Search

Background: Medical advances have dramatically improved the long-term prognosis of children and adolescents with once-fatal hepatobiliary diseases. However, there is no generally accepted optimal pathway of care for the transition from paediatric care to the adult health system., Aim: The purpose of this position paper is to propose a transition process for young people with paediatric onset hepatobiliary diseases from child-centred to adult-centred healthcare services., Methods: Seventeen ESPGHAN/EASL physicians from 13 countries (Austria, Belgium, France, Germany, Hungary, Italy, the Netherlands, Norway, Poland, Spain, Sweden, Switzerland, and United Kingdom) formulated and answered questions after examining the currently published literature on transition from childhood to adulthood. PubMed and Google Scholar were systematically searched between 1980 and January 2018. Quality of evidence was assessed by the Grading of Recommendation Assessment, Development and Evaluation (GRADE) system. Expert opinions were used to support recommendations whenever the evidence was graded weak. All authors voted on each recommendation, using the nominal voting technique., Results: We reviewed the literature regarding the optimal timing for the initiation of the transition process and the transfer of the patient to adult services, principal documents, transition multi-professional team components, main barriers, and goals of the general transition process. A transition plan based on available evidence was agreed focusing on the individual young people's readiness and on coordinated teamwork, with transition monitoring continuing until the first year of adult services.We further agreed on selected features of transitioning processes inherent to the most frequent paediatric-onset hepatobiliary diseases. The discussion highlights specific clinical issues that will probably present to adult gastrointestinal specialists and that should be considered, according to published evidence, in the long-term tracking of patients., Conclusions: Transfer of medical care of individuals with paediatric onset hepatobiliary chronic diseases to adult facilities is a complex task requiring multiple involvements of patients and both paediatric and adult care providers.

Chronic liver disease is a growing problem that has substantial effects on public health. Many paediatric liver conditions are precursors of adult chronic liver disease, cirrhosis, and hepatocellular carcinoma. Clinical management of Wilson's disease, autoimmune liver disease, and chronic biliary disorders, such as biliary atresia, which remains the most common paediatric chronic liver disease and indication for liver transplantation, is similar in children and adults. In the past 10 or so years, paediatric hepatology has expanded into neighbouring clinical areas, such as metabolic liver diseases and systemic conditions with liver involvement. We aim to describe some of these disorders, and outline their natural history and possible differences between management in adults and children to stimulate further debate on the optimal transition of care between paediatric and adult specialists., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Chronic liver diseases in children represent a rising problem with significant effects on public health. In fact, several pediatric liver diseases are precursors of adult chronic hepatopathies, cirrhosis and hepatocellular carcinoma. The prevalence of liver diseases in children is unknown. In the USA, every year, 15,000 children are hospitalized for liver diseases, but these disorders continue to be under-recognized or diagnosed late. The main reason is due to the frequent absence of symptoms in the vast majority of liver diseases, especially in the early stages. In the last few decades several advances have been made in understanding the pathogenesis of liver diseases, permitting the discovery of new therapeutic targets to treat liver diseases, thus improving the natural history of these disorders. In this article we discuss the most recent advances in the understanding of the pathogenesis, diagnosis and treatment of the most frequent pediatric liver diseases.

Liver biopsy (LB) is still the criterion standard procedure for obtaining liver tissue for histopathological examination and a valuable tool in the diagnosis, prognosis, and management of many parenchymal liver diseases. The aim of this position paper is to summarise the present practice of paediatric LB and make recommendations about its performance. Although histological evaluation of the liver is important in assessing prognosis and exploring treatment, noninvasive techniques (ie, imaging, laboratory markers) may replace use of liver histology. The indications for LB are changing as present knowledge of aetiologies, pathomechanism, and therapeutic options in paediatric liver disease is evolving. Adult and paediatric literature was reviewed to assess the existing clinical practice of LB with focus on the technique, indications, risk of complications, and contraindications in paediatrics. This position paper presents types of LB, indications, complications, contraindications, and an essential checklist for paediatric LB.

The presence of elevated aminotransferases on routine blood tests can reveal liver diseases of various severities. In children, etiologies are more numerous and complex than those usually considered in adults. Information derived from family and personal history, physical examination and basic laboratory data are necessary to reach a timely and correct diagnosis. A stepwise approach is proposed to guide the timing of more specific investigations that are often required., (Copyright © 2014. Published by Elsevier Masson SAS.)

Autoimmune liver diseases are characterized histologically by a dense mononuclear cell infiltrate in the portal tract and serologically by high levels of transaminases and immunoglobulin G (IgG) and positive autoantibodies, in the absence of a known etiology. In pediatrics, there are three liver disorders in which liver damage is likely to arise from an autoimmune attack: autoimmune hepatitis (AIH); autoimmune sclerosing cholangitis (ASC); and de novo autoimmune hepatitis after liver transplantation. The exact pathogenesis of AIH is still unknown, but it is known that unidentified environmental factors, and occasionally drugs, might trigger disease in genetically-susceptible individuals. The clinical spectrum of disease is very wide, ranging from asymptomatic individual with abnormal liver function test to fulminant liver failure. The diagnosis is based on the combination of biochemical and histological parameters, and exclusion of other liver diseases. It is a relatively rare but devastating disease, which progresses rapidly unless immunosuppressive treatment is started promptly. Standard therapy consists of a combination of corticosteroids and azathioprine, which is efficacious in 80% of patients. Alternative therapies are increasingly being explored in patients who do not respond to the standard treatment and/or have intolerable side effects. The purpose of this review was to provide an overview of the current knowledge on pediatric autoimmune liver disease.

Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount of mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Biliary atresia is a neonatal obstructive cholangiopathy characterized by a destructive, obliterative process affecting both the intrahepatic and extrahepatic ducts of the biliary tree that uniquely presents in the first months of life. The consequence of progressive inflammatory and sclerotic reaction is the development of obstructive jaundice. To determine the proinflammatory cytokine profile in children with biliary atresia, we measured circulating levels of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha and IL-8., Methods: Twelve children, five males and seven females, with biliary atresia were studied. In addition, four patients with progressive familial intrahepatic cholestasis and three with Alagille syndrome were also included. Five patients with neonatal hepatitis were studied as controls of a liver disease without portal fibrosis. Serum concentration of total and conjugated bilirubin, gamma-glutamyl transferase and glutamic-pyruvic transaminase were measured by routine methods in all patients at time of sampling for the study. The degree of fibrosis in liver biopsies was scored using the histologic activity index., Results: In our study IL-8 was detectable in 11 of 12 patients with biliary atresia with a median level of 262 pg/ml and a highly statistically significant difference (P < 0.0001) from controls. In patients with progressive familial intrahepatic cholestasis or with Alagille syndrome serum IL-8 levels were similarly elevated. In patients with neonatal hepatitis, IL-8 levels were marginally increased. Serum IL-8 levels were significantly correlated (Rs = 0.725, P < 0.0001) with the histologic activity index., Conclusions: Although further studies are needed to determine the role of IL-8 in portal inflammation, our results suggest that increased production of IL-8 may be a mechanism leading to the progressive portal inflammation and fibrosis in patients with chronic liver disease.

Background: Percutaneous biopsy of the liver is the most commonly used procedure to obtain tissue for histopathological assessment of liver disease. Although, intuitively, image-guided liver biopsy might be expected to reduce the risk of bleeding, haematoma caused by a penetrating injury of a branch of the hepatic artery or portal vein, and puncture of the gallbladder, no trial has been large enough to show reduced mortality or morbidity with US guidance, and the mechanisms by which the use of US can reduce the risk of bleeding remain speculative., Objective: To compare the mortality and morbidity of blind liver biopsy with that of US-guided liver biopsy., Materials and Methods: A retrospective review of our experience of 140 procedures over a 16-month period., Results: In the blind group, biopsy was unsuccessful in ten children (95% CL 7.3-25.4); no tissue was obtained in eight children and an inadequate sample was obtained in two. Three children (95% CL 9.2-14.7) suffered significant haemorrhage (indicated by a drop in haemoglobin of >20 g/l) with intrahepatic ( n=1) and subcapsular ( n=2) haematomas detectable by US after biopsy. An adequate sample was obtained in all children in the US-guided group. There were no complications requiring treatment in either group., Conclusions: Our results showed a significant difference in the complication rate between liver biopsy undertaken with US guidance and liver biopsy performed blind ( P=0.002).

Background:Nowadays, non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children. Our recent clinical trial demonstrated that dietary and VSL#3-based interventions may improve fatty liver by ultrasound and body mass index (BMI) after 4 months.Objectives:As in this short-term trial, as in others, it is impracticable to monitor response to therapy or treatment by liver biopsy, we aimed to identify a panel of potential non-invasive metabolic biomarkers by a urinary metabolic profiling.Methods:Urine samples from a group of 31 pediatric NAFLD patients, enrolled in a VSL#3 clinical trial, were analyzed by high-resolution proton nuclear magnetic resonance spectroscopy in combination with analysis of variance-Simultaneous Component Analysis model and multivariate data analyses. Urinary metabolic profiles were interpreted in terms of clinical patient feature, treatment and chronology pattern correlations.Results:VSL#3 treatment induced changes in NAFLD urinary metabolic phenotype mainly at level of host amino-acid metabolism (that is, valine, tyrosine, 3-amino-isobutyrate or β-aminoisobutyric acid (BAIBA)), nucleic acid degradation (pseudouridine), creatinine metabolism (methylguanidine) and secondarily at the level of gut microbial amino-acid metabolism (that is, 2-hydroxyisobutyrate from valine degradation). Furthermore, some of these metabolites correlated with clinical primary and secondary trial end points after VSL#3 treatment: tyrosine and the organic acid U4 positively with alanine aminotransferase (R=0.399, P=0.026) and BMI (R=0.36, P=0.045); BAIBA and tyrosine negatively with active glucagon-like-peptide 1 (R=−0.51, P=0.003; R=-0.41, P=0.021, respectively).Conclusions:VSL#3 treatment-dependent urinary metabotypes of NAFLD children may be considered as non-invasive effective biomarkers to evaluate the response to treatment. [ABSTRACT FROM AUTHOR]

Intrauterine growth retardation predisposes toward long-term morbidity from type 2 diabetes and cardiovascular disease. To explain this association, the concept of programming was introduced to indicate a process whereby a stimulus or insult at a critical period of development has lasting or lifelong consequences on key endocrine and metabolic pathways. Subtle changes in cell composition of tissues, induced by suboptimal conditions in utero, can influence postnatal physiological functions. There is increasing evidence, suggesting that liver may represent one of the candidate organs targeted by programming, undergoing structural, functional and epigenetic changes following exposure to an unfavorable intrauterine environment. The aim of this review is to provide insights into the molecular mechanisms underlying liver programming that contribute to increase the cardiometabolic risk in subjects with intrauterine growth restriction. [ABSTRACT FROM AUTHOR]

Abstract: Pediatric liver transplantation is the treatment of choice for end-stage liver disease of various causes. With most patients surviving long term after surgery, questions and concerns nowadays focus on morbidity and quality of life. Characterizing health-related quality of life (HRQOL) after liver transplantation provides a more complete estimate of the overall health of liver transplant candidates and recipients. HRQOL remains, however, a wide concept, with various interpretations in the literature, varying from medical assessment of physical status to considering various nonmedical aspects. Among the former aspects, concerns are commonly addressed about physical health and the psychological and/or social functioning of both transplanted children and their families. This detailed review of the most relevant papers analyzing of HRQOL after pediatric liver transplantation published between January 2006 and September 2008 includes the psychosocial aspects in children/adolescents, parents, and/or family members after liver transplantation, emphasizing limitations inherent to “measuring” and analyzing HRQOL aspects. [Copyright &y& Elsevier]

Objective: Waist circumference is widely accepted as a risk factor for cardiovascular disease and metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) is a feature of the metabolic syndrome. A contribution of metabolic syndrome, and especially of waist circumference, to liver fibrosis in children with NAFLD is strongly suspected. Design: Cross-sectional study. Setting: Department of Hepatogastroenterology and Nutrition, Paediatric Hospital "Bambino Gesù", Rome, Italy. Patients: 197 consecutive Caucasian children with NAFLD (136 males and 61 females) aged 3-19 years. Main outcome measures: Multivariable logistic regression models were used to examine the contribution of gender, age, body mass index (BMI) and metabolic syndrome components (waist circumference, high-density lipoprotein (HDL)-cholesterol, triglycerides, blood pressure and glucose) to the odds of liver fibrosis as detected by liver biopsy. Results: 92% of the children had BMI ⩾85th percentile and 84% had a waist ⩾90th percentile for gender and age. Ten per cent of the children had metabolic syndrome and 67% had liver fibrosis, mostly of low degree. At multivariable analysis, waist was the only metabolic syndrome component to be associated with liver fibrosis. This was seen both when the components of the metabolic syndrome were coded as dichotomous (odds ratio (OR) = 2.40; 95% confidence interval (Cl), 1.04 to 5.54) and continuous (OR = 2.07; 95% CI, 1.43 to 2.98 for a 5 cm increase). In the latter case, age was also associated with the outcome (OR = 0.70; 95% Cl, 0.55 to 0.89 for a 1 year increase). Conclusions: Abdominal rather than generalised obesity contributes to liver fibrosis in children with NAFLD. Waist is also the only component of the metabolic syndrome to be associated with fibrosis in these children. Therefore, the presence of abdominal obesity is an additional criterion for the selection of children and adolescents who should undergo extensive investigation, including liver biopsy. [ABSTRACT FROM AUTHOR]

Objective:Our aim was to estimate prevalence of metabolic syndrome (MS), obesity and comorbidities in a cohort of 120 children (3–18 years) with biopsy-proven non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) and to evaluate correlations between clinical or biochemical variables and liver histology.Research methods and procedures:MS was diagnosed according to the adapted National Cholesterol Education Program criteria. Homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI); and ISI composite, insulin secretion (insulin response at 30 min after a glucose load; HOMA-β cell; insulinogenic index) were all estimated. BMI z-score and total body fat (dual-energy X-ray absorptiometry) were evaluated as indexes of obesity.Results:MS was diagnosed in 66% of children. About 92% had weight above the 85th percentile, of which 42% were obese with weight above 97th percentile. Prevalence of hypertriglyceridaemia was 63%, low HDL cholesterol 45%, hypertension 40% and impaired glucose tolerance 10%. Levels of aminotransferases were higher as the number of comorbidities increased, the highest values being found in subjects with MS (P0.05). Prevalence of a grade of steatosis 2 (P=0.05) and fibrosis (P0.01) was higher in subjects with MS. Histology was associated significantly with higher values of a number of clinical and biochemical parameters (steatosis 2 with BMI z-score (P=0.04), fasting insulin (P=0.02), HOMA-IR (P=0.03), β-cell secretion (P=0.04); necroinflammation with BMI z-score (P=0.007), glucose (P0.0001), cholesterol (P0.04) and white blood cells (P=0.025); fibrosis with body weight (P=0.05), BMI z-score (P=0.03), cholesterol (P=0.05), triglycerides (P=0.05), fasting insulin (P0.0001) and mean values of the hormone at the OGTT (P=0.03), HOMA-IR (P0.0001)).Conclusion:Presence of MS or clinical and biochemical variables associated with the syndrome seems to be strictly related to histological features of NASH in paediatric fatty liver disease. Thus, routinely liver biopsy should be encouraged in these children.International Journal of Obesity (2008) 32, 381–387; doi:10.1038/sj.ijo.0803711; published online 18 December 2007 [ABSTRACT FROM AUTHOR]

Background Few data are available on the effect of antioxidants in paediatric non-alcoholic fatty liver disease (NAFLD). Aim To compare the effect of a nutritional programme alone or combined with alpha-tocopherol and ascorbic acid on alanine aminotransferase (ALT) levels, and insulin resistance (IR) in biopsy-proven NAFLD children. Methods In a 12-month double-blind placebo study, 90 patients were prescribed a balanced calorie diet (25–30 cal/kg/d), physical exercise, and placebo (group A) or alpha-tocopherol 600 IU/day plus ascorbic acid 500 mg/day (group B). IR was estimated by the homeostasis model assessment (HOMA-IR). Results At month 12, ALT (32.67 ± 8.09 vs. 32.18 ± 11.39 IU/L; P = NS), HOMA-IR (1.52 ± 0.66 vs. 1.84 ± 0.95 IU/L; P = NS), and weight loss (32% vs. 35% of excessive body weight; P = NS) did not differ between the two arms. Among subjects who lost ≥20% of their excessive weight, ALT and body weight percentage changes were significantly related ( ro = 0.260; P = 0.03). In subjects, who lost more than 1.0 kg, HOMA-IR significantly decreased (2.20 ± 0.21 to 1.57 ± 0.13 in group A ( P ≤ 0.01; −8%); 2.91 ± 0.24 to 1.88 ± 0.16 in group B (−32%; P ≤ 0.0001)). ALT decreased by 36% (59.13 ± 4.11 vs. 30.27 ± 1.46 IU/L; P ≤ 0.001), and 42% (68.19 ± 5.68 vs. 31.92 ± 1.92 IU/L; P ≤ 0.0001). In a multivariate analysis, fasting insulin changes in group A ( P = 0.012; F = 7.150). Conclusions Diet and physical exercise in NAFLD children seem to lead to a significant improvement of liver function and glucose metabolism beyond any antioxidant therapy. [ABSTRACT FROM AUTHOR]