Fibrosis-Related Gene Profiling in Liver Biopsies of PiZZ α1-Antitrypsin Children with Different Clinical Courses.

PiZZ (Glu342Lys) α1-antitrypsin deficiency (AATD) is characterized by intrahepatic AAT polymerization and is a risk factor for liver disease development in children. The majority of PiZZ children are disease free, hence this mutation alone is not sufficient to cause the disease. We investigated Z-AAT polymers and the expression of fibrosis-related genes in liver tissues of PiZZ children with different clinical courses.

Population-based incidence and risk factors for cholestasis in hemolytic disease of the fetus and newborn.

Objective: To estimate the incidence of cholestasis in neonates with hemolytic disease of the fetus and newborn (HDFN) and investigate risk factors and long-term liver disease.

Study Design: A population-based cohort study of all infants born with HDFN within the Stockholm region between 2006 and 2015. The study period was the first 90 days of life, and presence of any chronic liver disease was evaluated at two years of age.

Preserved renal function during long-term follow-up in children with chronic liver disease.

Aim: We have previously found well-maintained renal function in children with new-onset chronic liver disease. In this study, we investigated their renal function during long-term follow-up of the disease.

Methods: In a study of 289 children with chronic liver disease, renal function was investigated as glomerular filtration rate (GFR) measured as clearance of inulin or iohexol.

High Rate of Cytomegalovirus Detection in Cholestatic Preterm Infants.

To evaluate the prevalence of cytomegalovirus (CMV) infection in preterm infants with cholestasis. Preterm infants (<37 weeks gestational age) with cholestasis were tested for CMV DNA using Taqman PCR in blood cells from sedimented whole blood, plasma, and urine. Infants were regarded as positive for CMV if any sample was tested positive.

DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for Alagille syndrome.

Organ function depends on tissues adopting the correct architecture. However, insights into organ architecture are currently hampered by an absence of standardized quantitative 3D analysis. We aimed to develop a robust technology to visualize, digitalize, and segment the architecture of two tubular systems in 3D: oble resin asting micro computed omography (DUCT).

Cholestasis after very preterm birth was associated with adverse neonatal outcomes but no significant long-term liver disease: A population-based study.

Aim: To describe outcome linked to neonatal cholestasis in a defined cohort of very preterm infants.

Methods: Population-based retrospective case-control study of preterm infants, gestational age <30 weeks, surviving for 28 days, in Stockholm County. Cholestasis was defined as conjugated bilirubin ≥30 μmol/L exceeding 20% of total level at least twice and graded as high if exceeding 100 μmol/L.

Research priorities for liver glycogen storage disease: An international priority setting partnership with the James Lind Alliance.

The international liver glycogen storage disease (GSD) priority setting partnership (IGSDPSP) was established to identify the top research priorities in this area. The multiphase methodology followed the principles of the James Lind Alliance (JLA) guidebook. An international scoping survey in seven languages was distributed to patients, carers, and healthcare professionals to gather uncertainties, which were consolidated into summary questions.

Well Preserved Renal Function in Children With Untreated Chronic Liver Disease.

Objectives: On the basis of studies with hepatorenal syndrome, it is widely regarded that renal function is impacted in chronic liver disease (CLD). Therefore, we investigated renal function in children with CLD.

Methods: In a retrospective study of 277 children with CLD, renal function was investigated as glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), measured as clearance of inulin and para-amino hippuric acid or clearance of iohexol.

The coming of age of a young subspecialty: paediatric hepatology.

Unlabelled: Paediatric hepatology dates from the 1970s and it is the youngest of the organ-specific subspecialties. As then there have been impressive achievements in the fields of anatomical, metabolic, immunological and neoplastic diseases, and the advent of modern molecular biology has resulted in a marked increase in exact diagnoses. Liver transplants provided enormous stimulus for the discipline.

Oral Tocofersolan Corrects or Prevents Vitamin E Deficiency in Children With Chronic Cholestasis.

Objectives: D-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic cholestasis.

Methods: Two hundred seventy-four children receiving Vedrop for vitamin E deficiency or for its prophylaxis were included from 7 European centers.

CD13 Autoantibodies Are Elevated in Sera From Mothers of Infants With Neonatal Cholestasis of Different Causes.

Objectives: Human cytomegalovirus (HCMV) infection induces production of CD13-specific autoantibodies, which may promote inflammation and tissue damage. HCMV infection has been suggested as a cause of biliary atresia (BA), but little is known of its role in other forms of neonatal cholestasis. We studied serum levels of CD13-specific autoantibodies in mothers of infants with neonatal cholestasis of different causes, including BA, and in mothers of healthy, term infants without cholestasis, as well as in healthy blood donors.

Impact of parenteral fat composition on cholestasis in preterm infants.

Objectives: Parenteral nutrition-associated liver disease (PNALD) is frequently detected in neonatal intensive care units. Parenteral lipid emulsion (PLE) content has been implicated in its pathogenesis. We aimed to study the effect on incidence and outcome of PNALD by replacing soy-based PLE with olive oil-based PLE in a population-based group of preterm infants.

Thrombin generation test in children and adolescents with chronic liver disease.

Introduction: The aim of this study was to evaluate if real-time thrombin generation assay provides additional information to assess the hemostatic balance in children with liver disease as compared to routine coagulation tests.

Patients And Methods: Sixty-three children with chronic liver disease were enrolled at our tertiary referral center for pediatric hepatology, eight whose routine coagulation tests gave abnormal results (Group A) and 55 whose test results were normal (Group B). Abnormal routine coagulation test was defined as at least one of the following: international normalized ratio≥1.

The international normalized ratio according to Owren in liver disease: interlaboratory assessment and determination of international sensitivity index.

Introduction: The international normalized ratio (INR) is used to prioritize liver disease patients for transplantation. Previous studies have shown high interlaboratory variability in Quick-based INR determinations in samples of patients with liver disease. We assessed Owren-based INR reagents for analyzing INR in patients with liver disease.

Budesonide versus prednisone with azathioprine for the treatment of autoimmune hepatitis in children and adolescents.

Objective: To compare the effect of budesonide vs prednisone therapy both in combination with azathioprine in pediatric patients with autoimmune hepatitis (AIH).

Study Design: Forty-six patients with AIH (11 males and 35 females) aged 9-17 years were enrolled in a 6-month, prospective, double-blind, randomized, active-controlled, multicenter phase IIb study evaluating budesonide (n = 19; 3 mg twice or 3 times daily) vs prednisone (n = 27; 40 mg/day tapered to 10 mg/day), both with azathioprine (1-2 mg/kg/day), followed by a further 6 months of open-label budesonide therapy. The primary efficacy endpoint was complete biochemical remission (normal serum alanine aminotransferase and aspartate aminotransferase levels) without predefined steroid-specific side effects.

Complete Deletion of a POLG1 Allele in a Patient with Alpers Syndrome.

Mutations in the gene encoding the catalytic subunit of polymerase γ (POLG1) are a major cause of human mitochondrial disease. More than 150 different point mutations in the gene have been reported to be disease causing, resulting in a large range of clinical symptoms. Depending on the mutation or combination of mutations, disease onset can occur in early infancy or late in adult life.

Bile acids and coagulation factors: paradoxical association in children with chronic liver disease.

Objective: To examine whether there is an association between bile acids and coagulation factors in children with chronic liver disease.

Methods: Forty-five patients (age 2.8 months-18.

Tacrolimus without or with the addition of conventional immunosuppressive treatment in juvenile autoimmune hepatitis.

Aim: To investigate tacrolimus (Tac)-based treatment in juvenile autoimmune hepatitis (AIH). Twenty patients (13 girls; age, 8-17 years; median, 13.25 years) with AIH were treated with two daily oral doses of Tac.

Hepatobiliary scintigraphy during cholestatic and noncholestatic periods in patients with progressive familial intrahepatic cholestasis after partial external biliary diversion.

Background: The purpose of the study was to determine the distribution of excreted bile during cholestatic periods and in remission in patients with progressive familial intrahepatic cholestasis (PFIC) after surgery with partial external biliary diversion (PEBD), using hepatobiliary scintigraphy.

Methods: Using intravenously administered technetium Tc 99m-labeled mebrofenin, the distribution of bile during periods of biochemical cholestasis and in remission was investigated in patients with PFIC operated with PEBD. Stomal bile, urine, and feces from the patients were collected during 24 hours after administration of technetium Tc 99m-labeled mebrofenin; and the fractions of remaining radioactivity in the 3 compartments and the remaining isotopic activity in the body were quantified using scintigraphy.

Off-label drug use evaluation in paediatrics--applied to ciprofloxacin when used as treatment of cholangitis.

Purpose: To evaluate drug and indication specific off-label use in paediatrics, applied to ciprofloxacin (CPFX) in cholangitis.

Methods: We collected four different sets of data for an off-label drug use evaluation. (1) Literature review from medical journals, (2) the use and safety profile from the whole Swedish paediatric population by extracting data from national registers, (3) locally performed retrospective drug chart reviews, and (4) interviews regarding paediatric patients with CPFX treated cholangitis.