Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency.

BACKGROUND AND AIMS: Mutations in ATPase phospholipid transporting 8B1 (ATP8B1) can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1. The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long-term outcome. We aimed to provide insights by using the largest genetically defined cohort of patients with FIC1 deficiency to date. APPROACH AND RESULTS: This multicenter, combined retrospective and prospective study included 130 patients with compound heterozygous or homozygous predicted pathogenic ATP8B1 variants. Patients were categorized according to the number of PPTMs (i.e., splice site, frameshift due to deletion or insertion, nonsense, duplication), FIC1-A (n = 67; no PPTMs), FIC1-B (n = 29; one PPTM), or FIC1-C (n = 34; two PPTMs). Survival analysis showed an overall native liver survival (NLS) of 44% at age 18 years. NLS was comparable among FIC1-A, FIC1-B, and FIC1-C (% NLS at age 10 years: 67%, 41%, and 59%, respectively; P = 0.12), despite FIC1-C undergoing SBD less often (% SBD at age 10 years: 65%, 57%, and 45%, respectively; P = 0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10 years, sBAs < 194 µmol/L: 49% vs. sBAs ≥ 194 µmol/L: 15%; P = 0.03). SBD decreased sBAs (230 [125-282] to 74 [11-177] µmol/L; P = 0.005). SBD (HR 0.55, 95% CI 0.28-1.03, P = 0.06) and post-SBD sBA concentrations < 65 µmol/L (P = 0.05) tended to be associated with improved NLS. CONCLUSIONS: Less than half of patients with FIC1 deficiency reach adulthood with native liver. The number of PPTMs did not associate with the natural history or prognosis of FIC1 deficiency. sBA concentrations at initial presentation and after SBD provide limited prognostic information on long-term NLS.

Non-Alcoholic Fatty Liver Disease in Children and Adolescents: Lifestyle Change - a Systematic Review and Meta-Analysis.

INTRODUCTION AND AIM: This manuscript seeks to analyze the impact of lifestyle changes on body mass index (BMI), aminotransferases and steatosis in children and adolescents with nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: A review of PubMed, BIREME, Scopus, EMBASE, Medline and Web of Science databases 2015 was performed seeking studies addressing the impact of lifestyle interventions on children and/or adolescents with NAFLD. Inclusion were manuscripts written in Portuguese, English and Spanish, as well as age less than 18 years. Two reviewers performed the data extraction independently and differences were resolved by consensus. Outcome measures were BMI, serum aminotransferase levels and the presence of hepatic steatosis. RESULTS: The literature search identified 71,012 articles. After excluding 46,397 duplicates and other clearly irrelevant studies, 89 publications were reviewed in detail. Another 55 studies were excluded at this stage. Subsequently, 18 were excluded due to lack of data and three new articles were found in the review of the references of previously identified manuscripts. Therefore, 19 studies that had evaluated 923 subjects (477 boys and 446 girls) aged 6-18 years were included in the review. In most studies, the intervention included aerobic exercise and diet. In nine studies, BMI improved significantly following the intervention. The vast majority of studies reported a benefit from the intervention on aminotransferase levels. Lifestyle changes also had a significant impact on steatosis, reducing the risk by 61%. CONCLUSIONS: Lifestyle changes lead to significant improvements in BMI, aminotransferase levels and hepatic steatosis in children and adolescents with NAFLD.

A two-dose combined vaccine against hepatitis A and hepatitis B in healthy children and adolescents compared to the corresponding monovalent vaccines.

BACKGROUND: Immunization against hepatitis A and B has been available for some time, protecting against both infections. With a view to achieving further reduction in the number of interventions and increasing convenience of the vaccinee, we investigated the reactogenicity and immunogenicity of a combined hepatitis A and B vaccine in healthy 4- to 20-year-old subjects at a 0, 6-month schedule. METHODS: Two hundred forty-eight study subjects were allocated to two study groups and received either two doses of the combined hepatitis A and B vaccine (68% of subjects) or the corresponding monovalent hepatitis A and hepatitis B vaccines (32% of subjects) concomitantly in opposite arms. Reactogenicity was assessed via diary cards after each vaccination. Serum samples were analyzed at months 1, 2, 6, and 7. RESULTS: All vaccines were well tolerated and very few symptoms were scored as severe. All but one subject seroconverted for anti-hepatitis A virus (anti-HAV) antibodies (98.6%) and 100% of subjects seroconverted for anti-hepatitis B (HBs) antibodies, with respective seroprotection rates of 98.7% for the combined vaccine group and 95.9% for the concomitant vaccine group (p >0.05), respectively. Geometric mean titers were higher in the group receiving the combined vaccine: 6,635 mIU/mL vs. 2,728 mIU/mL (p = 0.0001) for anti-HAV and 3,362 mIU/mL vs. 1,724 mIU/mL (p = 0.0205) for anti-HBs, respectively. Younger subjects had a stronger immune response compared to older subjects. CONCLUSIONS: The combined hepatitis A and B vaccine was well tolerated at this two-dose schedule. The combined vaccine had higher immunogenicity, probably explained by a adjuvant effect of the antigens. Vaccination programs requiring fewer injections will most likely have a positive impact on compliance rate and comfort of the vaccinee.