ABSTRACT
PURPOSE: This study aimed to define the genotypic and phenotypic spectrum of reversible acute liver failure (ALF) of infancy resulting from biallelic pathogenic TRMU variants and determine the role of cysteine supplementation in its treatment. METHODS: Individuals with biallelic (likely) pathogenic variants in TRMU were studied within an international retrospective collection of de-identified patient data. RESULTS: In 62 individuals, including 30 previously unreported cases, we described 47 (likely) pathogenic TRMU variants, of which 17 were novel, and 1 intragenic deletion. Of these 62 individuals, 42 were alive at a median age of 6.8 (0.6-22) years after a median follow-up of 3.6 (0.1-22) years. The most frequent finding, occurring in all but 2 individuals, was liver involvement. ALF occurred only in the first year of life and was reported in 43 of 62 individuals; 11 of whom received liver transplantation. Loss-of-function TRMU variants were associated with poor survival. Supplementation with at least 1 cysteine source, typically N-acetylcysteine, improved survival significantly. Neurodevelopmental delay was observed in 11 individuals and persisted in 4 of the survivors, but we were unable to determine whether this was a primary or a secondary consequence of TRMU deficiency. CONCLUSION: In most patients, TRMU-associated ALF was a transient, reversible disease and cysteine supplementation improved survival.
Subject(s)
Liver Failure, Acute , Liver Failure , Adolescent , Child , Child, Preschool , Humans , Infant , Young Adult , Acetylcysteine/therapeutic use , Liver Failure/drug therapy , Liver Failure/genetics , Liver Failure, Acute/drug therapy , Liver Failure, Acute/genetics , Mitochondrial Proteins/genetics , Mutation , Retrospective Studies , tRNA Methyltransferases/geneticsABSTRACT
Reactivation of hepatitis B virus (HBV) is a known complication of immune-suppressive, cytotoxic, and biological modifier therapies in patients currently infected with HBV or who have had past exposure to HBV. Nowadays, newer and emerging forms of targeted biologic therapies are available for the management of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions and solid-organ, bone marrow, or haematologic stem cell transplant but there is currently a lack of a systematic approach to the care of patients with or at risk of HBV reactivation. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) together with a working group of ESPGHAN members with clinical and research expertise in viral hepatitis developed an evidence-based position paper on reactivation of HBV infection in children identifying pertinent issues addressing the diagnosis, prevention, and treatment of this condition. Relevant clinical questions were formulated and agreed upon by all the members of the working group. Questions were answered and positions were based on evidence resulting from a systematic literature search on PubMed and Embase from their inception to July 1, 2019. A document was produced and the working group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique. A recommendation was accepted provided upon agreement by at least 75% of the working group members. This position paper provides a comprehensive update on the diagnosis, prevention and treatment of HBV reactivation in children.
Subject(s)
Antineoplastic Agents , Hepatitis B , Antineoplastic Agents/therapeutic use , Biological Therapy , Child , Hepatitis B/prevention & control , Hepatitis B virus , Humans , Immunosuppression TherapyABSTRACT
OBJECTIVES: In 2017, the European Medicines Agency and the Food and Drug Administration approved the use of the fixed-dose combination of ledipasvir/sofosbuvir and of the combination of sofosbuvir and ribavirin for treatment of adolescents (12-17 years or weighing >35âkg) with chronic hepatitis C virus (HCV) genotype 1, 4, 5, and 6 and genotype 2 and 3 infections, respectively. Although trials with direct-acting antivirals are ongoing for younger children, the only available treatment in the United States and Europe for those <12 years is still the dual therapy of pegylated interferon and ribavirin. There is currently a lack of a systematic approach to the care of these patients. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition developed an evidence-based position paper for the management of chronic HCV infection in children. METHODS: A systematic literature search and meta-analysis were performed using MEDLINE and Embase from June 1, 2007 to June 1, 2017. The approach of the Grading of Recommendations Assessment, Development and Evaluation was applied to evaluate outcomes. European Society of Pediatric Gastroenterology, Hepatology and Nutrition Committee members voted on each recommendation, using the nominal voting technique. RESULTS: The efficacy of the different direct-acting antivirals combinations tested was higher, the relapse and the treatment discontinuation rates lower when compared to pegylated interferon and ribavirin. CONCLUSIONS: This position paper addresses therapeutic management issues including goals, endpoints, indications, contraindications, and the optimal treatment regimen in children with chronic HCV infection.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Adolescent , Child , Child, Preschool , Drug Administration Schedule , Drug Combinations , Drug Therapy, Combination , Humans , InfantABSTRACT
BACKGROUND: Paediatric ulcerative colitis [UC] is more extensive than adult disease, and more often refractory to mesalamine. However, no prospective trials have evaluated mesalamine enemas for inducing remission in children. Our goal was to evaluate the ability of mesalamine enemas to induce remission in mild to moderate paediatric UC refractory to oral mesalamine. METHODS: This was an open-label arm of a previously reported randomised controlled trial of once-daily mesalamine in active paediatric UC [MUPPIT trial]. Children aged 4-18 years, with a Paediatric Ulcerative Colitis Activity Index [PUCAI] score of 10-55, were enrolled after failing at least 3 weeks of full-dose oral mesalamine. Patients treated with steroids or enemas in the previous month and those with isolated proctitis were excluded. Children received Pentasa® enemas 25 mg/kg [up to 1g] daily for 3 weeks with the previous oral dose. The primary endpoint was clinical remission by Week 3. RESULTS: A total of 38 children were enrolled (mean age 14.6 ± 2.3 years; 17/38 [45%] with extensive colitis). Clinical remission was obtained in 16 [42%] and response was obtained in 27 [71%] at Week 3. Eight children deteriorated and required steroids. There were no differences in baseline parameters between those who entered or failed to enter remission, including disease extent [43% in left-sided and 41% in extensive colitis] and disease activity [44% in mild and 41% in moderate activity]. CONCLUSION: Clinical remission can be markedly increased in children who are refractory to oral mesalamaine by adding mesalamine enemas for 3 weeks, before commencing steroids.
Subject(s)
Colitis, Ulcerative/drug therapy , Mesalamine/administration & dosage , Adolescent , Child , Child, Preschool , Enema , Female , Humans , Male , Mesalamine/therapeutic use , Prospective Studies , Remission Induction/methods , Single-Blind Method , Treatment FailureABSTRACT
OBJECTIVES: Diet assessment is essential in the care of patients with inflammatory bowel disease (IBD). We aimed to study food intake in children with IBD and evaluated the relation of dietary intake with disease activity and nutritional status in these children. METHODS: This cross-sectional study investigated 68 children and adolescents with IBD (57 Crohn disease, 11 ulcerative colitis). Evaluation included clinical, laboratory, and nutritional assessment including 3 days diet record. RESULTS: Compared with recommended daily allowance, the intake of patients with IBD was significantly poor for carbohydrates (75%, Pâ=â0.016), calcium (49%, Pâ<â0.05), magnesium (76%, Pâ<â0.05), vitamin A (72%, Pâ<â0.05), vitamin E (57%, Pâ<â0.05), and fiber (44%, Pâ<â0.05) and higher for protein (175%, Pâ<â0.05), iron (112%, Pâ<â0.05), and water-soluble vitamins (118%-189% Pâ<â0.05). Compared with the intakes of healthy children from National Nutritional Survey, the intake of IBD group was lower for calories (78%, Pâ=â0.012), carbohydrates (61% Pâ<â0.05), magnesium (67% Pâ<â0.05), vitamin C (34%, Pâ<â0.05), and fiber (54%, Pâ<â0.05) and high for B12 (141%, Pâ<â0.05). Fifty subjects ate ordinary diets, 7 of 68 children were on exclusive enteral nutrition and 11 of 68 consumed regular food with different polymeric formulas supplements. Compared with children without supplements, children on exclusive enteral nutrition and nutritional supplements (18/68) had significantly better intakes of energy (1870â±â755 vs 2267â±â432, Pâ<â0.05), carbohydrates (223â±â97 vs 292â±â99, Pâ<â0.05), and all minerals (Pâ<â0.05) and micronutrients (Pâ<â0.05). Dietary intake was not different by disease status (remission or relapse). CONCLUSIONS: In the absence of nutritional supplements, food intake is inadequate for many nutrients in many children with IBD.