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Background and aims: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers, and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international cohort of children with ALGS. Approach and results: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18-year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced >= 1 adverse liver-related event (CEPH, transplant, or death). Children (>6 and = 5.0 and = 10.0 mg/dl had an 8.0-fold (95% CI, 3.4-18.4) increased risk of developing CEPH compared with those 10.0 mg/dl were associated with a 4.8 (95% CI, 2.4-9.7) and 15.6 (95% CI, 8.7-28.2) increased risk of transplantation relative to = 5.0 mg/dl, with 79% reaching adulthood with native liver (p < 0.001). Conclusions: in this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB, This study received funding support from the following agencies: The Alagille Syndrome Alliance, Mirum Pharmaceuticals Inc. and Albireo Pharma, Inc. who provided unrestricted educational grants to the Hospital for Sick Children (SickKids Foundation). The study sponsors were not involved in the conduct of the research study or preparation of the manuscript.

Based on systematic review and meta-analysis, the risk for developing cancers in patients with cystic fibrosis (CF) is known to be significantly greater than in the general population, including site-specific cancers of the esophagus, small bowel, colon, liver, biliary tract, and pancreas. An even higher risk has been found in patients who have severe CF transmembrane conductance regulator (CFTR) genotypes or who have undergone organ transplantation and are immunosuppressed. The risk continues to rise as life expectancies steadily climb due to advancements in medical care and treatment for CF. The colorectal cancer risk is at such a high level that CF has now been declared a hereditary colon cancer syndrome by the Cystic Fibrosis Foundation. The CFTR gene has been strongly-associated with the development of gastrointestinal (GI) cancers and mortality in the CF population. Even CF carriers have shown an increased rate of GI cancers compared to the general population. Several limitations exist with the reported guidelines for screening of GI and hepatopancreatobiliary cancers in the CF population, which are largely universal and are still emerging. There is a need for more precise screening based on specific risk factors, including CFTR mutation, medical co-morbidities (such as gastroesophageal reflux disease, distal intestinal obstruction syndrome, and diabetes mellitus), familial risks for each cancer, gender, age, and other factors. In this review, we propose changes to the guidelines for GI screening of patients with CF. With the development of CFTR modulators, additional studies are necessary to elucidate if there is an effect on cancer risk.

BACKGROUND Chilaiditi syndrome is a rare disorder characterized by the hepatodiaphragmatic interposition of the intestine. CASE SUMMARY Here we report a case of a 12-year-old male who was admitted to the pediatric intensive care unit secondary to abdominal pain and severe respiratory distress. He was treated conservatively but the symptoms persisted requiring a surgical approach. While there have been several cases of Chilaiditi syndrome reported in adults, there is a scarcity of cases reported in the pediatric population. Our review of the literature found only 30 pediatric cases, including our reported case, with Chilaiditi syndrome, 19 (63%) of which were male. The median age of diagnosis was 4.5 years old with an interquartile range of 2.0-10.0 years. In our review, we found that the most common predisposing factors in children are aerophagia (12/30 cases) and constipation (13/30 cases). Ninety percent of the cases presented with complete intestinal interposition, in 100% of which, the colon was involved. Three of the 30 cases were associated with volvulus. CONCLUSION In the pediatric population, conservative (21/30 cases) and surgical (8/30 cases) treatment approaches have produced satisfactory outcomes for all the patients, regardless of approach.

Methods to identify children with cystic fibrosis (CF) at risk for development of advanced liver disease are lacking. We aim to determine the association between liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) with research ultrasound (US) patterns and conventional hepatic markers as a potential means to follow liver disease progression in children with CF. ELASTIC (Longitudinal Assessment of Transient Elastography in CF) is a nested cohort of 141 patients, ages 7-21, enrolled in the Prediction by US of Risk of Hepatic Cirrhosis in CF (PUSH) Study. We studied the association between LSM with research-grade US patterns (normal [NL], heterogeneous [HTG], homogeneous [HMG], or nodular [NOD]) and conventional hepatic markers. In a subgroup (n = 79), the association between controlled attenuation parameter (CAP) and US pattern was explored. Among 133 subjects undergoing VCTE, NOD participants (n = 26) had a significantly higher median (interquartile range) LSM of 9.1 kPa (6.3, 15.8) versus NL (n = 72, 5.1 kPa [4.2, 7.0]; P

Background & Aims A practical, inexpensive, and non-invasive biomarker of liver fibrosis is needed as a reliable screening test for cystic fibrosis-associated liver disease (CFLD). Studies have shown the utility of AST to Platelet Ratio Index (APRI), fibrosis index based on 4 factors (FIB-4), and gamma-glutamyl transferase (GGT) as good biomarkers for identifying CFLD. The goal of the study was to evaluate the effectiveness of APRI, FIB-4, AST/ALT ratio, platelet count, GGT, and GGT platelet ratio (GPR) in predicting CFLD development. Methods Data was collected from CF Foundation Patient Registry for patients aged 3–21 years at Johns Hopkins from January 1, 2002 to December 31, 2014. Collected data included demographic characteristics, presence of splenomegaly, hepatomegaly, ascites, and variceal bleeding, AST, ALT, GGT, platelet count, and FEV1. The sensitivity and specificity of each biomarker were analyzed and reported by the area under receiver operating characteristic (AUROC) curve. Results By the end of the study, 144 “healthy” CF, 12 CFLD, 19 CF-associated pulmonary disease (CFPD), and 4 CFLD with CFPD cases were identified. APRI scores were higher in CFLD, 0.85 versus 0.28 in “healthy” CF and 0.23 in CFPD groups (p Conclusions GPR, GGT, APRI score, and platelet count were potentially useful biomarkers while FIB-4 did not predict CFLD development. Cost-effectiveness studies are needed to analyze the utility of these biomarkers in clinical practice.

Coronavirus disease 2019 (COVID-19) is a severe respiratory disease caused by the virus SARS-CoV-2 that became classified as a pandemic on March 11, 2020. COVID-19 is known to produce similar clinical manifestations to SARS of the last decade. Fever, dry cough, fatigue, myalgia, dyspnea, and sore throat are some of the most common symptoms and the median incubation period is around 4 days. While the respiratory manifestations have been widely reported, clinical manifestations on the gastrointestinal and hepatic side have often been overlooked. Diarrhea and nausea or vomiting have been reported in approximately 1-5% of cases and sometimes they precede respiratory symptoms. COVID-19 has also been reported to cause hemorrhagic colitis in one case Live SARS-CoV-2 have been detected in stool so, there is a possibility of fecal-oral transmission thus it recommended that non-urgent and low prior endoscopies be postponed. For endoscopies that cannot be postponed, SARS-CoV-2 screening of patients, minimal personnel, infection control training, and usage of negative pressure rooms are recommended. Evidence of abnormal liver-associated biomarker values have been commonly reported, however, there is evidence of extrahepatic causes those abnormal biomarker values. The evidence suggest that COVID-19 patients can have true liver injury, however, it is mild and the abnormal liver-associated biomarker values may be caused, at least partially, but muscle injury. Drugs with hepatotoxicity should be used with increased caution in COVID-19 patients.

Hepatitis E is a major cause of acute viral hepatitis in the world. The causative agent of hepatitis E is hepatitis E virus (HEV). In Southeast Asia, the seroprevalence of HEV and the most prevalent genotype of HEV are largely unclear and the available data is either limited or outdated. After a systematic review of literature, we found the seroprevalence of HEV and the most prevalent genotype of HEV appear to vary greatly by countries. The seroprevalence is likely between 17% to 42% and the prevalent genotypes across Southeast Asia are likely 1, 3, and 4, but not 2 as no cases of genotype 2 have been reported in this region. As HEV remains widespread in Southeast Asia and the clinical implications of HEV can be severe, surveillance programs for HEV should be implemented.

In the United States, hepatitis D is not a reportable condition, leading to gaps in epidemiological and clinical knowledge. We aim to estimate the incidence of hepatitis D-associated hospitalizations in the United States and describe the clinical, demographic and geographic characteristics of those hospitalizations. We utilized hospitalization data from the 2010-2018 National Inpatient Sample from the Healthcare Cost and Utilization Project. Hepatitis D and hepatitis B only (HBV only) hospitalizations were identified by International Classification of Diseases, Ninth Revision (ICD-9) and International Classification of Diseases, Tenth Revision (ICD-10) codes. We identified 3825 hepatitis D-associated hospitalizations. The hospitalization rate of hepatitis D was between 6.9 and 20.7 per 10,000,000 but did not change significantly over time. Compared to HBV only, the hepatitis D cohort had a greater proportion of males, Hispanics, hospitalizations in the Northeast region. The hepatitis D-associated hospitalizations also had significantly greater frequencies of liver failure, non-alcoholic cirrhosis, portal hypertension, ascites and thrombocytopenia. While mortality in hepatitis D was similar to that of HBV only, age65 years (odds ratio [OR] = 3.79; p = .020) and having a diagnosis of alcoholic cirrhosis (OR = 3.37; p = .044) increased the odds of mortality within the hepatitis D cohort. Although the hepatitis D-associated hospitalizations were relatively uncommon, they were associated with severe complications.

Mutations in ATP8B1 can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1 (PFIC1). 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 novel insights by using the largest genetically defined cohort of FIC1 deficiency patients to date. 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 PPTM), 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 18y. NLS was comparable between FIC1-A, FIC1-B, and FIC1-C (%NLS at age 10y: 67%, 41%, and 59%, respectively; P=0.12), despite FIC1-C undergoing SBD less often (%SBD at age 10y: 65%, 57%, and 45%, respectively; P=0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10y; sBAs, University of Colorado; Baylor College of Medicine; Children’s Hospital of Philadelphia; Children’s Hospital of Pittsburgh; St Louis Children’s Hospital; Riley Hospital for Children; Seattle Children’s Hospital; M.D./Ph.D. Scholarship from the University of Groningen; European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Networking Grant 2019; ChilDReN National Institutes of Health Grants; Ann & Robert H. Lurie Children’s Hospital; Albireo and Mirum Pharmaceuticals

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract that mainly affects young people. IBD is associated with various gastrointestinal symptoms, and thus, affects the quality of life of patients. Currently, the pathogenesis of IBD is poorly understood. Although intestinal bacteria and host immune response are thought to be major factors in its pathogenesis, a sufficient explanation of their role in its pathophysiologic mechanism has not been presented. MicroRNAs (miRNAs), which are small RNA molecules that regulate gene expression, have gained attention as they are known to participate in the molecular interactions of IBD. Recent studies have confirmed the important role of miRNAs in targeting certain molecules in signaling pathways that regulate the homeostasis of the intestinal barrier, inflammatory reactions, and autophagy of the intestinal epithelium. Several studies have identified the specific miRNAs associated with IBD from colon tissues or serum samples of IBD patients and have attempted to use them as useful diagnostic biomarkers. Furthermore, some studies have attempted to treat IBD through intracolonic administration of specific miRNAs in the form of nanoparticle. This review summarizes the latest findings on the role of miRNAs in the pathogenesis, diagnosis, and treatment of IBD.

Background Disaccharides such as lactose and sucrose are sugars commonly found in human diet. They are broken down by mucosal disaccharidases in the duodenum. Previous small studies found no associations between gastrointestinal (GI) symptoms and combined low disaccharidase activity. We aim to explore the associations of low activity of disaccharidase and combinations of low activity of different disaccharidases with general GI symptom presentations in a large cohort of pediatric patients. Methods We examined a cohort (0–21 yrs.) who have undergone esophagogastroduodenoscopy and received disaccharidase activity assay from duodenal biopsy in the time period 2010 to 2012. Disaccharidase assays tested for activity of lactase, sucrase, maltase, and palatinase. GI symptoms were grouped into four categories, abdominal pain, diarrhea, weight loss, and gastroesophageal reflux. Results Of the 347 subjects, we found an association between low lactase activity and abdominal pain (OR = 1.78; 95% CI = 1.07–2.97; p p Conclusions Low activities of certain disaccharidase combinations may be associated with GI symptoms in subjects; a prospective study may be needed to investigate further.

To assess if a heterogeneous pattern on research liver ultrasound examination can identify children at risk for advanced cystic fibrosis (CF) liver disease.Planned 4-year interim analysis of a 9-year multicenter, case-controlled cohort study (Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF). Children with pancreatic insufficient CF aged 3-12 years without known cirrhosis, Burkholderia species infection, or short bowel syndrome underwent a screening research ultrasound examination. Participants with a heterogeneous liver ultrasound pattern were matched (by age, Pseudomonas infection status, and center) 1:2 with participants with a normal pattern. Clinical status and laboratory data were obtained annually and research ultrasound examinations biannually. The primary end point was the development of a nodular research ultrasound pattern, a surrogate for advanced CF liver disease.There were 722 participants who underwent screening research ultrasound examination, of which 65 were heterogeneous liver ultrasound pattern and 592 normal liver ultrasound pattern. The final cohort included 55 participants with a heterogeneous liver ultrasound pattern and 116 participants with a normal liver ultrasound pattern. All participants with at least 1 follow-up research ultrasound were included. There were no differences in age or sex between groups at entry. Alanine aminotransferase (42 ± 22 U/L vs 32 ± 19 U/L; P = .0033), gamma glutamyl transpeptidase (36 ± 34 U/L vs 15 ± 8 U/L; P .001), and aspartate aminotransferase to platelet ratio index (0.7 ± 0.5 vs 0.4 ± 0.2; P .0001) were higher in participants with a heterogeneous liver ultrasound pattern compared with participants with a normal liver ultrasound pattern. Participants with a heterogeneous liver ultrasound pattern had a 9.1-fold increased incidence (95% CI, 2.7-30.8; P = .0004) of nodular pattern vs a normal liver ultrasound pattern (23% in heterogeneous liver ultrasound pattern vs 2.6% in normal liver ultrasound pattern).Research liver ultrasound examinations can identify children with CF at increased risk for developing advanced CF liver disease.

Provide a brief summary of your article (100 to 150 words; no references or figures/tables). The synopsis appears only in the table of contents and is often used by indexing services such as PubMed Chronic viral hepatitis continues to be a global health threat and a financial burden. Hepatitis B and C viruses (HBV and HCV) are the most common causes of chronic viral hepatitis in the United States. The majority of cases are asymptomatic during childhood and young adulthood. Cirrhosis and hepatocellular carcinoma are rare during childhood but commonly expected in adulthood. Efforts from worldwide health organizations, pharmaceutical industries, and clinical and research institutions have resulted in much new knowledge, very effective therapy for HCV-infected children and the promise of new effective therapies for HBV-infected children. For HCV-infected children the current standard of care is pegylated interferon and ribavirin but clinical trials with highly effective direct acting antiviral agents are currently underway in the pediatric age group. There are currently 5 FDA-approved agents for HBV-infected children: alpha-interferon, lamivudine, adefovir, tenofovir, and entecavir. However treatment with these agents seldom results in a functional cure and more effective therapies are urgently needed

Objectives Early identification of children with cystic fibrosis (CF) at risk for severe liver disease (CFLD) would enable targeted study of preventative therapies. There is no gold standard test for CFLD. Ultrasonography (US) is used to identify CFLD, but with concerns for its diagnostic accuracy. We aim to determine if differences in standard blood tests, imaging variables and noninvasive liver fibrosis indices correlate with liver US patterns, and thus provide supportive evidence that a heterogeneous US liver pattern reflects clinically relevant liver disease. Methods We studied baseline research abdominal US and bloodwork from 244 children with pancreatic insufficient CF, ages 3 to 12 years, enrolled in a prospective study of the ability of US to predict CF cirrhosis (PUSH study). Children with a heterogeneous (HTG) liver pattern on US (n = 62) were matched 1 : 2 in design with children with normal US (NL, n = 122). Analyses included children with nodular (NOD, n = 22) and homogeneous hyperechoic (HMG, n = 38) livers. Results Univariate analysis showed significant differences between US groups for standard blood tests, spleen size, and noninvasive liver fibrosis indices. Multivariable models discriminated NOD versus NL with excellent accuracy (AUROC 0.96). Models also distinguish HTG versus NL (AUROC 0.76), NOD versus HTG (0.78), and HMG versus NL (0.79). Conclusions Liver US patterns in children with CF correlate with platelet count, spleen size and indices of liver fibrosis. Multivariable models of these biomarkers have excellent discriminating ability for NL versus NOD, and good ability to distinguish other US patterns, suggesting that US patterns correlate with clinically relevant liver disease.

OBJECTIVES α-1-Antitrypsin (A1AT) deficiency is a common genetic disease with an unpredictable and highly variable course. The Childhood Liver Disease Research and Education Network is a National Institutes of Health, multicenter, longitudinal consortium studying pediatric liver diseases, with the objective of prospectively defining natural history and identifying disease modifiers. METHODS Longitudinal, cohort study of A1AT patients' birth through 25 years diagnosed as having liver disease, type PIZZ or PISZ. Medical history, physical examination, laboratory, imaging, and standardized survey tool data were collected during the provision of standard of care. RESULTS In the present report of the cohort at baseline, 269 subjects were enrolled between November 2008 and October 2012 (208 with their native livers and 61 postliver transplant). Subjects with mild disease (native livers and no portal hypertension [PHT]) compared to severe disease (with PHT or postliver transplant) were not different in age at presentation. A total of 57% of subjects with mild disease and 76% with severe disease were jaundiced at presentation (P = 0.0024). A total of 29% of subjects with native livers had PHT, but age at diagnosis and growth were not different between the no-PHT and PHT groups (P > 0.05). Subjects with native livers and PHT were more likely to have elevated bilirubin, ALT, AST, INR, and GGTP than the no-PHT group (P <

Hepatitis E virus (HEV) is an emerging cause of viral hepatitis among immunocompromised individuals in developed countries. Yet the diagnosis of HEV infection in the United States remains challenging, because of the variable sensitivity and specificity of currently available tests, and the lack of a US Food and Drug Administration-approved test. We report a case of multiple discordant HEV serology results in a pediatric liver transplant recipient with idiopathic hepatitis, and review the challenges to diagnosis of HEV infection in the United States.

Cirrhosis occurs in 5% to 10% of cystic fibrosis (CF) patients, often accompanied by portal hypertension. We analyzed 3 adverse liver outcomes, variceal bleeding (VB), liver transplant (LT), and liver-related death (LD), and risk factors for these in CF Foundation Patient Registry subjects with reported cirrhosis.We determined 10-year incidence rates for VB, LT, LD, and all-cause mortality (ACM), and examined risk factors using competing risk models and Cox-proportional hazard regression.From 2003 to 2012, 943 participants (41% females, mean age 18.1 years) had newly reported cirrhosis; 24.7% required insulin, 85% had previous pseudomonas. Seventy-three subjects had reported VB: 38 with first VB and new cirrhosis reported simultaneously and 35 with VB after cirrhosis report. Ten-year cumulative VB, LT, and LD rates were 6.6% (95% confidence interval [CI]: 4.0, 9.1%), 9.9% (95% CI: 6.6%, 13.2%), and 6.9% (95% CI: 4.0%, 9.8%), respectively, with an ACM of 39.2% (95% CI: 30.8, 36.6%). ACM was not increased in subjects with VB compared to those without (hazard ratio [HR] 1.10, 95% CI: 0.59, 2.08). CF-related diabetes (HR: 3.141, 95% CI:1.56, 6.34) and VB (HR: 4.837, 95% CI: 2.33, 10.0) were associated with higher LT risk, whereas only worse lung function was associated with increased LD in multivariate analysis. Death rate among subjects with VB was 24% with LT and 20.4% with native liver.VB is an uncommon complication of CF cirrhosis and can herald the diagnosis, but does not affect ACM. Adverse liver outcomes and ACM are frequent by 10 years after cirrhosis report.

To assess neurodevelopmental outcomes among participants with biliary atresia with their native liver at ages 12 months (group 1) and 24 months (group 2), and to evaluate variables predictive of neurodevelopmental impairment.Participants enrolled in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with either the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition. Scores (normative mean = 100 ± 15) were categorized as ≥100, 85-99, and85 for χThere were 148 children who completed 217 Bayley Scales of Infant and Toddler Development, 3rd edition, examinations (group 1, n = 132; group 2, n = 85). Neurodevelopmental score distributions significantly shifted downward compared with test norms at 1 and 2 years of age. Multivariate analysis identified ascites (OR, 3.17; P = .01) and low length z-scores at time of testing (OR, 0.70; P .04) as risk factors for physical/motor impairment; low weight z-score (OR, 0.57; P = .001) and ascites (OR, 2.89; P = .01) for mental/cognitive/language impairment at 1 year of age. An unsuccessful hepatoportoenterostomy was predictive of both physical/motor (OR, 4.88; P .02) and mental/cognitive/language impairment (OR, 4.76; P = .02) at 2 years of age.Participants with biliary atresia surviving with native livers after hepatoportoenterostomy are at increased risk for neurodevelopmental delays at 12 and 24 months of age. Those with unsuccessful hepatoportoenterostomy are4 times more likely to have neurodevelopmental impairment compared with those with successful hepatoportoenterostomy. Growth delays and/or complications indicating advanced liver disease should alert clinicians to the risk for neurodevelopmental delays, and expedite appropriate interventions.Clinicaltrials.gov: NCT00061828 and NCT00294684.

Amac: Colyak hastal›¤› taramas›nda, anti-gliadin immunglobulin G ve A antikorlar›n›n kullan›m›, doku transglutaminaz ve endomisyal antikorlar›n daha yuksek olan duyarl›l›k ve ozgullu¤u nedeniyle giderek azalmaktad›r. Kan›tlanm›fl ve muhtemel colyak hastal›¤› olgula- r›nda, yuksek anti-gliadin immunglobulin A deerleri daha ciddi mukozal hasarla iliflkilidir. Cal›flman›n amac›, anti-gliadin immunglob- ulin A'n›n cocuklarda colyak hastal›¤› tan›s› konmas›nda klinik onemi olup olmad›¤›n› tespit etmektir. Gerec ve Yontem: Poliklinie kro- nik kusma, kar›n ar›s›, ishal veya kab›zl›k hikayesiyle baflvuran cocuklar, colyak hastal›¤› ac›s›ndan deerlendirildi. Serum doku transglu- taminaz ve anti-gliadin immunglobulin A duzeyleri, EL‹SA testiyle, endomisyal antikor immunoglobulin A ise indirek immunofloresans yon- temiyle tespit edildi. Anti-gliadin immunglobulin A sonucu pozitif olan cocuklar›n couna ileri tetkik olarak proksimal gastrointestinal bi- yopsi yap›ld›. Bulgular: Onalt› cocukta, izole anti-gliadin immunglobulin A pozitiflii (negatif doku transglutaminaz ve endomisyal anti- kor immunoglobulin A) saptand›. Sekiz tanesi erkekti (ortalama yafl, 9.7). Hicbirisinde immunoglobulin A yetmezlii yoktu. Onuc tanesin- den, ust endoskopi ile cok say›da ince barsak biyopsisi al›nd›. ‹ki hastada villoz atrofi ve intraepitelial lenfosit say›s›nda hafif art›fl (Marsh 3a) ile muhtemel colyak hastal›¤› tan›s› kondu. Bu iki hastada anti-gliadin immunglobulin A titresi 70 unitenin uzerindeydi. Sonuc: Doku transglutaminaz ve endomisyal antikor immunoglobulin A pozitiflii olmad›¤›nda, izole anti-gliadin immunglobulin A pozitiflii olmas› du- rumunda, colyak hastal›¤› tan›s› ihtimali duflunulmelidir. Bu latent colyak hastal›¤› veya gluten hipersenstivitesi gibi durumlarda olabile- cek non-spesifik bir durum olabilir. Bu cocuklarda uzun sureli klinik takip, tan›n›n kesinlefltirilmesi icin onerilmektedir. Anahtar kelimeler: ‹zole anti-gliadin immunglobulin A antikoru, negatif doku transglutaminaz ve endomisyal antikorlar›, colyak hastal›¤›; Marsh s›n›flamas›; gastrointestinal semptomlar, gluten hipersenstivitesi Background/aims: The use of immunoglobulin G and A anti-gliadin antibodies for celiac disease screening has decreased due to higher spe- cificity and sensitivity of tissue transglutaminase and endomysial antibodies. Greater values of immunoglobulin-A anti-gliadin antibody ha- ve been associated with more severe mucosal damage in proven and probable celiac disease patients. The aim of this study was to determine whether anti-gliadin antibody immunoglobulin A has any clinical importance in diagnosing celiac disease in children. Children with a chro- nic history of vomiting, abdominal pain, diarrhea, or constipation in the outpatient clinic were evaluated for celiac disease. Materials and Methods: Tissue transglutaminase and anti-gliadin antibody immunoglobulin A in serum were determined by ELISA test and endomysial antibodies immunoglobulin A by indirect immunofluorescence. Most of these children with isolated positive anti-gliadin antibody immunog- lobulin A were further evaluated by performing proximal gastrointestinal biopsies. Results: Sixteen children had isolated positive anti-glia- din antibody immunoglobulin A (negative tissue transglutaminase and endomysial antibodies immunoglobulin A). Eight were male (mean age: 9.7 years). None had immunoglobulin A deficiency. Thirteen underwent an upper endoscopy with multiple small bowel biopsies. Two pa- tients had villous atrophy and slightly increased intraepithelial lymphocytes (Marsh 3a), which could make the diagnosis of celiac disease li- kely. These two patients had high titers of anti-gliadin antibody immunoglobulin A above 70 Units. Conclusions: An isolated positive anti- gliadin antibody immunoglobulin A result in the absence of positive tissue transglutaminase and endomysial antibodies immunoglobulin A should raise the suspicion of the diagnosis of celiac disease. This could be a non-specific phenomenon that could be found in other gastroin- testinal conditions, latent celiac disease, or gluten hypersensitivity. A longitudinal clinical follow-up is recommended in these children to con- firm the diagnosis.

An 18-month-old female status post-orthotopic liver transplant for biliary atresia presented nine months after transplant with severe diarrhea and intolerance of feeds. She was found to have a PLE as evidenced by a low serum albumin and a persistent elevation of fecal A1AT. Investigation eventually revealed that the cause of the PLE was a stricture at the anastomosis site between the hepatic vein and inferior cava, supported by resolution of the PLE after venoplasty of the stricture. The patient has subsequently required several repeat venoplasties for recurrence of her symptoms correlating with recurrence of the stricture. This is a very rare presentation of hepatic venous outflow obstruction. Moreover, normal duplex ultrasound imaging of liver vasculature and her unusual presentation led to a delay in her diagnosis highlighting the need for an increased index of suspicion.

Wikrom Karnsakul, Mary Kay Alford, Kathleen B SchwarzPediatric Liver Center, Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins School of Medicine, Baltimore, MD, USAAbstract: Since 1992, the maternal–fetal route of transmission has become the dominant route for acquisition of hepatitis C (HCV) infection by children. With increasing knowledge of antiviral treatment for HCV infection, the main goal of therapy is to achieve a sustained virological response (SVR) as defined by undetectable serum HCV RNA by polymerase chain reaction assay six months after cessation of therapy. In young children, interferon therapy is more effective than in adults with chronic HCV infection (CHC). Although children clearly have a milder degree of liver pathology, data have indicated that hepatic inflammation from HCV infection can progress to fibrosis or cirrhosis in children. Hepatocellular carcinoma has been reported in adolescents with CHC. In this article, recent improvements in therapy of children with CHC and in the clinical development of new emerging drugs with potential use in children will be reviewed.Keywords: chronic hepatitis C, children, current therapy, pegylated interferon