Biliary Excretion Noted on Hepatobiliary Iminodiacetic Acid Scan Does Not Exclude Diagnosis of Biliary Atresia.

A hepatobiliary iminodiacetic acid (HIDA) scan is frequently used in an attempt to exclude biliary atresia in infants who are cholestatic. We present 6 cases of confirmed biliary atresia in infants who had biliary patency reported on HIDA scan. We demonstrate that misinterpreted HIDA scans led to delayed diagnosis and surgical intervention for biliary atresia.

Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis: Predictors of Gamma Glutamyltransferase Normalization and Favorable Clinical Course.

OBJECTIVE: To investigate patient factors predictive of gamma glutamyltransferase (GGT) normalization following ursodeoxycholic acid (UDCA) therapy in children with primary sclerosing cholangitis. STUDY DESIGN: We retrospectively reviewed patient records at 46 centers. We included patients with a baseline serum GGT level ≥50 IU/L at diagnosis of primary sclerosing cholangitis who initiated UDCA therapy within 1 month and continued therapy for at least 1 year. We defined "normalization" as a GGT level <50 IU/L without experiencing portal hypertensive or dominant stricture events, liver transplantation, or death during the first year. RESULTS: We identified 263 patients, median age 12.1 years at diagnosis, treated with UDCA at a median dose of 15 mg/kg/d. Normalization occurred in 46%. Patients with normalization had a lower prevalence of Crohn's disease, lower total bilirubin level, lower aspartate aminotransferase to platelet ratio index, greater platelet count, and greater serum albumin level at diagnosis. The 5-year survival with native liver was 99% in those patients who achieved normalization vs 77% in those who did not. CONCLUSIONS: Less than one-half of the patients treated with UDCA have a complete GGT normalization in the first year after diagnosis, but this subset of patients has a favorable 5-year outcome. Normalization is less likely in patients with a Crohn's disease phenotype or a laboratory profile suggestive of more advanced hepatobiliary fibrosis. Patients who do not achieve normalization could reasonably stop UDCA, as they are likely not receiving clinical benefit. Alternative treatments with improved efficacy are needed, particularly for patients with already-advanced disease.

Corticosteroid Therapy for Indeterminate Pediatric Acute Liver Failure and Aplastic Anemia with Acute Hepatitis.

OBJECTIVE: To examine the characteristics and outcomes of a multicenter patient cohort with indeterminate pediatric acute liver failure (IND-PALF) and with aplastic anemia with acute hepatitis treated with corticosteroids. STUDY DESIGN: Retrospective study of patients age 1-17 years with IND-PALF and aplastic anemia with acute hepatitis who presented between 2009 and 2018 to 1 of 4 institutions and were treated with corticosteroids for presumed immune dysregulation. RESULTS: Of 28 patients with IND-PALF (median of 4.0 years of age [range 1-16] and 71% male) 71% (n = 20) were treated with 0.5-4 mg/kg/day of intravenous methylprednisolone, and 8 patients received 10 mg/kg/day followed by a taper. By 21 days postcorticosteroid initiation, 14 patients (50%) underwent liver transplantation, 13 patients (46%) recovered with their native liver, and 1 patient (4%) died. Patients who recovered with their native liver received a median of 139 days (range 19-749) of corticosteroid therapy, with a median of 12 days (range 1-240) to international normalized ratio ≤1.2. Patients with aplastic anemia with acute hepatitis (n = 6; median of 9.5 years of age [range 1-12], 83% male), received 1-2 mg/kg/day of methylprednisolone for a median of 100 days (range 63-183), and all recovered with their native liver. One patient with IND-PALF and 2 patients with aplastic anemia with acute hepatitis developed a serious infection within 90 days postcorticosteroid initiation. CONCLUSIONS: Many patients with IND-PALF or aplastic anemia with acute hepatitis that were treated with corticosteroids improved, but survival with native liver may not be different from historical reports. A randomized controlled trial exploring the benefits and risks of steroid therapy is needed before it is adopted broadly.

Steroid Free Treatment of Autoimmune Hepatitis in Selected Children.

Current guidelines recommend steroids for induction of remission in all children diagnosed with autoimmune hepatitis regardless of the clinical presentation. In this report, we describe our experience in treating selected asymptomatic children with autoimmune hepatitis using a steroid-free regimen; this treatment strategy was safe and effective in inducing remission.

Splenic Rupture in Children With Portal Hypertension.

INTRODUCTION: Massive splenomegaly from portal hypertension (PHTN) in children raises the specter of splenic rupture; however, the incidence, etiology, and risk of rupture have not been studied, nor have existing practices to reduce risk. We therefore performed an international survey to describe the splenic rupture cases in PHTN and to describe the existing empirical practice among hepatologists. METHODS: A questionnaire was constructed to elicit cases of splenic rupture and collect hepatologists' common practices for prevention of splenic rupture. Pediatric hepatologists working in selected tertiary academic centers in the United States, Canada, and the United Kingdom were contacted. RESULTS: Hepatologists from 30 of 35 centers who met the inclusion criteria replied to the survey. Thirteen cases of splenic rupture were described of which 11 resulted from trauma. In the opinion of the practitioners, high-risk activities were football, hockey, and wrestling. Sixty-one percent recommended total restriction from high-risk activities. Seventy-four percent stated that platelet count had no effect on this decision and 61% advised a spleen guard for certain activities. CONCLUSIONS: Splenic rupture in patients with PHTN and splenomegaly seems to be rare. The reported splenic rupture cases were mostly related to falling (and not to participation in sports). There was general agreement among hepatologists about restricting high impact sports. There was variation in recommendations regarding the use of a spleen guard. The authors recommend use of spleen guards in children with splenomegaly from PHTN for physical activities with risk of fall or blunt abdominal trauma.

Frailty in Children with Liver Disease: A Prospective Multicenter Study.

OBJECTIVE: To assess frailty, a measure of physiologic declines in multiple organ systems, in children with chronic liver disease using a novel pediatric frailty tool. STUDY DESIGN: We performed a prospective cross-sectional multicenter study at 17 liver transplantation (LT) centers. 71 children (5-17 years of age), 36 with compensated chronic liver disease (CCLD) and 35 with end-stage liver disease (ESLD) and listed for LT, were assessed for frailty using validated pediatric tools to assess the 5 classic Fried Frailty Criteria-slowness, weakness, exhaustion, diminished physical activity, and shrinkage. Test scores were translated to age- and sex-dependent z scores, generating a maximum frailty score of 10. RESULTS: The median frailty score of the cohort was 4 (IQR 3, 5). Subjects with ESLD had significantly higher frailty scores (median 5; IQR 4, 7) than subjects with CCLD (median 3; IQR 2, 4); (P < .0001). Area under the curve receiver operating characteristic for frailty scores to discriminate between ESLD and CCLD was 0.83 (95% CI 0.73, 0.93). Forty-six percent of children with ESLD were frail and there was no correlation between pediatric frailty scores and physician's global assessments (r = -0.24, 95% CI -0.53, 0.10). CONCLUSIONS: A novel frailty tool assessed additional dimensions of health, not captured by standard laboratory measures and identified the sickest individuals among a cohort of children with chronic liver disease. This tool may have applicability to other children with chronic disease.

Using Maslow's hierarchy to highlight power imbalances between visiting health professional student volunteers and the host community: An applied qualitative study.

BACKGROUND: Health professional students from high-income countries increasingly participate in short-term experiences in global health (STEGH) conducted abroad. One common criticism of STEGH is the inherent power differential that exists between visiting learners and the local community. To highlight this power differential, this paper explores perceived benefits as described by volunteer and community respondents and applies Maslow's hierarchy of needs to commonly identified themes in each respondent group. METHODS: A semistructured survey was used to collect qualitative responses from both volunteers and community members located in a Dominican Republic community, that is, a hotspot for traditionally conducted STEGH. Thematic analysis identified themes of perceived benefits from both respondent groups; each group's common themes were then classified and compared within Maslow's hierarchy of needs. RESULTS: Each respondent group identified resource provision as a perceived benefit of STEGH, but volunteer respondents primarily focused on the provision of highly-skilled, complex resources while community respondents focused on basic necessities (food, water, etc.) Volunteer respondents were also the only group to also mention spiritual/religious/life experiences, personal skills development, and relationships as perceived benefits. Applying Maslow's hierarchy thus demonstrates a difference in needs: community respondents focused on benefits that address deficiency needs at the bottom of the hierarchy while volunteers focused on benefits addressing self-transcendence/actualization needs at the top of the hierarchy. CONCLUSIONS: The perceived difference in needs met by STEGH between volunteers and the host community within Maslow's hierarchy may drive an inherent power differential. Refocusing STEGH on the relationship level of the hierarchy (i.e., focusing on partnerships) might help mitigate this imbalance and empower host communities.

Hepatic Fibrosis Is Universal Following Fontan Operation, and Severity is Associated With Time From Surgery: A Liver Biopsy and Hemodynamic Study.

BACKGROUND: Congestive hepatopathy is a recognized complication of Fontan physiology. Data regarding the incidence of hepatopathy and risk factors are lacking. METHODS AND RESULTS: Liver biopsies and cardiac catherizations were performed as part of an evaluation offered to all patients ≥10 years after Fontan. Quantitative determination of hepatic fibrosis was performed using Sirius red staining with automated calculation of collagen deposition per slide (%CD). Biopsies from included subjects were compared to stained specimens from controls without known fibrotic liver disease. Patient characteristics, echocardiographic findings, and hemodynamic measures were evaluated as potential risk factors. The cohort consisted of 67 patients (31 female) at mean age of 17.3±4.5 years and mean time from Fontan of 14.9±4.5 years. Right ventricular morphology was present in 37 subjects. Median %CD by Sirius red staining was 21.6% (range 8.7% to 49.4%) compared to 2.6% (range 2.2% to 3.0%) in controls. There was a significant correlation between time from Fontan and degree of Sirius red staining (r=0.33, P<0.01). Serum liver enzymes and platelet count did not correlate with %CD. The median inferior vena cava pressure was 13 mm Hg (range 6-24 mm Hg) and did not correlate with %CD. There was no difference in %CD based on ventricular morphology or severity of atrioventricular valve insufficiency. CONCLUSIONS: In this cohort of predominantly asymptomatic children and adolescents electively evaluated after a Fontan operation, all exhibited evidence for hepatic fibrosis as measured by collagen deposition in the liver. Time from Fontan was the only factor significantly associated with collagen deposition. These findings demonstrate that liver fibrosis is an inherent feature of Fontan physiology and that the degree of fibrosis increases over time.

Health and Social Needs in Three Migrant Worker Communities around La Romana, Dominican Republic, and the Role of Volunteers: A Thematic Analysis and Evaluation.

Objective. For decades, Haitian migrant workers living in bateyes around La Romana, Dominican Republic, have been the focus of short-term volunteer medical groups from North America. To assist these efforts, this study aimed to characterize various health and social needs that could be addressed by volunteer groups. Design. Needs were assessed using semistructured interviews of community and professional informants, using a questionnaire based on a social determinants of health framework, and responses were qualitatively analysed for common themes. Results. Key themes in community responses included significant access limitations to basic necessities and healthcare, including limited access to regular electricity and potable water, lack of health insurance, high out-of-pocket costs, and discrimination. Healthcare providers identified the expansion of a community health promoter program and mobile medical teams as potential solutions. English and French language training, health promotion, and medical skills development were identified as additional strategies by which teams could support community development. Conclusion. Visiting volunteer groups could work in partnership with community organizations to address these barriers by providing short-term access to services, while developing local capacity in education, healthcare, and health promotion in the long-term. Future work should also carefully evaluate the impacts and contributions of such volunteer efforts.

Sexual health knowledge in a vulnerable population: a survey of adolescents in the bateyes of La Romana, Dominican Republic.

OBJECTIVE: Undocumented Haitian migrants to the Dominican Republic often live in impoverished communities called bateyes. These contexts present challenges for adolescent sexual health education. To inform development of appropriate adolescent education programs, this study assessed their general sexual health knowledge. METHODS: A locally developed sexual health knowledge survey was administered to 930 grade 7-12 adolescents attending six batey schools. Analysis of aggregated responses reviewed general demographics (e.g. age and sex), and identified top community sexual health concerns and most trusted information sources. RESULTS: Top concerns included menstruation (25.5%), HIV (21.8%), and family planning (13.3%); stratification by sex identified discordance around menstruation (89.2% female, 10.8% male) and HIV (67.1% male, 32.9% female), but not family planning (47.2% male, 52.8% female). Parents were identified as the most trusted information source, irrespective of concern. CONCLUSION: Community concerns around menstruation matches extant developing-world literature that links menarche with female stigma and school absence. Interest in HIV and family planning suggests targeted promoted efforts would be of benefit. Trust in parents is reflective of cultural traditions and suggests potential knowledge impacts arising from effective parental education.

Clinical guidelines for Western clinicians engaged in primary care medical service trips in Latin America and the Caribbean: an integrative literature review.

OBJECTIVE: Participation in primary care-focused medical service trips (MSTs) by North American providers is increasingly common, with many of these being conducted in Latin America. The literature has yet to comprehensively explore the nature of MST practice, including the use of evidence-based clinical guidelines. This integrative review presents an analysis of guidelines employed in MSTs in Latin America. METHODS: MEDLINE and LILACs were searched using the terms 'medical brigades', 'Latin America', 'primary health care' and related terms. The search was limited to articles published between 2000 and 2015 in any language. Qualitative or quantitative articles were subsequently included if they described management protocols in the context of patient care on an MST occurring in Latin America. Additional publications were identified by searching the citations of articles reviewed in full. Themes were extracted to an Excel file, and objective instruments were used to evaluate article quality (Mixed Methods Assessment Tool) and the quality of guidelines (Appraisal of Guidelines for Research & Evaluation II). RESULTS: Of 391 abstracts screened, eight met inclusion criteria. All described MSTs operating in rural settings in Central America. Five were qualitative descriptive, including two travel reports, an ethics thesis paper, and a description of a dermatologic MST. Four described subjective clinician experiences while describing non-evidence-based treatment suggestions or practices. Only one described evidence-supported primary care interventions. Three studies were quantitative descriptive, including two epidemiological articles, one of which used case definitions for select diagnoses. One described the application of American Family Physician guidelines to the description of UTI prevalence on a MST. Article scores in MMAT quality domains were variable, and only one article achieved a positive overall AGREE II score for guideline quality. CONCLUSIONS: Existing literature demonstrates minimal development or use of clinical guidelines on MSTs in Latin America. Future work must focus on the development, implementation, and evaluation of culturally sensitive, evidence-based guidelines for the management of patients receiving care from MSTs.

Resolution of Hepatic Artery Thrombosis in 2 Pediatric Liver Transplant Patients.

Hepatic artery thrombosis (HAT) is a serious complication after liver transplantation. This is the first report of spontaneous resolution of HAT in pediatric liver transplant patients on low molecular weight heparin therapy. A total of 2 patients, a 26-month-old boy who presented with acute liver failure and required emergent liver transplantation and a 15-year-old boy with ulcerative colitis and autoimmune hepatitis-primary sclerosing cholangitis overlap underwent liver transplantation for progressive cirrhosis; both developed HAT during the postoperative period. They were both treated with low molecular weight heparin. Follow-up imaging for both patients showed resolution of HAT without evidence of collateral flow.

Sertraline-Associated Cholestasis and Ductopenia Consistent with Vanishing Bile Duct Syndrome.

An adolescent with depression treated with sertraline developed cholestasis and bile duct paucity, which resolved with medication discontinuation. Vanishing bile duct syndrome is an acquired destruction of interlobular bile ducts. This type of drug-induced liver injury has been associated with other medications and requires practitioners' awareness of potential hepatotoxicity.

Short-term global health education programs abroad: disease patterns observed in Haitian migrant worker communities around La Romana, Dominican Republic.

The possibility of encountering rare tropical disease presentations is commonly described as a benefit derived by developed world medical trainees participating in clinical service-oriented short-term global health experiences in the developing world. This study describes the health status of a population served by a short-term experience conducted by a North American institute, and the results of a retrospective review are used to identify commonly encountered diseases and discuss their potential educational value. Descriptive analysis was conducted on 1,024 encounter records collected over four unique 1-week-long trips by a North American institution serving Haitian migrant workers in La Romana, Dominican Republic. The top five diagnoses seen in the clinic were gastroesophageal reflux disease (GERD), hypertension (HTN), upper respiratory infections, otitis media, and fungal skin infection. On occasion, diagnoses unique to an indigent tropical population were encountered (e.g., dehydration, malnutrition, parasites, and infections.). These findings suggest a similarity between frequently encountered diagnoses on a short-term clinical service trip in Dominican Republic and primary care presentations in developed world settings, which challenges the assumption that short-term service experiences provide exposure to rare tropical disease presentations. These findings also represent additional data that can be used to better understand the health and healthcare planning among this vulnerable population of Haitian migrant workers.

Genetic variants for long QT syndrome among infants and children from a statewide newborn hearing screening program cohort.

OBJECTIVES: Autosomal recessive long QT syndrome (LQTS), or Jervell and Lange-Nielsen syndrome (JLNS), can be associated with sensorineural hearing loss. We aimed to explore newborn hearing screening combined with electrocardiograms (ECGs) for early JLNS detection. STUDY DESIGN: In California, we conducted statewide, prospective ECG screening of children ≤ 6 years of age with unilateral or bilateral, severe or profound, sensorineural or mixed hearing loss. Families were identified through newborn hearing screening and interviewed about medical and family histories. Twelve-lead ECGs were obtained. Those with positive histories or heart rate corrected QT (QTc) intervals ≥ 450 ms had repeat ECGs. DNA sequencing of 12 LQTS genes was performed for repeat QTc intervals ≥ 450 ms. RESULTS: We screened 707 subjects by ECGs (number screened/number of responses = 91%; number of responses/number of families who were mailed invitations = 54%). Of these, 73 had repeat ECGs, and 19 underwent gene testing. No subject had homozygous or compound heterozygous LQTS mutations, as in JLNS. However, 3 individuals (with QTc intervals of 472, 457, and 456 ms, respectively) were heterozygous for variants that cause truncation or missplicing: 2 in KCNQ1 (c.1343dupC or p.Glu449Argfs*14; c.1590+1G>A or p.Glu530sp) and 1 in SCN5A (c.5872C>T or p.Arg1958*). CONCLUSIONS: In contrast to reports of JLNS in up to 4% of children with sensorineural hearing loss, we found no examples of JLNS. Because the 3 variants identified were unrelated to hearing, they likely represent the prevalence of potential LQTS mutations in the general population. Further studies are needed to define consequences of such mutations and assess the overall prevalence.

Asymptomatic maternal combined homocystinuria and methylmalonic aciduria (cblC) detected through low carnitine levels on newborn screening.

A symptom-free woman gave birth to a girl with a low carnitine level on newborn screening. The baby was unaffected, but the mother had biochemical abnormalities and mutations characteristic of the cblC defect of vitamin B(12) metabolism (late-onset form). This patient with cblC was detected through her infant's newborn screening.

Informe especial: avances en nutrición y gastroenterología

El taller de Investigación de ASPEN de 1.997 se llevó a cabo durante su reunión anual en San Francisco, el 26 de enero de 1997. El taller se centró en los avances de la investigación clínica y básica en relación con la interfase entre gastroenterología de nutrientes y luminal. Métodos: Líderes en este campo realizarón presentaciones sobre la regulación genética del desarrollo gastrointestinal; la biología molecular de la adaptación del intestino delgado; el efecto del soporte nutricional en la masa mucosa del intestino; la relación entre nutrición y motilidad gastrointestinal, absorción de nutrientes y metabolismo de substrato del tracto gastrointestinal. Resultados: Los investigadores presentaron un análisis muy amplio de cada tópico aportando información de sus propios laboratorios y de la literatura publicada. Conclusiones: Este taller puso de relieve las interacciones importantes entre nutrición y gastroenterología luminal a nivel de ciencias básicas, metabolismo/fisiología y clínica. La integración de presentaciones de diferentes disciplinas contituyó una ocación única de interacción de información e ideas para acrecentar nuestra comprensión sobre nutrición y tracto gastrointestinal.