自然杀伤(natural killer,NK)细胞在HCV感染中的作用近年来更是研究的热点之一。文章对HCV感染与NK细胞介导的抗病毒固有免疫之间的相互作用进行了阐述。     

Hepatitis B precore mutant in children with chronic hepatitis B virus infection

BACKGROUND: In adults, hepatitis B virus (HBV) with a G to A point mutation at nucleotide 83 in the precore region (mutant HBV 83), is commonly found in HB e antibody positive HBV carriers. It has been reported that this mutant is not able to produce HB e antigen. The exact prevalence of mutant HBV 83 in patients with chronic HBV infection is not fully understood, especially in children. METHODS: To investigate the role of mutant HBV 83 in children with chronic HBV infection, sera were tested for the presence of mutant HBV 83 using a mutation site-specific assay. RESULTS: Mutant HBV 83 was detected in 15 of 22 children (68%). Seven children were followed longitudinally, of which three were asymptomatic carriers and the other four had chronic hepatitis B on entry. There was no clear relationship between the disease activity and the presence of mutant HBV 83. CONCLUSIONS: It was concluded that mutant HBV 83 is commonly present in children with chronic HBV infection and this mutant is not necessarily associated with activation of hepatitis.     

Hodgkin's disease in association with Down syndrome: a case report

The increased incidence of malignancies, especially acute leukemia, in Down syndrome has been clearly established. The association of Hodgkin's disease with Down syndrome has not been extensively documented, and only a few cases have been reported. We present here a case report of Hodgkin's disease in an 11-year-old female child with Down syndrome. The child presented with a stage IVB nodular sclerotic Hodgkin's disease and died of progressive disease. We also present a brief review of the mechanisms of development of malignancy in Down syndrome.     

Increasing incidence of congenital heart disease in patients with Down syndrome

ABSTRACT Our impression that the incidence of congenital heart disease in patients with Down syndrome was increasing in our outpatient clinic was investigated. The change in the incidence of congenital heart disease was investigated during the period from January 1981 to December 1998 in 196 patients with Down syndrome diagnosed by chromosomal analysis. Of the 196 patients, 99 (50.5%) had congenital heart disease. The incidence increased during study period: 35.4% (1981–1983), 44.9% (1984–1986), 46.4% (1987–1989), 69.0% (1990–1992), 53.8% (1993–1995), and 81.3% (1996–1998). The number and the mean age of new outpatients were found to decrease. The incidence of Down syndrome patients whose disease was chromosomally proven by other institutions was increasing. The incidence of congenital heart disease in patients with Down syndrome is currently increasing in our outpatient clinic. However many factors might contribute to this phenomenon.     

Echocardiography in children with Down syndrome

Congenital heart disease is a common problem in children with Down syndrome (DS). Echocardiography plays an important role in the detection of both structural and functional abnormalities in this group of patients. Fetal echocardiography can help in the early recognition of DS by detecting soft markers of DS, but its main role is to define the exact nature of the suspected cardiac problem in the fetus. Postnatal echocardiography is mandatory in the first month of life for all neonates with DS. It is also indicated before any cardiac surgery and for serial follow-up after cardiac surgery. In this article, we discuss the types and mechanism of cardiac abnormalities in DS children and the role of both fetal and postnatal echocardiography in the detection of these abnormalities.     

Interferon therapy for Japanese hemophiliacs with chronic hepatitis C

Eight Japanese hemophiliacs with chronic hepatitis C (CHC) received interferon (IFN) therapy and four of them (50%) responded completely. Non-responders included 3 double-infected patients: I with hepatitis B virus (HBV) and 2 with human immunodeficiency virus-1 (HIV-1). In one of the patients with HIV-1 double infection, the absolute number of CD4* lymphocytes decreased during IFN therapy. These findings suggest that hemophiliac patients with CHC can respond well to IFN therapy, but in patients who are double-infected with HBV and HIV-1, the indication of IFN therapy should be considered seriously.     

Treatment of HCV infection with interferon alpha-2b and ribavirin in a patient with X-linked lymphoproliferative syndrome

Chronic hepatitis C (HCV) infection in patients with primary immunodeficiency increases the risk of an accelerated progression of HCV-related liver disease. Here, we report a patient with X-linked lymphoproliferative syndrome infected with HCV and Epstein-Barr virus (EBV). After combination treatment with interferon α-2b and ribavirin, clearance of HCV-RNA was achieved, and noteworthily, EBV DNA also became undetectable.     

Comparison of different therapy approaches in children with Down syndrome

BACKGROUND: Children with Down syndrome have sensory integrative dysfunction as a result of limited sensory experience from lack of normal motor control. The aim of the present study was to compare the effects of sensory integrative therapy alone, vestibular stimulation in addition to sensory integrative therapy and neurodevelopmental therapy, on children with Down syndrome. METHODS: The present study was carried out at the Occupational Therapy Unit, School of Physical Therapy and Rehabilitation of Hacettepe University. Forty-five children who were diagnosed as having Down syndrome by the Departments of Paediatric Neurology and Medical Genetics at Hacettepe University were assessed and randomly divided into three groups. Sensory integrative therapy was given to the first group (n=15), vestibular stimulation in addition sensory integrative therapy was given to the second group (n=15) and neurodevelopmental therapy was given to the third group (n=15). All children were evaluated with Ayres Southern California Sensory Integration Test, Pivot Prone Test, Gravitational Insecurity Test and Pegboard Test. The hypotonicity of extensor muscles, joint stability, automatic movement reactions and locomotor skills were tested. Treatment programs were 1.5 h per session, 3 days per week for 3 months. RESULTS: When these groups were compared, statistically significant differences were found in subjects' performance of balance on right foot-eyes open, pivot prone position-quality score and locomotor skills-front tests (P<0.05). There were no significant differences in the other tests (P>0.05). CONCLUSIONS: The results of the present study showed that sensory integration, vestibular stimulation and neurodevelopmental therapy were effective in children with Down syndrome. It was concluded that when designing rehabilitation programs for children with Down syndrome, all treatment methods should be applied in combination, and should support each other according to the individual needs of the child.     

Elevated intracellular calcium in neutrophils in patients with Down syndrome

Background:  Neutrophils of patients with Down syndrome (DS) are known to have numerous abnormalities associated with diminished resistance to infection. The intracellular calcium (Ca²⁺i) acts as a second messenger and regulates diverse functions in many cell types. The purpose of the present study was to compare the intracellular calcium concentration ([Ca²⁺]i) at baseline and stimulated conditions in DS patients and in normal subjects to investigate [Ca²⁺]i regulation in neutrophils.
Methods:  The study group consisted of 27 subjects with DS (age, 8.6 ± 4.6 years) and 14 healthy subjects (age, 12.0 ± 3.9 years). Using a fluorescent probe, fura-2, the baseline levels and changes in [Ca²⁺]i were examined after stimulation of neutrophils with N -formyl-methionyl-leucyl-phenylalanine (fMLP).
Results:  At baseline, the [Ca²⁺]i of neutrophils from DS subjects was significantly higher than that of the controls (70.6  ±  28.0  nmol/L vs 44.4 ± 16.0 nmol/L, P < 0.01). The absolute [Ca²⁺]i after addition of fMLP in the DS subjects was also significantly higher than that of the control group (250 ± 91 nmol/L vs 167 ± 60 nmol/L, respectively: P  < 0.01). The neutrophils from the DS subjects had a consistently and significantly prolonged response to fMLP as compared to the neutrophils of control subjects.
Conclusions:  The higher [Ca²⁺]i and the prolonged response of [Ca²⁺]i to fMLP appear to be phenotypic traits of neutrophils in subjects with DS. This suggests intrinsic cellular defects in DS.     

Prevalence and diagnostic significance of gliadin antibodies in children with Down syndrome

Malabsorption appears common in patients with Down syndrome. We determined gliadin antibodies (IgG and IgA) in 78 children (aged 1–19 years) with Down syndrome and found increased IgG levels in 23, increased IgA levels in 2 and both increased IgG and IgA levels in 6 patients. Two patients with increased IgG and IgA had coeliac disease, two others had no mucosal abnormalities. There is an increased frequency of gliadin antibodies in patients with Down syndrome. In addition, an increased incidence of coeliac disease in this population cannot be excluded.     

Down syndrome and coeliac disease: five new cases with a review of the literature

We report five new patients with coeliac disease and Down syndrome and review the 11 cases previously reported in the literature. In 14 of these 16 patients diarrhoea was the presenting symptom and in 2 failure to thrive in combination with anaemia. The frequency of coeliac disease in children with Down syndrome was calculated as being 43 times greater than in children without Down syndrome. Delay between first symptoms and diagnosis in patients with combined coeliac disease and Down syndrome was 2.5 years, while in the other children with coeliac disease it was only 8 months. This distinctive difference could be caused by an underestimation of the seriousness of gastro-intestinal complaints in patients with Down syndrome. It is stressed that coeliac disease should be strongly considered in all children with Down syndrome and either persistent diarrhoea or failure to thrive.     

Hepatitis B and C virus infections in Turkish children with haemophilia

We examined 41 Turkish children with haemophilia for evidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections using the enzyme-linked immunosorbent assay (ELISA). Hepatitis B surface antigen was found to be positive in 11 patients (26. 8%) and HCV-specific antibody (anti-HCV) was detected in 10 (24. 4%) patients. There was a close relationship of the number of transfusions of blood plasma to the presence of HCV specific antibody, but not to the serum markers of HBV infection. In countries where HBV infection is commonly seen and problems in transfusion practice continue, as in Turkey, children with haemophilia are at greater risk for HBV and HCV infections.