Bocavirus infection following paediatric liver transplantation.

HBoV is an emergent virus, which is frequently detected as a co-infective agent. However, it can cause disease on its own. It is associated with respiratory and diarrhoeal illness in children and adults, whether immunocompetent or immunocompromised. We report HBoV infection in a child post-liver transplantation, who presented with persistent fever and mild tachypnea, 3 weeks after a successful transplant. She recovered spontaneously with no graft dysfunction.

Unusual shunt for symptomatic portal vein thrombosis after liver transplantation - Clatworthy revisited.

PV thrombosis is not an uncommon occurrence following pediatric LT. Symptomatic PHT following PV thrombosis is treated medically, surgical portosystemic shunting (mesorex, splenorenal, and mesocaval) being reserved for refractory cases. A 10-yr-old boy suffered recurrent malena and hemorrhagic shock because of chronic PV thrombosis following LT nine yr ago (1999). Extensive work-up failed to localize the bleeding source. The liver function remained normal. Initial attempts at surgical shunts failed owing to thrombosis (mesocaval 2001, splenorenal, inferior mesenteric-left renal vein, splenic-left external iliac vein 2008). In this situation, we performed a Clatworthy shunt by anastomosing the divided lower end of the LCIV to the side of SMV. There was a single, large caliber anastomosis. Post-operatively, the malena stopped completely, and clinically, there was no lower limb edema or encephalopathy. Doppler USG revealed persistence of hepatopetal flow within the portal collaterals. Follow-up at two yr reveals stable hepatic function with a patent shunt. To the best of our knowledge, we are not aware of a Clatworthy shunt being performed in a transplant setting. We reviewed the literature pertaining to this shunt in non-transplant patients with PHT.

Novel multiplex oligonucleotide-conjugated bead suspension array for rapid identification of enterovirus 71 subgenogroups.

A high-throughput multiplex bead suspension array was developed for the rapid subgenogrouping of EV71 strains, based on single nucleotide polymorphisms observed within the VP1 region with a high sensitivity as low as 1 PFU. Of 33 viral isolates and 55 clinical samples, all EV71 strains were successfully detected and correctly subgenogrouped.

Rates and determinants of antibiotics and probiotics prescription to children in Asia-Pacific countries.

Antibiotic therapy may have important side effects. Guidelines recommend the administration of specific probiotics to reduce the risk of antibiotic-associated diarrhoea (AAD). The rates and determinants of antibiotics and co-prescription of probiotics in children remain poorly known in Asia-Pacific countries, which are very heterogenous in terms of economic development, health care organization and health policies. A survey among general practitioners (GPs) and paediatricians was performed in seven countries of the Asia-Pacific area (Australia, Japan, Indonesia, India, China, Singapore, and South Korea). Physicians completed an online questionnaire that explored their current habits and the determinants for prescribing antibiotics and probiotics. For the 731 physicians who completed the questionnaire (390 paediatricians and 341 GPs), 37% of all consultations for a child led to the prescription of antibiotics (ranging from 17% in Australia to 47% in India). A large majority of physicians (84%) agreed that antibiotics disrupted gut microbiota and considered probiotics an effective intervention to prevent AAD (68%). However, only 33% co-prescribed probiotics with antibiotics (ranging from 13% in Japan to 60% in South Korea). The main reasons for prescribing probiotics were previous episodes of AAD (61%), presence of diarrhoea (55%), prolonged antibiotic treatment (54%) or amoxicillin-clavulanic acid therapy (54%). Although current local guidelines recommend the use of selected probiotics in children receiving antibiotics in Asia-Pacific area, the rates of antibiotics and probiotics prescription significantly vary among countries and are deeply affected by country-related cultural and organisational issues.

Identification of immunodominant VP1 linear epitope of enterovirus 71 (EV71) using synthetic peptides for detecting human anti-EV71 IgG antibodies in Western blots.

A major IgG-specific immunodominant VP1 linear epitope of enterovirus 71 (EV71) strain 41 (5865/SIN/00009), defined by the core sequence LEGTTNPNG, was identified by Pepscan analysis. Oligonucleotides corresponding to the amino-acid sequence of synthetic peptide SP32 were cloned and over-expressed in Escherichia coli as a recombinant glutathione-S-transferase (GST)-SP32 fusion protein. In ELISAs, this protein did not react with human anti-EV71 IgG antibodies, but there was significant immunoreactivity according to western blot analysis. The amino-acid sequence of SP32 was highly specific for detecting EV71 strains in western blot analysis, and showed no immunoreactivity with monoclonal antibodies raised against other enteroviruses, e.g., CA9 and Echo 6.

Outcome of liver transplantation for children with liver disease.

INTRODUCTION: The advent of liver transplantation has revolutionised the outcome of children with both acute liver failure and chronic end-stage liver disease. The aim of this study was to review the outcome of all paediatric liver transplants performed since the National Liver Transplant Programme began in 1990. METHODS: A retrospective review of all paediatric liver transplants from 1990 to December 2004 was performed. RESULTS: 46 liver transplants were performed in 43 children, of whom 23 (53.3 percent) were female. Median age at transplant was 21 months (range 11 months to 14 years). The most common indication for liver transplant was biliary atresia (71.7 percent). Living-related transplants accounted for 63 percent (29). Re-transplant rate was 6.5 percent with allograft loss as a result of hepatic artery thrombosis (two) and hepatic vein thrombosis (one). Tacrolimus was the primary immunosuppressive agent used in 89 percent of patients, with a 19.6 percent incidence of acute allograft rejection within the first six months. There were nine deaths. They were related to portal vein thrombosis (three), chronic rejection (one), sepsis (two), post-transplant lymphoproliferative disease (two) and primary graft non-function (one). Overall actuarial one- and five-year survival rate was 85.7 percent and 81.8 percent, respectively. CONCLUSION: Liver transplantation is an established form of intervention for end-stage liver disease and a variety of liver-related metabolic disease. Our results are comparable to those of well-established liver transplant centres.

Liver transplantation in Singapore 1990-2004.

INTRODUCTION: Liver transplantation is the accepted standard of care for patients with hepatocellular carcinoma, decompensated liver cirrhosis, and acute liver failure. Since the first liver transplant done in Singapore in 1990, results have been improving. We review the overall results of liver transplantation over the last 15 years. METHODS: All transplant cases from 1990 to 2004 were reviewed retrospectively. RESULTS: 100 liver transplants were performed over the last 15 years; four in the first five years and 96 in the subsequent ten years. Overall one- and five-year survival rates were 80 percent and 78 percent, respectively. 44 were paediatric transplants, of which biliary atresia was the commonest indication for paediatric transplant. 56 were adult transplants of which hepatocellular carcinoma and decompensated hepatitis B cirrhosis were the commonest indications for adult transplant. Infection remained the commonest cause of mortality. CONCLUSION: The number of transplants carried out per year was small due to the low cadaveric donation rate, but the survival of liver transplant patients was comparable to well-established liver transplant centres.

Referral patterns and waiting times for liver transplantation in Singapore.

INTRODUCTION: Referral patterns, waiting times, waiting list, and mortality provide information on how effectively a transplant programme deals with referred patients. This paper aims to review these parameters in the Singapore National Liver Transplant Programme. METHODS: Data of all patients referred to the Singapore National Liver Transplant Programme since its inception were captured and outcomes were retrieved and described. RESULTS: 562 patients were referred for liver transplant evaluation from 1990-2004, consisting of 457 adults and 105 children. The main indications for referral were hepatitis B liver disease and hepatocellular carcinoma in adults, and biliary atresia in children. Most patients were of United Network of Organ Sharing (UNOS) status 3 or 4 at the time of referral. 114 (20.28 percent) patients had transplants, consisting of 66 adults (14.44 percent) and 48 (45.71 percent) children. 138 adults and ten children were rejected for transplant, mainly for the reason of being "too early". The median waiting time for adults who had transplants was 3.3 months while adults still on the waiting list had been waiting for 16.2 months. The overall waiting list mortality was 44.3 percent, being 52.5 percent in adults and 23.2 percent in children. CONCLUSION: The overall transplantation rate is low and the waiting list mortality is high as a result of low availability of organs, particularly in adults. Paediatric liver transplant appears to have been better at dealing with referred patients but this is probably due to availability of living-related liver transplant. Improvement in these may result from the Human Organ Transplant Act.

A rotavirus vaccine for infants: the Asian experience.

INTRODUCTION: Severe rotavirus gastroenteritis in children causes significant morbidity worldwide and substantial deaths in developing countries. Hence, a live attenuated vaccine Rotarix was developed with human strain RIX4414 of G1P1A P[8] specificity. RIX4414 trials in infants have begun in developed and developing countries worldwide. An overview of RIX4414 in developed and developing countries and prospects with this vaccine in Asia are presented. METHODS: Completed RIX4414 trials have been reviewed. RESULTS: Two oral doses of RIX4414 were well tolerated with a reactogenicity profile similar to placebo. RIX4414 was also highly immunogenic, e.g., in a dose-ranging study conducted in Singapore, 98.8% to 100% of infants had a vaccine take after 2 doses. RIX4414 did not affect the immune response of simultaneously administered routine infant vaccines. RIX4414 significantly reduced severe rotavirus gastroenteritis in settings where multiple serotypes including the emerging G9 type co-circulated. CONCLUSION: These encouraging results warrant further evaluation of the vaccine worldwide and especially in developing countries with the highest need. Therefore, evaluation of the Rotarix vaccine is continuing in large phase III trials in Asia and worldwide.

Paediatrics in Singapore: the early days.

Paediatric services in Singapore started at the end of the 19th century. Because of inadequate housing, poor sanitation and inadequate health services, malnutrition and infections were the main problems. Infant mortality was in excess of 300/1000. There were many prominent doctors who worked in extremely demanding environments in order to better the health of children at that time. Over the years, there has been a steady improvement of healthcare in Singapore and this has been mainly due to the foresight and hard work of the pioneers. With excellent primary healthcare and specialised paediatric centres, paediatric services in Singapore are among the best in the world.

Two consecutive partial liver transplants in a patient with Classic Maple Syrup Urine Disease.

Maple syrup urine disease is caused by a deficiency in the branched chain ketoacid dehydrogenase (BCKAD) complex. This results in the accumulation of branched chain amino acids (BCAA) and branched chain ketoacids in the body. Even when aggressively treated with dietary restriction of BCAA, patients experience long term cognitive, neurological and psychosocial problems. Liver transplantation from deceased donors has been shown to be an effective modality in introducing adequate BCKAD activity, attaining a metabolic cure for patients. Here, we report the clinical course of the first known patient with classic MSUD who received two consecutive partial liver grafts from two different living non-carrier donors and his five year outcome posttransplant. We also show that despite the failure of the first liver graft, and initial acute cellular rejection of the second liver graft in our patient, his metabolic control remained good without metabolic decompensation.

Use of soy-protein formulas and soyfood for feeding infants and children in Asia.

Soybeans have been cultivated and consumed in Asia for many centuries. Soy products can be found in all households in Asian countries, and Asian children begin to consume soy formulas and soy products at a very young age. In a study of soy exposure in a group of healthy Singaporean children < 10 y of age, 70% had consumed soy products and of those > 95% had consumed soy products before the age of 18 mo. Soy products are commonly used as food flavorings and for weaning Asian children with lactose intolerance or allergy to cow-milk protein. The widespread use of soy formulas and soy products by Asian children is mainly due to the high nutritive value and palatability of these products.

PIP: Soybean cultivation and consumption in Asia dates back to 2838 BC with a documented evidence of soy farming between the 7th and 11th century. In most Asian countries soy products have become staples, which include soy cooking oil, soy flour, soy sauce, soy beverages, various forms of soybean curd (tofu) and soy infant formulas. A study conducted that evaluates the daily lactose intake among Singaporean children found that approximately 10% of the children were consuming soy formulas. This study examines the use of soy-protein formulas and soyfood for feeding infants and children in Asia. Results confirm the consumption of soy products by 90% of healthy Asian children, with 95% of these children consuming soyfood before 18 months of age. The use of tofu during weaning was more preferred by many Asian mothers because of its availability, soft consistency, high palatability, and high nutritional value. On the other hand, the use of soy formulas has been proven effective in treating children with lactose intolerance compared to cow-milk protein. Furthermore, the use of soy formulas was found to significantly reduce the prevalence of atopic diseases in the first 6 months of life, as well as for children with infantile atopic dermatitis, recurrent bronchiolitis, and bronchial asthma.

The nature of small bowel luminal fluid lactase.

The evidence indicating a mucosal source for the jejunal fluid lactase activity of children is so far inconclusive. Samples of jejunal mucosa and the adjacent fluid were obtained simultaneously from 15 children. Lactase activity was measured at pH 5.9 in mucosa and fluid. Fluid activities showed a significant positive correlation with the activity of the corresponding mucosal homogenate but a stronger correlation was found with an enterocyte microvillous membrane fraction prepared from the same homogenate (r = 0.807 and 0.889, respectively). Kinetic and pH optima studies were consistent with a microvillous membrane origin. Fluid activity and pH optimum were not changed detectably when measured in the presence of an enterocyte lysosomal acid lactase inhibitor. Jejunal fluid lactase activity and its properties closely reflect the microvillous membrane enzyme. Lysosomal acid lactase does not contribute measurably to the total lactase activity of jejunal fluid.

Role of glucose homeostatic mechanisms in viral infections.

Though normoglycaemia is thought to indicate adequacy of cellular glucose content, ketoacidosis occurs in viral infections even in the presence of normo- and hyperglycaemia. These wide variations in glucose concentrations may reflect the patients' adaptive abilities in situations where glucose transport is impaired by viruses. Hypoglycaemia would suggest poor adaptation and hyperglycaemia good adaptation. Increased free fatty acid (FFA) concentrations and enzyme activity are probable adaptive mechanisms. If so, they should decrease with hyperglycaemia-producing infusions. Profiles of glucose, FFA, enzymes, and fever over 19 days in 24 children with viral infections are reported. On admission 87.5% were normo- or hyperglycaemic with increased FFA, AST, LDH, and fever (P less than 0.005) when compared with values 19 days later. With infusions that produced hyperglycaemia, there was clinical recovery with a decrease in FFA and enzyme activity. The hyperglycaemia observed in 56.5% therefore points to glucose homeostatic mechanisms being geared to maintain the intracellular milieu. Hence normoglycaemia does not always indicate cellular glucose adequacy.

Successful listing of patients for liver transplant was related to participation of referring doctor in the transplant program.

INTRODUCTION: Experience with liver transplantation is limited in many parts of Asia. Therefore, patients from nontransplant centers may not be referred in a timely fashion for transplants. Our aim was to evaluate the pattern of referral for liver transplantation and their outcomes in Singapore. METHODS: Consecutive patients referred from 1990 to 2001 were reviewed. Patients from any hospital in Singapore (or the region) could be referred to the program. They were discussed at the weekly meetings. Appropriate patients were placed on the waiting list. "Pending" indicated that the disease was early or there were unsettled medical or social issues. Unsuitable patients were "rejected" for transplant. RESULTS: There were 385 patients referred over a 12-year period. Hepatitis B cirrhosis and hepatocellular carcinoma (HCC) were the most common indications among adults, whereas biliary atresia was the most common for children. Pediatric patients were more likely than adult patients to be listed for transplant (53/76 vs 106/309, P < .001). Patients referred by regular attendees of the program were more likely to be accepted than nonattendees (38% vs 25%, P = .04). "Disease too early", "advanced HCC", and "refusal by family members" were the most common reasons for rejection. CONCLUSION: Members of the Liver Transplant Program were more likely to refer suitable patients for transplant at the appropriate time. Better interaction between gastroenterologists inside and outside the transplant program would help to improve the timing of referrals for liver transplantation, and hence, patient survival.

Renal impairment and diabetes mellitus after liver transplant.

INTRODUCTION: One of the major concerns in liver transplant patients who survive past 1 year posttransplant is the development of chronic diseases. AIM: We studied two important clinical conditions that can have a chronic course-renal impairment and diabetes mellitus-among long-term liver transplant survivors. METHODS: All adult patients transplanted and followed for at least 1 year were evaluated for clinical status, blood tests, and imaging studies. The occurrence and development of renal impairment, defined as a serum creatinine above 125 micromol/L or creatinine clearance less than 75 mL/min, or diabetes mellitus were evaluated for contributing factors. RESULTS: The 35 evaluated patients of mean age at transplant of 50 years had a mean follow-up duration of 45 months. The incidence of posttransplant renal impairment was 22.8% at 1 year and 47.6% at 3 years. This disorder was associated with pretransplant renal impairment and with a diagnosis of diabetes. Posttransplant diabetes mellitus was observed in 48.6% with 41.1% resolving over time. CONCLUSION: Posttransplant renal impairment appears to be a potential long-term problem. Although this relates to pretransplant conditions, longer follow-up is required to examine whether posttransplant factors contribute to its progression.

Persistent thrombocytopenia in liver transplant patients.

INTRODUCTION: The occurrence of thrombocytopenia in the perioperative period after a liver transplant is not uncommon. However, there are few studies on persistent thrombocytopenia during the longer follow up period of patients after liver transplantation. We examined the prevalence of and contributing factors to persistent thrombocytopenia beyond 1 year post-liver transplantation. METHODS: We analyzed adult patients followed for at least 1 year posttransplant with full blood counts and abdominal scans, as well as clinical notes. RESULTS: The 35 patients of mean age at transplant of 50 years and showed a mean follow-up of about 4 years showed a prevalence of persistent thrombocytopenia at 12 months of 54% and at 3 years of 25%. Factors that were associated with persistent thrombocytopenia were pretransplant variceal bleeding, splenomegaly, and thrombocytopenia at 3 and 6 months posttransplant. After multivariate analysis only the latter represented independent factors for persistent thrombocytopenia at 1 and 3 years posttransplant, respectively. CONCLUSION: Persistent thrombocytopenia improved over time posttransplant; no bleeding problem was observed among the affected cases.

Esophageal intramural pseudodiverticulosis associated with a web in a 12-year-old boy.

Esophageal intramural pseudodiverticulosis (EIPD) is a rare benign disorder characterized by dilation of the submucosal glands. Its etiology and pathogenesis are largely unknown. So far, less than 10 pediatric cases of EIPD have been reported. The authors present the case of a 12-year-old boy with EIPD that was associated with a cervical esophageal web. He was treated successfully with dilation therapy.

Neonatal total gastrectomy.

A 2-day-old, female infant underwent total gastrectomy for spontaneous gastric gangrene and perforation. She developed the following complications: growth retardation, vitamin B12 deficiency, post-gastrectomy dumping syndrome, and occasional bile regurgitation. Nutritional management is described. The two previously reported survivors of total gastrectomy in the neonatal period are reviewed.

Colonoscopy in children with bleeding per rectum.

There are few reports of colonoscopy in children. Twenty-six children with bleeding per rectum were examined colonoscopically to determine the aetiology of the bleeding. A total of 32 colonoscopies were performed. Except for 5 children who needed general anaesthesia, all the rest were performed with pethidine and diazepam sedation. The mean age of these 26 children was 63.5 months (SD 57.5 months, range 2 weeks to 180 months). Ten children had histologically confirmed colitis. Five had bleeding juvenile polyps and these were removed endoscopically. One had lymphoid hyperplasia and one had chronic solitary sigmoid ulcer. The rest were normal. It is concluded that colonoscopy can be performed safely in children and it is a good diagnostic and therapeutic procedure.