Comparison of Recommendations for Treatment of Chronic Hepatitis C Virus Infection in Children and Adolescents: A Position Paper of the Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition.

OBJECTIVE: This position paper written by the Hepatitis Expert Team of the Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition aimed to systematically evaluate clinical practice guidelines (CPGs), medical consensus, and position papers on the use of direct-acting antivirals (DAA) to treat chronic hepatitis C virus (HCV) infection in adolescents and children in order to compare recommendations and provide the basis for developing a unified position statement. METHODS: MEDLINE, Cochrane-Library, National Guideline Clearinghouse and select websites of relevant societies/organizations were used to identify CPGs, medical consensus and position papers between 2011-2019. RESULTS: A total of 5 documents were analysed: 3 CPGs, 1 medical consensus, and 1 position paper. All publications were consistent in recommending DAA treatment for adolescents (12-17 years old) with chronic HCV infection. Similarly, all of these publications consistently recommended deferring therapy for children between 3 and 11 years of age until DAA became available as standard of care. Finally, none of the included publications recommended treating children younger than 3 years old. By contrast, there was significant discrepancy across the retrieved documents regarding specific DAA regimens and treatment strategies. CONCLUSIONS: There is strong consensus on treating all adolescents with chronic HCV infection with DAA and on delaying therapy in younger children until these agents are approved for them. Interferon-based therapies should be avoided. Specific recommendations regarding which DAA regimen to use and treatment duration varied significantly. Key stakeholders need to convene to standardize therapeutic strategies at a global level if we are to eradicate HCV in children.

Identifying term breast-fed infants at risk of significant hyperbilirubinemia.

BACKGROUND: The aim of this study was to establish a model to identify term breast-fed infants who are at risk of developing significant neonatal hyperbilirubinemia. METHODS: A prospective study was designed to investigate the effects of birth weight, mode of delivery, cephalohematoma, glucose-6-phosphate dehydrogenase (G6PD) deficiency, predischarge total serum bilirubin, variant uridine 5'diphospho-glucuronosyltransferase 1A1 (UGT1A1) gene, and hepatic solute carrier organic anion transporter 1B1 (SLCO1B1) gene on significant hyperbilirubinemia in term breast-fed neonates. Significant hyperbilirubinemia was defined as a bilirubin level exceeding the hour-specific phototherapy treatment threshold recommended by the American Academy of Pediatrics in 2004. RESULTS: Of 240 exclusively breast-fed term neonates, 26 (10.8%) had significant hyperbilirubinemia. The predischarge total serum bilirubin on the third day (odds ratio (OR) = 2.63; 95% confidence interval (CI): 1.87-3.70; P < 0.001) and the variant UGT1A1 gene at nucleotide 211 (OR = 5.00; 95% CI: 1.08-23.03; P < 0.05) were significant risk factors. The area under the receiver operating characteristic (ROC) curve of the predictive probability was 0.964 (95% CI: 0.932-0.984; P < 0.0001). CONCLUSION: Combining the total serum bilirubin on the third day and the variant UGT1A1 gene at nucleotide 211 can predict hyperbilirubinemia well in term breast-fed infants.

Oral absorbable fat-soluble vitamin formulation in pediatric patients with cholestasis.

OBJECTIVE: Fat-soluble vitamin (FSV) deficiencies are common complications in pediatric patients with chronic cholestasis. The aim of the present study was to evaluate the status of FSV deficiencies in patients under present practice and to test the effect of an oral, absorbable, fat-soluble vitamin formulation (OAFSV) in these patients. METHODS: We recruited a total of 23 pediatric patients receiving conventional FSV supplementation in a single medical center, with diagnosis of biliary atresia (10), progressive familial intrahepatic cholestasis (9), Alagille syndrome (2), and other conditions (2). Ten patients switched to OAFSV and continued for 3 months. Plasma levels of vitamins A, D, and E and an international normalized ratio (INR) for prothrombin time (PT), a surrogate marker for vitamin K deficiency, were measured. RESULTS: The proportion of patients with FSV A, D, E, and K deficiencies under conventional supplementation was 73.9%, 81.8%, 91.3%, and 20.0%, respectively. In patients with total bilirubin levels ≥3.0  mg/dL, the proportion of at least 1 FSV deficiency was 100%; and the deficiency rates of vitamin A, D, E, and K were 78.6%, 100.0%, 100.0% and 21.4%, respectively. Of the 10 patients receiving standard daily dose of OAFSV for 3 months, no adverse events or overdose effects were found. The rates of vitamin A, D, and E deficiency in the patients receiving OAFSV decreased from 80.0%, 100%, and 100%, respectively, to 70.0%, 60.0%, and 60.0% after 3 months of oral supplementation. CONCLUSIONS: High rates of FSV deficiency were found in pediatric patients with chronic cholestasis under present follow-up. OAFSV supplementation is safe and potentially effective in pediatric patients with cholestasis.

Hypocalcemia and tetany caused by vitamin D deficiency in a child with intestinal lymphangiectasia.

Primary intestinal lymphangiectasia is a rare disease of children, which is characterized by chronic diarrhea and complicated with malnutrition, including fat-soluble vitamin deficiency. We report a girl aged 4 years and 8 months who was diagnosed with the disease by endoscopic duodenal biopsy at 8 months of age. She presented initially with chronic diarrhea at 4 months of age. Generalized edema with hypoalbuminemia frequently occurred despite regular albumin supplements. Multiple vitamins initially were not supplied regularly. Episodes of tetany caused by hypocalcemia developed 4 years after the diagnosis of intestinal lymphangiectasia. Imaging study (long-bone X-ray and dual-energy X-ray absorptiometry) revealed low bone density. Complicated vitamin D deficiency [low serum 25-hydroxy vitamin D concentration (< 12.48 mmol/L, the detection limit)] and secondary hyperparathyroidism were confirmed via blood testing. Vitamin D supplementation for 3 months improved her bone density, secondary hyperparathyroidism and frequent tetany. Vitamin D status should be monitored in patients with intestinal lymphangiectasia.

Lactobacillus casei rhamnosus Lcr35 in children with chronic constipation.

BACKGROUND: The purpose of the present paper was to evaluate the efficacy of probiotics (Lactobacillus casei rhamnosus, Lcr35) for treating children with chronic constipation and to compare its effect with magnesium oxide (MgO) and placebo. METHODS: This double-blind placebo-controlled, randomized study enrolled 45 children under 10 years old with chronic constipation. They were randomly assigned to receive Lcr35 (8 x 10(8) c.f.u./day; n = 18), MgO (50 mg/kg/day; n = 18), or placebo (n = 9) orally twice daily for 4 weeks. Lactulose use (1 mL/kg per day) was allowed when no stool passage for 3 days was noted. Glycerin enema was used only when no defecation was noted for >5 days or abdominal pain was suffered due to stool impaction. Bacterial cultures of stool were performed before and after treatment to evaluate the change of intestinal flora. Comparisons of the frequency of defecation, consistency of stool and the use of lactulose or enema during the period of treatment were made among the three groups. RESULTS: The patients who received MgO or probiotics had a higher defecation frequency (P = 0.03), higher percentage of treatment success (P = 0.01), less use of glycerin enema (P = 0.04) and less hard stool (P = 0.01) than the placebo group. There was no significant difference between MgO and probiotic groups in the aforementioned comparisons. The first effect of MgO (second week) on constipation was slightly earlier than that of probiotic (second to third week). Abdominal pain occurred less frequently in the probiotic group than in both the MgO and the placebo groups (P = 0.03). There was no statistically significant difference among the three groups in the use of lactulose, episodes of fecal soiling, and change of appetite. No adverse effect was noted in probiotic and placebo groups. Only one patient in the MgO group suffered from mild diarrhea. CONCLUSION: Lcr35 was effective in treating children with chronic constipation. There is no statistically significant difference in efficacy between MgO and Lcr35, but less abdominal pain occurred when using Lcr35. Study with larger case number and longer follow up is needed in the future.