Liver Disease In Childhood Research Articles

Reduced peroxisome proliferator-activated receptor-α and bile acid nuclear receptor NR1H4/FXR may affect the hepatic immune microenvironment of biliary atresia.

BackgroundBiliary atresia (BA) is a childhood liver disease characterized by fibrous obstruction and obstruction of the extrahepatic biliary system and is one of the most common and serious biliary disorders in infants. Significant inflammation and fibrosis of the liver and biliary tract are the most prominent features, regardless of the initial damage to the BA. Abnormalities in innate or adaptive immunity have been found in human patients and mouse models of BA. We previously reported that children with BA had abnormal lipid metabolism, including free serum carnitine.ObjectiveTo study gene and protein expression levels of the hepatic peroxisome proliferator-activated receptor-α (PPARα) signaling pathway and farnesoid X receptor (FXR) in BA and BA fibrosis, and assess their clinical values.MethodsLow expression of PPARα and NR1H4 (FXR) in BA were validated in the Gene Expression Omnibus database. Functional differences were determined by gene set enrichment analysis based on of PPARα and NR1H4 expression. BA patients from GSE46960 were divided into two clusters by using consensus clustering according to PPARα, NR1H4, and SMAD3 expression levels, and immunoinfiltration analysis was performed. Finally, 58 cases treated in our hospital were used for experimental verification. (IHC: 10 Biliary atresia, 10 choledochal cysts; PCR: 10 Biliary atresia, 14 choledochal cysts; WB: 10 Biliary atresia, 4 choledochal cysts).ResultsBioinformatics analysis showed that the expression of PPARα, CYP7A1 and NR1H4 (FXR) in the biliary atresia group was significantly lower than in the control group. More BA-specific pathways, including TGFβ signaling pathway, P53 signaling pathway, PI3K-AKT-mTOR signaling pathway, etc., are enriched in BA patients with low PPARα and NR1H4 expression. In addition, low NR1H4 expression is abundant in inflammatory responses, IL6/STAT3 signaling pathways, early estrogen responses, IL2 STAT5 signaling pathways, and TGFβ signaling pathways. The TGFβ signaling pathway was significant in both groups. According to the expression of PPARα, NR1H4 and SMAD3, a key node in TGFβ pathway, BA patients were divided into two clusters using consensus clustering. In cluster 2, SMAD3 expression was high, and PPARα and NR1H4 expression were low. In contrast to cluster 1, immune cell infiltration was higher in cluster 2, which was confirmed by immunohistochemistry. The mRNA and protein levels of PPARα and NR1H4 in BA patients were lower than in the control group by immunohistochemistry, Western blot analysis and real-time PCR.ConclusionsThe downregulation of PPARα and NR1H4 (FXR) signaling pathway may be closely related to biliary atresia.

Rare Inherited Cholestatic Disorders and Molecular Links to Hepatocarcinogenesis

Hepatocellular carcinoma (HCC) is the most common primary liver cancer affecting adults and the second most common primary liver cancer affecting children. Recent years have seen a significant increase in our understanding of the molecular changes associated with HCC. However, HCC is a complex disease, and its molecular pathogenesis, which likely varies by aetiology, remains to be fully elucidated. Interestingly, some inherited cholestatic disorders that manifest in childhood are associated with early HCC development. This review will thus explore how three genes that are associated with liver disease in childhood (ABCB11, TJP2 and VPS33B) might play a role in the initiation and progression of HCC. Specifically, chronic bile-induced damage (caused by ABCB11 changes), disruption of intercellular junction formation (caused by TJP2 changes) and loss of normal apical–basal cell polarity (caused by VPS33B changes) will be discussed as possible mechanisms for HCC development.

Intensive care, autoethnography and solidarity

This article begins by providing a personal narrative of the intensive nature of the care between myself and my mother in the context of living through childhood liver disease, transplantation and cancer, often in hospital far from home. Psychosocial studies is argued to offer reflexive ways of working to process complexity and trauma, particularly autoethnography. The strength of working with an educator who has a relational approach to teaching, demonstrating transparency in approaches to writing and learning and sharing rich personal narratives, is explored. Crociani-Windland’s approach to practising an intimate pedagogy is found to be personally transformational and echoes through my current practice as an early-career academic.

The Role of Macronutrients in the Pathogenesis, Prevention and Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD) in the Paediatric Population-A Review.

Paediatric non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in childhood. Obesity is the main risk factor. Nutrition and lifestyle are the key elements in preventing and treating NAFLD in the absence of approved drug therapy. Whilst recommendations and studies on macronutrients (carbohydrates, fat and protein) in adult NAFLD exist, the discussion of this topic in paediatric NAFLD remains contradictory. The purpose of this review is to provide state-of-the-art knowledge on the role of macronutrients in paediatric NAFLD regarding quality and quantity. PubMed was searched and original studies and review articles were included in this review. Fructose, sucrose, saturated fatty acids, trans-fatty acids and ω-6-fatty-acids are strongly associated with paediatric NAFLD. High consumption of fibre, diets with a low glycaemic index, mono-unsaturated-fatty-acids and ω-3-fatty-acids reduce the risk of childhood-onset NAFLD. Data regarding the role of dietary protein in NAFLD are contradictory. No single diet is superior in treating paediatric NAFLD, although the composition of macronutrients in the Mediterranean Diet appears beneficial. Moreover, the optimal proportions of total macronutrients in the diet of paediatric NAFLD patients are unknown. Maintaining a eucaloric diet and avoiding saturated fatty acids, simple sugars (mainly fructose) and a high-caloric Western Diet are supported by literature.

Diagnosis and treatment of biliary atresia in children

Abstract. There are relatively few severe liver diseases in childhood. Biliary atresia is one of the most difficult. Early diagnosis of this disease is the basis of the subsequent treatment algorithm. In this article, we want to present the main criteria for diagnosing biliary tract pathology in newborns and young children, as well as draw the attention of pediatricians and neonatologists to the difficulties that arise in their diagnosis. Despite the rarity of these diseases, biliary atresia, as well as other rare liver diseases, should always be considered in the diagnosis of longterm hyperbilirubinemia. Due to early diagnosis and subsequent Kasai operation, the possibility of liver transplantation, in the last two decades, there has been significant progress in the treatment of children with biliary atresia.

Early life programming of nonalcoholic fatty liver disease in children

BackgroundResearch is beginning to implicate early life characteristics in the development of pediatric nonalcoholic fatty liver disease, however the relationship with perinatal characteristics is poorly understood. AimsWe evaluated the association between perinatal characteristics and nonalcoholic fatty liver disease in childhood. Study designNested case-control study. Subjects5104 children born in Quebec, Canada between 2006 and 2019. Exposures included maternal diabetes, obesity, prematurity, and other birth complications. Outcome measuresThe outcome was nonalcoholic fatty liver disease diagnosed in hospital before 14 years of age. We calculated adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between birth characteristics and nonalcoholic fatty liver disease. ResultsA total of 104 children with nonalcoholic fatty liver disease were included. Gestational diabetes (OR 2.17, 95% CI 1.15–4.10), preexisting diabetes (OR 5.75, 95% CI 2.67–12.4), and maternal obesity (OR 3.06, 95% CI 1.71–5.45) were associated with childhood nonalcoholic fatty liver disease. Prematurity (OR 1.93, 95% CI 1.06–3.54) and neonatal intensive care unit admission (OR 2.18, 95% CI 1.10–4.33) were also associated with nonalcoholic fatty liver disease. However, there was no association with low birthweight, small-for-gestational age birth, and macrosomia. ConclusionsMaternal metabolic disorders and prematurity may initiate processes early in life that lead to the development of nonalcoholic fatty liver disease in childhood.

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

AimWe 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.MethodsIn 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. Yearly change in GFR was calculated based on a linear mixed model. The data were analysed with regard to different subgroups of liver disease and with regard to the outcome.ResultsThe initially well‐preserved renal function remained so in most patients during the observation period, even in children with progressive liver disease leading to decompensation. The greatest fall in GFR occurred in patients with initial hyperfiltration. Cholestasis seemed to have a nephroprotective effect.ConclusionChronic liver disease in childhood seems to have less impact on renal function than believed earlier, at least as long as the liver function remains compensated. Regular renal check‐ups remain an essential tool for optimal patient care. Hyperfiltration seems to predict decline in renal function. Otherwise no further reliable prognostic markers were found in patients whose liver disease was not decompensated.

Chelation therapy in liver diseases of childhood: Current status and response.

Chelation is the mainstay of therapy in certain pediatric liver diseases. Copper and iron related disorders require chelation. Wilson’s disease (WD), one of the common causes of cirrhosis in children is treated primarily with copper chelating agents like D-penicillamine and trientine. D-Penicillamine though widely used due its high efficacy in hepatic WD is fraught with frequent adverse effects resulting discontinuation. Trientine, an alternative drug has comparable efficacy in hepatic WD but has lower frequency of adverse effects. The role of ammonium tetra-thiomolybdate is presently experimental in hepatic WD. Indian childhood cirrhosis is related to excessive copper ingestion, rarely seen in present era. D-Penicillamine is effective in the early part of this disease with reversal of clinical status. Iron chelators are commonly used in secondary hemochromatosis of liver in hemolytic anemias. There are strict chelation protocols during bone marrow transplant. The role of iron chelation in neonatal hemochromatosis is presently not in vogue due to its poor efficacy and availability of other modalities of therapy. Hereditary hemochromatosis is rare in children and the use of iron chelators in this condition is limited.

Evaluation of metabolic factors affecting the presence of hepatosteatosis and the effect of insulin like growth factor-1 level in overweight and obese children

Although previous studies related to non-alcoholic fatty liver disease (NAFLD) in childhood were predominantly ALT and uric acid level, the number of studies that have been handled in terms of insulin like growth factor-1 (IGF-1) level or IGF-1 standard deviation score (SDS) is limited. In this study, all factors that may affect NAFLD, including IGF-1 level and IGF-1 SDS, were evaluated in two groups of children who were not statistically different from each other in terms of age, gender, weight, height, body mass index and puberty. This study was a cross sectional study. 36 children with evidence of fatty liver disease on ultrasound imaging and 38 children without it were included in the study. Anthropometric data, laboratory measurements and radiological results of all participants were evaluated. All factors that could affect NAFLD were evaluated by binary logistic regression analysis. Weight, weight SDS, body mass index (BMI) SDS, homeostasis model assessment of insulin resistance (HOMA-IR), AST, ALT, GGT, uric acid, triglyceride, HDLcholesterol, IGF-1, IGF-1 SDS were evaluated in this model to predict NAFLD. In the statistical model, the percentage of predicting those with NAFLD, that is, the sensitivity, was 88.9%, while the detection rate of those without NAFLD, that is, the specificity, was 94.7%. IGF-1 level was found to be significantly lower in the group with NAFLD (p: 0.04), but there was no significant difference between the groups in terms of IGF-1 SDS (p: 0.10). There are conflicting results in studies examining the relationship between IGF-1 SDS and NAFLD. This may be due to ethnicity, regional differences, kit-specific laboratory reference ranges, or method of measurement. Laboratory measurements including appropriate parameters with a detailed physical examination can be used to predict the presence of NAFLD without the need for radiological examination.

Direct Bilirubin Detection Using Surface-Enhanced Raman Spectroscopy

Biliary atresia is the most common cause of childhood liver disease and is the main cause of liver replacement. The use of an effective early screening technique can efficiently improve the therapeutic effect on children with biliary atresia, especially those in the remote rural areas. This study introduces a novel method for detecting direct bilirubin by Raman spectroscopy using composite surface-enhanced Raman spectroscopy (SERS) chips. These chips were created by spreading silver nanowires on the nanostructure surface of an anodic aluminum oxide substrate. Experimental results demonstrated that the detection limit of direct bilirubin concentration vastly improved far below the disease criteria of bilirubin in adults and infants. Meanwhile, using only <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$10~\mu \text{L}$ </tex-math></inline-formula> of direct bilirubin, a wide detection range from 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−7</sup> to 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−4</sup> M was obtained, covering the clinic reference range with R <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> of 0.98336 at the peak value of 1.616 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−1</sup> . Furthermore, the results revealed that the proposed composite SERS substrates possessed good statistical relative standard deviation and reproducibility (N = 3) of 4.6% and 2.2%, respectively. Thus, the composite SERS chip combined with the Raman spectroscopy approach can be integrated with portable Raman spectrometer for the effective clinical detection of direct bilirubin.

High Mobility Group Box 1 Release by Cholangiocytes Governs Biliary Atresia Pathogenesis and Correlates With Increases in Afflicted Infants.

Background and AimsBiliary atresia (BA) is a devastating cholangiopathy of infancy. Upon diagnosis, surgical reconstruction by Kasai hepatoportoenterostomy (HPE) restores biliary drainage in a subset of patients, but most patients develop fibrosis and progress to end‐stage liver disease requiring liver transplantation for survival. In the murine model of BA, rhesus rotavirus (RRV) infection of newborn pups results in a cholangiopathy paralleling that of human BA. High‐mobility group box 1 (HMGB1) is an important member of the danger‐associated molecular patterns capable of mediating inflammation during infection‐associated responses. In this study, we investigated the role of HMGB1 in BA pathogenesis.Approach and ResultsIn cholangiocytes, RRV induced the expression and release of HMGB1 through the p38 mitogen‐activated protein kinase signaling pathway, and inhibition of p38 blocked HMGB1 release. Treatment of cholangiocytes with ethyl pyruvate suppressed the release of HMGB1. Administration of glycyrrhizin in vivo decreased symptoms and increased survival in the murine model of BA. HMGB1 levels were measured in serum obtained from infants with BA enrolled in the PROBE and START studies conducted by the Childhood Liver Disease Research Network. High HMGB1 levels were found in a subset of patients at the time of HPE. These patients had higher bilirubin levels 3 months post‐HPE and a lower survival of their native liver at 2 years.ConclusionsThese results suggest that HMGB1 plays a role in virus induced BA pathogenesis and could be a target for therapeutic interventions in a subset of patients with BA and high HMGB1.

Surveillance of Fontan Associated Liver Disease in Childhood and Adolescence

Fontan associated liver disease (FALD) has been recognized as a potentially serious sequela of the Fontan circulation. Prevalence of FALD among different age groups and risk factors for advanced changes were assessed. FALD screening included abdominal ultrasound and laboratory tests. A "liver disease score (LDS)" incorporating items from ultrasound and blood testing was calculated to grade FALD severity (5 items each, maximum score 10 points). 240 patients (male: n = 139, female: n = 101, systemic right ventricle: n = 160) underwent FALD screening 10 (IQR 7-15) years after Fontan surgery. Ultrasound was abnormal in 184 (76.6%) patients (surface nodularity / blunted liver edge: n = 133, 55.4%; heterogeneous parenchyma: n = 93, 38.8%; splenomegaly: n = 68, 28.3%; ascites: n = 23, 9.6%). At least one abnormal laboratory test was detected in 218 (90.8%) patients. Gamma-glutamyl-transpeptidase was elevated in the majority of patients (n = 206, 85.8%). Median LDS was 3 (2-4). Scores ≥5 were observed in 32 (13.3%) patients. Longer follow-up (15 (11-20) vs 9 (6-14) years, P <0.001), higher central venous (13 (11-15) vs 10 (9-12) mmHg, P <0.001) and end-diastolic pressure (8 (5-10) vs 6 (5-7) mmHg, P = 0.001), impaired ventricular function and absence of sinus rhythm were associated with LDS ≥5. Longer follow-up (OR 1.2 (1.1-1.3), P <0.001) and higher central venous pressure (OR 1.6 (1.3-2.1), p < 0.001) were the only independent predictors of advanced FALD. Abdominal ultrasound and laboratory abnormalities suggestive of FALD are common during routine follow-up already in childhood and adolescence irrespective of ventricular morphology. More advanced findings are associated with longer follow-up and higher central venous pressure.

Biological basis of child health 9: development of the liver and clinical features of childhood liver disease.

This article is the ninth in a series on the biological basis of child health and follows on from the previous article, which discussed the gastrointestinal system. The liver is the largest solid organ in the body and has more than 500 functions. These functions include: producing bile, which serves as a vehicle for waste products and as an aid for the digestion of dietary fat; synthesising most coagulation factors, needed in the clotting cascade; and transforming glycogen into glucose for use as energy in cell metabolism. While most liver conditions seen in children are rare, it is important that children's nurses can identify the clinical features of childhood liver disease. This article provides an overview of the embryological development of the liver, its anatomy and functions, liver function tests in children, and the clinical features and pathophysiology of childhood liver disease.

Blind liver biopsy: a 17-year experience

Objectives: Liver biopsy is the gold standard for assessing liver inflammation, necrosis and fibrosis. The aim of the study is to evaluate clinical indications and histopathological results of percutaneus liver biopsy. Materials and methods: A total of 516 children who underwent blind liver biopsy were evaluated retrospectively. Results: Blind liver biopsy was performed for chronic active hepatitis B in 50% of the cases (n=260), neonatal cholestasis in 14% (n=68), autoimmune hepatitis in 7.7% (n=40), Wilson disease in 7.3% (n=38), isolated elevation of the liver enzymes in 5% (n=26), chronic active hepatitis C in 4.2% (n=22), metabolic disease in 3.4% (n=17), malignancies in 2.2% (n=11) and the others in 3.4% (n=17). Major complications were observed in 0.19% of the cases (n=1) and minor complications such as pain at the biopsy site in 13.5% of the cases (n=70), hypotension and tachycardia in 1.9% (n=10). Conclusions: Blind liver biopsy is a safe method in diagnosing liver diseases in childhood.

Non-Alcoholic Fatty Liver Disease (NAFLD) in overweight and obese children and adolescents

Over the last decades overweight, obesity and non-alcoholic fatty liver disease (NAFLD) in childhood and adolescence increased. NAFLD is strongly associated with insulin resistance, hypertension, dyslipidemia and other pro-atherogenic conditions.

Non-alcoholic fatty liver disease and metabolic syndrome in childhood

There is ample evidence that insulin resistance, hyperinsulinemia, and obesity are at the heart of the development of non-alcoholic fatty liver disease (NAFLD). The disease is now considered as the hepatic component of metabolic syndrome (MS).64 children with NAFLD were assessed for metabolic syndrome stigma. An analysis was also made on the state of the problem according to the literature on the general links of the pathogenesis of these conditions, methods of diagnosis and treatment of NAFLD.All components of MS are observed with different frequencies in patients with NAFD. This disease, together with type 2 diabetes mellitus, becomes very common diseases in childhood. The incidence of NAFLD in children is constantly growing, it has begun to occur in infants, an outcome in cirrhosis of the liver is possible within childhood, although the prognosis for NAFLD remains definitely uncertain. Weight loss with a low glycemic index diet, regular exercise, and other lifestyle changes are the mainstay of NAFLD treatment, but not yet very effective for various reasons. In these conditions, it is necessary to increase the role of primary prevention of MS and NAFLD.

Long-term results of pediatric liver transplantation for autoimmune liver disease

BackgroundAutoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) are rare indications for liver transplantation (LT) in children. The aim of the present retrospective multicenter study was to evaluate long-term outcome after LT for autoimmune liver disease in childhood. MethodsRetrospective data from 30 children who underwent a first LT from 1988 to 2018 were collected. ResultsThe study population consisted of 18 girls and 12 boys, transplanted for AIH type 1 (n=14), AIH type 2 (n=7) or PSC (n=9). Mean age at LT was 11.8±5.2 years. The main indications for LT were acute (36.7%) or chronic end-stage liver failure (63.3%). Graft rejection occurred in 19 patients (63.3%); 6 pts required retransplantation for chronic rejection. Recurrence of initial disease was observed in 6 patients (20.0%), all of them with type 1 AIH, after a median time of 42 months, requiring retransplantation in 2 cases. Overall patient survival rates were 96.4%, 84.6%, 74.8%, 68.0%, 68.0%, 68.0% and 68.0% at 1, 5, 10, 15, 20, 25 and 30 years, respectively. Age at LT<1year (p<0.0001), LT for fulminant failure (p=0.023) and LT for type 2 AIH (p=0.049) were significant predictive factors of death. ConclusionLong-term outcome after LT for pediatric autoimmune liver disease is impaired in patients with AIH because of consistent complications such as rejection and disease recurrence.

Modeling Outcomes in Children With Biliary Atresia With Native Liver After 2 Years of Age.

Approximately 50% of infants with biliary atresia (BA) undergoing Kasai portoenterostomy show survival with native liver (SNL) at age 2 years. Predictors of disease progression after age 2 years are unknown, despite estimates of 20%‐30% undergoing liver transplant (LT) between age 2 and 18 years. We sought to address this knowledge gap by developing prognostic models in participants of the multicenter prospective National Institutes of Health‐supported Childhood Liver Disease Research Network. We extracted 14 clinical and biochemical variables at age 2 years to develop two models for future outcomes: 1) LT or death (LTD) and 2) first sentinel event (SE), either new onset ascites, hepatopulmonary syndrome (HPS), or gastrointestinal (GI) bleed. A total of 240 participants, enrolled between 2004 and 2017, were followed until a median age of 5.1 years (range, 2.0‐13.3 years). Of these participants, 38 underwent LT (n = 37) or death (n = 1); cumulative incidence, 23.7% (95% confidence interval [CI], 16.2%‐32.0%). Twenty‐seven experienced either new‐onset ascites (n = 13), HPS (n = 1), or GI bleed (n = 14). One participant had ascites and GI bleed concurrently; cumulative incidence, 21.5% (95% CI, 14.2%‐29.8%) by age 10 years. The Cox proportional hazard model predicted risk of LTD, using total bilirubin, albumin, platelet count, and history of either ascites or cholangitis (BA LTD model), with a C‐index of 0.88 (range, 0.86‐0.89). A cause‐specific hazard competing risk model predicted SE using platelet count and gamma glutamyltransferase levels (BA SE model) with a C‐index of 0.81 (range, 0.80‐0.84). Internal model validity was assessed using Harrell’s C‐index with cross‐validation. Conclusion: Stratification using these models identified risk of poor outcomes in patients with BA SNL after age 2 years. The models may identify those who would benefit from enhanced clinical surveillance and prioritization in clinical trials.

Nonfasted Liver Stiffness Correlates with Liver Disease Parameters and Portal Hypertension in Pediatric Cholestatic Liver Disease.

Elastographic measurement of liver stiffness is of growing importance in the assessment of liver disease. Pediatric experiences with this technique are primarily single center and limited in scope. The Childhood Liver Disease Research Network provided a unique opportunity to assess elastography in a well‐characterized multi‐institutional cohort. Children with biliary atresia (BA), alpha‐1 antitrypsin deficiency (A1ATD), or Alagille syndrome (ALGS) followed in a prospective longitudinal network study were eligible for enrollment in a prospective investigation of transient elastography (FibroScan). Studies were performed in participants who were nonfasted and nonsedated. Liver stiffness measurements (LSMs) were correlated with standard clinical and biochemical parameters of liver disease along with a research definition of clinically evident portal hypertension (CEPH) graded as absent, possible, or definite. Between November 2016 and August 2019, 550 participants with a mean age of 8.8 years were enrolled, 458 of whom had valid LSMs (BA, n = 254; A1ATD, n = 104; ALGS, n = 100). Invalid scans were more common in participants <2 years old. There was a positive correlation between LSM and total bilirubin, international normalized ratio (INR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma‐glutamyl transpeptidase (GGT), GGT to platelet ratio (GPR), pediatric end‐stage liver disease score, AST to platelet ratio index, and spleen size, and a negative correlation with albumin and platelet count in BA, with similar correlations for A1ATD (except AST, ALT, and albumin) and ALGS (except for INR, GGT, GPR, and ALT). Possible or definite CEPH was more common in BA compared to ALGS and A1ATD. LSM was greater in definite versus absent CEPH in all three diseases. Disease‐specific clinical and biochemical characteristics of the different CEPH grades were observed. Conclusion: It is feasible to obtain LSMs in children, especially over the age of 2 years. LSM correlates with liver parameters and portal hypertension, although disease‐specific patterns exist.

Updates in non-alcoholic fatty liver disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in childhood. There is an increase in disease prevalence and diagnoses as it is difficult to diagnose the problem. There are currently no effective medications. Management of NAFLD is a challenge for primary care clinicians and subspecialists. This paper provides guidelines for disease screening, diagnosis, management, and algorithm for subspecialty referral.