Acute liver failure secondary to niacin toxicity.

A 17-year-old male was transferred to the pediatric intensive care unit for evaluation of acute liver failure. He was recently released from an alcohol treatment center with acute onset of chest pain. Cardiac workup was negative but he was found to have abnormal coagulation studies and elevated liver transaminases. Other evaluations included a normal toxicology screen and negative acetaminophen level. Autoimmune and infectious workups were normal providing no identifiable cause of his acute liver failure. He initially denied any ingestions or illicit drug use but on further query he admitted taking niacin in an attempt to obscure the results of an upcoming drug test. Niacin has been touted on the Internet as an aid to help pass urine drug tests though there is no evidence to support this practice. Niacin toxicity has been associated with serious multisystem organ failure and fulminant hepatic failure requiring liver transplantation. Pediatric providers should be aware of the risks associated with niacin toxicity and other experimental medical therapies that may be described on the Internet or other nonreputable sources.

Congenital heart disease and the liver.

There are approximately 1 million adult patients with congenital heart disease (CHD) in the United States, and the number is increasing. Hepatic complications are common and may occur secondary to persistent chronic passive venous congestion or decreased cardiac output resulting from the underlying cardiac disease or as a result of palliative cardiac surgery; transfusion or drug-related hepatitis may also occur. The unique physiology of Fontan circulation is particularly prone to the development of hepatic complications and is, in part, related to the duration of the Fontan procedure. Liver biochemical test abnormalities may be related to cardiac failure, resulting from intrinsic liver disease, secondary to palliative interventions, or drug related. Complications of portal hypertension and, rarely, hepatocellular carcinoma (HCC) may also occur. Abnormalities such as hypervascular nodules are often observed; in the presence of cirrhosis, surveillance for HCC is necessary. Judicious perioperative support is required when cardiac surgery is performed in patients with advanced hepatic disease. Traditional models for liver disease staging may not fully capture the severity of disease in patients with CHD. The effectiveness or safety of isolated liver transplantation in patients with significant CHD is limited in adults; combined heart-liver transplantation may be required in those with decompensated liver disease or HCC, but experience is limited in the presence of significant CHD. The long-term sequelae of many reparative cardiac surgical procedures are not yet fully realized; understanding the unique and diverse hepatic associations and the role for early cardiac transplantation in this population is critical. Because this population continues to grow and age, consideration should be given to developing consensus guidelines for a multidisciplinary approach to optimize management of this vulnerable population.

An unusual presentation of a congenital intrahepatic arterioportal fistula in an infant with Down syndrome.

Congenital intrahepatic arterioportal fistula is a rare entity that most often presents with symptoms of portal hypertension and malabsorption. We discuss a patient who presented with distributive shock, congestive heart failure, pulmonary hypertension, ascites, and a history of severe constipation.

Liver transplantation for pulmonary vascular complications of pediatric end-stage liver disease.

PURPOSE: Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH) are poorly understood pulmonary complications of end-stage liver disease (ESLD). We present a case series of children with HPS and PPH. METHODS: After institutional review board approval, query of our medical database identified children 0 to 18 years of age with ESLD diagnosed with HPS or PPH. Data were collected via chart review. RESULTS: We identified 7 children with either HPS (n = 5) or PPH (n = 2). Patients with HPS presented with progressive dyspnea over a mean of 7 months (range, 4-12 months) at a mean of 13 years (range, 5-17 years) of age. Pulmonary shunting by albumin perfusion scan averaged 41% (range, 20%-66%) with an initial mean resting SpO(2) of 88% (range, 84%-94%) and mean SpO(2) during exertion of 79% (range, 60%-89%). Four patients required supplemental O(2) and, upon United Network for Organ Sharing (UNOS) appeal, received pediatric model for ESLD (or Child-Pugh) score exceptions, enabling them to undergo orthotopic liver transplant (OLT) within 1-2 months. The fifth patient was initially rejected by the UNOS regional review board, but 6 months of worsening hypoxemia led to OLT 2 months after successful UNOS appeal. All patients with HPS undergoing OLT experienced complete resolution of hypoxemia within 8 months. Both children with PPH were treated with intravenous epoprostenol, which lowered or stabilized mean pulmonary artery pressure and bridged them to OLT within 7 months of listing. Overall, there were no pulmonary complications; however, 1 patient with PPH expired shortly after OLT. The remaining patients are alive at a median follow-up of 27 months (range, 6-96 months). CONCLUSION: Hepatopulmonary syndrome and PPH are uncommon complications of ESLD in children. Epoprostenol can bridge PPH patients to OLT. OLT leads to rapid resolution of HPS and PPH and currently represents the only successful treatment for these children.

Significance of central perivenulitis in pediatric liver transplantation.

Central perivenulitis (CP) encompasses dropout of zone 3 hepatocytes, red blood cell extravasation, and perivenular mononuclear inflammation. In the liver transplant setting, CP can occur in isolation or it can occur in association with portal-based disease such as acute cellular rejection (PB-ACR). Some CP is also thought to be a manifestation of chronic rejection, particularly when accompanied by zone 3 fibrosis. Prior studies of CP in pediatric liver allografts have been hampered by lack of protocol biopsies and low rates of histologic follow-up. We studied 62 consecutive liver allografts from 55 pediatric patients (age: < or =18 y) who underwent transplant from the years 1995 to 2007. Forty-nine allografts (79%) had > or =1 year of histologic follow-up, 32 (52%) > or =3 years, and 24 (39%) > or =5 years. We reviewed a total of 445 allograft biopsies (mean: 7.2 per allograft) obtained at 2 days to 11 years; 213 (48%) of these were protocol biopsies. Seven explanted livers that were removed during the course of retransplantation for graft failure in this group were also reviewed. All specimens were scored for the following features: (1) CP (mild, moderate, and severe), (2) portal ACR (mild, moderate, and severe), (3) zone 3 fibrosis (mild=perivenular or severe=bridging), and (4) ductopenia. CP was present in 120 (27%) of 445 biopsies, including 73 with CP+PB-ACR, 16 with CP within 1 month of PB-ACR, 27 with isolated CP, 3 with CP+de-novo autoimmune hepatitis, and 1 with CP+Epstein-Barr virus infection. Overall, CP was observed on at least 1 occasion in 41 (66%) allografts. It was not associated with any specific liver function test abnormality or pattern of liver function test abnormalities, it was not associated with vascular compromise as judged by Doppler ultrasound examinations, and it was not related to type of immunosuppression. CP overall was equally prevalent in the early (< or =3 mo) and late (>3 mo) post-transplant periods, but isolated CP increased in the late period. On follow-up, 6 (15%) of 41 allografts with CP developed ductopenic chronic rejection (4 requiring retransplantation) and 10 (25%) developed zone 3-based fibrosis without ductopenia (2 severe, 8 mild). In contrast, none of the 21 allografts without CP developed chronic rejection (P=0.09) and none had zone 3-based fibrosis on their last biopsy (P<0.001). All patients who developed ductopenia had 1 or more episodes of CP+PB-ACR. In contrast, isolated CP [seen in 17 (27%) allografts on at least 1 occasion] was associated with zone 3-based fibrosis in 50%, but did not lead to ductopenic chronic rejection. These results underscore the high frequency of CP in pediatric liver transplantation, occurring in 27% of all allograft biopsies and 66% of allografts overall. CP is most common in conjunction with portal ACR, where it carries a significant risk for the development of zone 3 fibrosis and a trend toward the development of ductopenic chronic rejection.

A population-based study of the frequency of corticosteroid resistance and dependence in pediatric patients with Crohn's disease and ulcerative colitis.

BACKGROUND: The goal of this study was to examine the 1-year outcome after the first course of systemic corticosteroids in an inception cohort of pediatric patients with inflammatory bowel disease. METHODS: All Olmsted County (Minnesota) residents diagnosed with Crohn's disease (n = 50) or ulcerative colitis (n = 36) before 19 years of age from 1940 to 2001 were identified. Outcomes at 30 days and 1 year after the initial course of corticosteroids were recorded. RESULTS: Twenty-six patients with Crohn's disease (65%) and 14 with ulcerative colitis (44%) were treated with corticosteroids before age 19. Thirty-day outcomes for corticosteroid-treated Crohn's disease were complete remission in 16 (62%), partial remission in 7 (27%), and no response in 3 (12%), with 2 of these patients requiring surgery. Thirty-day outcomes for treated ulcerative colitis were complete remission in 7 (50%), partial remission in 4 (29%), and no response in 3 (21%). One-year outcomes for Crohn's disease were prolonged response in 11 (42%) and corticosteroid dependence in 8 (31%), whereas 7 (27%) were postsurgical. One-year outcomes for ulcerative colitis were prolonged response in 8 (57%) and corticosteroid dependence in 2 (14%), whereas 4 (29%) were postsurgical. CONCLUSIONS: Most pediatric patients with inflammatory bowel disease initially responded to corticosteroids. However, after 1 year, 58% of pediatric patients with Crohn's disease and 43% of pediatric patients with ulcerative colitis either were steroid dependent or required surgery. This finding emphasizes the need for early steroid-sparing medications in pediatric inflammatory bowel disease.

Clinical characteristics of eosinophilic esophagitis in children.

OBJECTIVES: The role of eosinophilic esophagitis (EE) in aerodigestive tract disorders in children is underestimated and overlooked, primarily because of a lack of understanding of this disorder by otolaryngologists. We sought to better characterize the clinical presentation of EE in order to increase awareness among otolaryngologists. METHODS: We retrospectively reviewed 71 children with biopsy-proven EE to determine the most common symptoms and laboratory findings that should increase the clinical suspicion of EE. RESULTS: Dysphagia, food impaction, and emesis were the most common symptoms in children with EE. Asthma was the most common airway diagnosis. Rhinosinusitis was the most common otolaryngological diagnosis. Food allergy was present in 60% of the children tested. Eighty-three percent of the children with elevated immunoglobulin E levels had thick linear streaking or patchy white exudate of the esophagus seen on esophagoscopy. Other major medical comorbidities existed in more than half of the children with EE, of which psychiatric disorders and other disorders of the aerodigestive tract were the most common. CONCLUSIONS: Eosinophilic esophagitis may contribute to treatment failure in patients with common and complicated aerodigestive tract disorders. To encourage clinicians to avoid overlooking the diagnosis, we present an evaluative algorithm to increase the suspicion of this entity.

Guideline for the evaluation of cholestatic jaundice in infants: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

For the primary care provider, cholestatic jaundice in infancy, defined as jaundice caused by an elevated conjugated bilirubin, is an uncommon but potentially serious problem that indicates hepatobiliary dysfunction. Early detection of cholestatic jaundice by the primary care physician and timely, accurate diagnosis by the pediatric gastroenterologist are important for successful treatment and a favorable prognosis. The Cholestasis Guideline Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition has formulated a clinical practice guideline for the diagnostic evaluation of cholestatic jaundice in the infant. The Cholestasis Guideline Committee, consisting of a primary care pediatrician, a clinical epidemiologist (who also practices primary care pediatrics), and five pediatric gastroenterologists, based its recommendations on a comprehensive and systematic review of the medical literature integrated with expert opinion. Consensus was achieved through the Nominal Group Technique, a structured quantitative method. The Committee examined the value of diagnostic tests commonly used for the evaluation of cholestatic jaundice and how those interventions can be applied to clinical situations in the infant. The guideline provides recommendations for management by the primary care provider, indications for consultation by a pediatric gastroenterologist, and recommendations for management by the pediatric gastroenterologist. The Cholestasis Guideline Committee recommends that any infant noted to be jaundiced at 2 weeks of age be evaluated for cholestasis with measurement of total and direct serum bilirubin. However, breast-fed infants who can be reliably monitored and who have an otherwise normal history (no dark urine or light stools) and physical examination may be asked to return at 3 weeks of age and, if jaundice persists, have measurement of total and direct serum bilirubin at that time. This document represents the official recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition on the evaluation of cholestatic jaundice in infants. The American Academy of Pediatrics has also endorsed these recommendations. These recommendations are a general guideline and are not intended as a substitute for clinical judgment or as a protocol for the care of all patients with this problem.

Primary sclerosing cholangitis in children: a long-term follow-up study.

Primary sclerosing cholangitis (PSC) is increasingly diagnosed in children and adolescents, but its long-term prognosis remains uncertain. The aim of this longitudinal, cohort study was to determine the long-term outcome of children with PSC. Fifty-two children with cholangiography-proven PSC (34 boys and 18 girls; mean age 13.8 +/- 4.2 years; range, 1.5-19.6 years) who were seen at our institution over a 20-year period were followed-up for up to 16.7 years. Two thirds presented with symptoms and/or signs of PSC and 81% had concomitant inflammatory bowel disease (IBD). Twenty-five percent had total alkaline phosphatase activity within the normal range for the age group, but all of them had elevated gamma-glutamyl transpeptidase levels. Autoimmune hepatitis overlapping with PSC was present in 35% of children. A positive but transient clinical and/or biochemical response occurred under therapy with ursodeoxycholic acid, alone or in combination with immunosuppressive medications. During follow-up, 11 children underwent liver transplantation for end-stage PSC and 1 child died. The median (50%) survival free of liver transplantation was 12.7 years. Compared with an age- and gender-matched U.S. population, survival was significantly shorter in children with PSC (P <.001). In a Cox regression model, lower platelet count, splenomegaly, and older age were associated with shorter survival. Presence of autoimmune hepatitis overlapping with PSC (P =.2) or medical therapy (P =.2) did not affect survival. In conclusion, PSC significantly decreases survival in this child population. Although pharmacologic therapy may improve symptoms and liver test results initially, it does not seem to impact the long-term outcome.

Prevalence and clinical significance of human herpesviruses 6 and 7 active infection in pediatric liver transplant patients.

Recent studies in adult liver transplant patients have suggested that both human herpesvirus (HHV)-6 and HHV-7 infection are important causes of morbidity following liver transplantation. However, the impact of HHV-6 and -7 infection in pediatric liver transplant patients remains largely unknown. The aims were to determine the prevalence of HHV-6 and -7 infection in pediatric liver transplant patients and to determine whether there is an association between HHV-6 and -7 infection with episodes of graft rejection and cytomegalovirus (CMV) infection. A total of 46 pediatric liver transplant patients transplanted at Mayo Clinic between January 1994 and January 2000 were evaluated. Quantitative polymerase chain reaction (PCR) assays for CMV, HHV-6 and HHV-7 were performed on stored sera obtained prior to transplant, weekly for 8 wk and at 4 months and 1 yr post-transplant. Pretransplant sera were tested for HHV-6 antibodies by indirect immunofluorescence assay. A total of 215 blood samples were tested (mean 6.5 +/- 3.1, range 3-18). CMV infection occurred in 11 of 33 (33.3%) patients, while CMV disease occurred in 4 of 33 (12%) patients. Infection with HHV-6 (variant B) was detected in three of 33 (9.1%) patients. HHV-7 infection was not detected. Case 1 and 2 were infants (10- and 11-month old, respectively). Both were seronegative for HHV-6 pretransplant. In both cases, HHV-6 infection was associated with concurrent episodes of moderate to severe acute graft rejection. Case 3 was a 16-yr-old girl who was seropositive for HHV-6 pretransplant. No clinical events were recorded and a liver biopsy performed per protocol showed no evidence of rejection. None of the three patients had concomitant CMV infection or disease. In this study, HHV-6 infection occurred in 9% of pediatric liver transplant patients while HHV-7 was not detected. A potential association between primary HHV-6 infection and allograft rejection warrants further investigation.