Treatment of hepatitis C in children with direct-acting antiviral drugs.

The primary purpose of treating chronic hepatitis C (HCV) is to prevent the development of liver fibrosis, cirrhosis, and cancer. In the last decade, direct-acting antiviral medicine (DAA) has been approved to treat children with HCV. This treatment has a higher efficacy, shorter duration, and milder side effects than the previously approved treatment. In this review, it is recommended to track down children who might be infected with HCV to enhance early treatment to prevent transmission of the virus and the possible complications.

Towards a model of biliary atresia - Pilot feasibility study in newborn piglets.

Biliary atresia (BA) is a rare congenital liver disease with unknown etiology, and it is the most common indication for liver transplantation in children. As BA infants suffer from intestinal malabsorption and neurodevelopmental deficits, it is necessary to identify optimal medical and nutritional strategies using appropriate neonatal animal models. We aim to determine the feasibility of using newborn piglets with surgically induced cholestasis (bile duct ligation (BDL)) to mimic clinical features of BA. Six piglets were subjected to abdominal surgery on day 4 after birth. The bile ducts were ligated, and the piglet were followed for up to 12 days. On day 12 the piglets were subjected to a hepatobiliary scintigraphy using the tracer radiolabeled Technetium(99m-tc)-mebrofenin, and blood samples were collected for biochemical profiling. Of the six piglets, hepatobiliary scintigraphy verified that two piglets (BDL) had no excretion of bile into the duodenum, i.e. full cholestasis with a hepatic extraction fraction of 84-87% and clearance time of 230-318 min. One piglet (SHAM) had bile excretion to the duodenum. In accordance with this, the BDL piglets had steatorrhea, and increased levels of bilirubin and gammaglutamyl transferase (GGT). The last three piglets were euthanized due to bile leakage or poor growth. Surgically induced cholestasis in young piglets, may offer an animal model that displays clinical characteristics of biliary atresia, including malabsorption, hyperbilirubinaemia, increased GGT and reduced hepatic excretory function. Following refinement, this animal model may be used to optimize feeding strategies to secure optimal nutrition and neurodevelopment for neonatal cholestasis/BA patients.

Cholestasis alters brain lipid and bile acid composition and compromises motor function in neonatal piglets.

Infants with neonatal cholestasis are prone to neurodevelopmental deficits, however, the underlying pathogenesis is unclear. Lipid malabsorption and accumulation of potentially neurotoxic molecules in the blood such as bile acids are important yet relatively unexplored pathways. Here, we developed a translational piglet model to understand how the molecular bile acid and lipid composition of the brain is affected by this disease and relates to motor function. Piglets (8-days old) had bile duct ligation or sham surgery and were fed a formula diet for 3 weeks. Alongside sensory-motor deficits observed in bile duct-ligated animals, we found a shift toward a more hydrophilic and conjugated bile acid profile in the brain. Additionally, comprehensive lipidomics of the cerebellum revealed a decrease in total lipids including phosphatidylinositols and phosphatidylserines and increases in lysophospholipid species. This was paralleled by elevated cerebellar expression of genes related to inflammation and tissue damage albeit without significant impact on the brain transcriptome. This study offers new insights into the developing brain's molecular response to neonatal cholestasis indicating that bile acids and lipids may contribute in mediating motor deficits.

Assessment of Regression Models for Adjustment of Iron Status Biomarkers for Inflammation in Children with Moderate Acute Malnutrition in Burkina Faso.

BACKGROUND: Biomarkers of iron status are affected by inflammation. In order to interpret them in individuals with inflammation, the use of correction factors (CFs) has been proposed. OBJECTIVE: The objective of this study was to investigate the use of regression models as an alternative to the CF approach. METHODS: Morbidity data were collected during clinical examinations with morbidity recalls in a cross-sectional study in children aged 6-23 mo with moderate acute malnutrition. C-reactive protein (CRP), α1-acid glycoprotein (AGP), serum ferritin (SF), and soluble transferrin receptor (sTfR) were measured in serum. Generalized additive, quadratic, and linear models were used to model the relation between SF and sTfR as outcomes and CRP and AGP as categorical variables (model 1; equivalent to the CF approach), CRP and AGP as continuous variables (model 2), or CRP and AGP as continuous variables and morbidity covariates (model 3) as predictors. The predictive performance of the models was compared with the use of 10-fold crossvalidation and quantified with the use of root mean square errors (RMSEs). SF and sTfR were adjusted with the use of regression coefficients from linear models. RESULTS: Crossvalidation revealed no advantage to using generalized additive or quadratic models over linear models in terms of the RMSE. Linear model 3 performed better than models 2 and 1. Furthermore, we found no difference in CFs for adjusting SF and those from a previous meta-analysis. Adjustment of SF and sTfR with the use of the best-performing model led to a 17% point increase and <1% point decrease, respectively, in estimated prevalence of iron deficiency. CONCLUSION: Regression analysis is an alternative to adjust SF and may be preferable in research settings, because it can take morbidity and severity of inflammation into account. In clinical settings, the CF approach may be more practical. There is no benefit from adjusting sTfR. This trial was registered at www.controlled-trials.com as ISRCTN42569496.

[Hepatitis C infection in children].

Chronic hepatitis C (HCV) infection has a prevalence of 2-3% worldwide. The vertical transmission rate is approximately 5%. There is no evidence to recommend abstinence from breastfeeding or elective C-section to prevent transmission. In children, the natural history of HCV infection is typically benign, but liver cirrhosis and hepatocellulary carcinoma are later complications. Children with HCV infection may benefit from early treatment with pegylated interferon and ribavirin with duration depending on genotype. Overall, response to antiviral treatment of HCV infected children is comparable to results in adults.

[Hepatitis B infection in children].

Chronic hepatitis B (HBV) infection is seen in 400 million persons worldwide. HBV is transmitted vertically or horizontally by infected blood and body fluids. An effective vaccine exists. Most children develop a chronic HBV infection if infected early in life. They are often in an immune-tolerant phase with no indication for antiviral treatment. Antiviral treatment with interferon or a nucleotide analogue is a possibility if the HBV infected child develops into a phase of immune activation. HBV infection can lead to liver cirrhosis and hepatocellular carcinoma.

[Elevated alanine aminotransferase in a four-year-old as an early sign of autoimmune hepatitis].

A four-year-old girl was admitted to a paediatric clinic with a palpable lymph node and elevated alanine aminotransferase (ALT) and weak positive smooth muscle cell antibodies (SMA). Liver biopsy was never done and three months later she was referred with persistent ALT elevation. Eleven years later a dermatologist recognized spider naevi. Autoimmune hepatitis was confirmed by elevation of ALT, immunoglobulin G and positive SMA and a liver biopsy showed cirrhosis and chronic hepatitis. Children with elevated ALT at repeated measurements should be thoroughly examined if no obvious reason is present.