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Background: Cholestatic disorders are a significant cause of morbidity and mortality in infants. Characterization of these disorders and differentiating biliary atresia (BA) from other causes of intrahepatic cholestasis is an age-old problem. Objectives: To study the spectrum of different infantile cholestatic disorders in our population, to differentiate BA from other causes of neonatal cholestasis (NC) on a liver biopsy, and validation of the available scoring system for the characterization of these disorders. Materials and Methods: This is an observational cross-sectional study performed over a period of 3 years between 2018 and 2021, done on neonates and infants presenting with cholestatic jaundice. The changes on liver biopsy were evaluated by different histological parameters and available scoring systems to differentiate BA from non-BA causes. Correlation with clinical, biochemical, and imaging findings was done in all cases. Results: This study included 87 cases of NC, of which BA comprised 28 cases (32%), whereas idiopathic neonatal hepatitis (INH) comprised only 12 cases (14%). Portal neutrophilic inflammation (P = 0.000053), ductal cholestasis (P < 0.001), neoductular bile plugs (P < 0.001) and bile ductular proliferation (P < 0.0001) were significantly more in BA, whereas lobular lymphocytic inflammation (P = 0.001) and giant cell transformation of hepatocytes (P = 0.0024) were more frequent in the non-BA group. Using the Lee and Looi scoring system, a histologic score ≥7 was helpful in identifying BA with 85.7% sensitivity, 92.6% specificity, and 90.6% accuracy. Conclusion: BA is the commonest cause of NC in neonates, whereas the frequency of INH is declining. Detailed histomorphologic analysis of liver biopsy, aided with IHC, is the cornerstone for the diagnosis of these disorders.

Reports on the clinical course of fetal umbilical vein varix in premature infants are limited. We report a case of an extremely low body weight infant with intra-abdominal umbilical vein varix who developed disseminated intravascular coagulation, polycythemia, and hyperbilirubinemia after birth; late-onset neonatal hepatitis; and fetal thrombotic vasculopathy confirmed by placental histopathology. Ultrasonography after birth showed a dilated portion of the umbilical vein at the hepatic hilum with thrombi inside. We speculate that the umbilical vein varix caused the fetal thrombotic vasculopathy, and the presence of umbilical vein varix and fetal thrombotic vasculopathy in combination with prematurity caused coagulopathy, polycythemia, hyperbilirubinemia, and hepatitis. Despite the favorable outcomes reported in the literature, premature infants with umbilical vein varix may require careful observation and management for coagulopathy and late-onset hepatitis. Furthermore, placental histopathology could aid in the understanding of various clinical outcomes in infants with umbilical vein varices.

Background: Differentiation of neonatal cholestasis into neonatal hepatitis (NH) and extrahepatic biliary atresia (EHBA) is essential to formulate the treatment plan; promptness is indispensable for optimal outcomes. The clinical and nonoperative algorithms lack precision; the gold standard investigations (liver biopsy or per-operative cholangiogram) are invasive. There is a need for a noninvasive test which is both, sensitive and specific and has a high likelihood ratio. Aim: To study the (diagnostic) role of matrix metalloproteinase 7 (MMP-7) as a serum biomarker to differentiate between EHBA and NH and evaluate the prognostic significance in EHBA based on its correlation with liver histopathology and serological predictors of liver fibrosis – Aspartate-to-Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4). Materials and Methods: This was a prospective study conducted upon patients of neonatal cholestasis presenting with acholic stools (n = 46) with equal number of controls (n = 45) with no liver pathology. Observational parametric included disease-specific workup and serum MMP-7 levels (all participants); liver biopsyl and APRI-FIB-4 (EHBA). Results: (Diagnostic) Serum MMP-7 levels were significantly elevated in EHBA (n = 25; 28 ng/mL) as compared to those in NH (n = 21; 1.88 ng/mL) and normal infants (n = 45; 1.2 ng/mL) (P < 0.001 for both). Serum cutoff at 4.99 ng/mL differentiated EHBA-NH with a high sensitivity (96%), specificity (90.5%), and a negative predictive value (95%), with the number needed to misdiagnose being 23. (Prognostic) Inflammatory activity and fibrosis-stage on liver histopathology (METAVIR-and-Ishak scores) correlated with MMP-7 levels. APRI and FIB-4 scores also depicted a strong correlation with each other, age of the patient, and liver fibrosis. Conclusions: MMP-7 has a diagnostic value in differentiating EHBA from NH and may also be used as a prognostic biomarker in the follow-up of these patients. MMP-7 levels in controls may be used as a baseline for future studies.

Background: Differentiation of neonatal cholestasis into neonatal hepatitis (NH) and extrahepatic biliary atresia (EHBA) is essential to formulate the treatment plan; promptness is indispensable for optimal outcomes. The clinical and nonoperative algorithms lack precision; the gold standard investigations (liver biopsy or per-operative cholangiogram) are invasive. There is a need for a noninvasive test which is both, sensitive and specific and has a high likelihood ratio. Aim: To study the (diagnostic) role of matrix metalloproteinase 7 (MMP-7) as a serum biomarker to differentiate between EHBA and NH and evaluate the prognostic significance in EHBA based on its correlation with liver histopathology and serological predictors of liver fibrosis – Aspartate-to-Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4). Materials and Methods: This was a prospective study conducted upon patients of neonatal cholestasis presenting with acholic stools (n = 46) with equal number of controls (n = 45) with no liver pathology. Observational parametric included disease-specific workup and serum MMP-7 levels (all participants); liver biopsyl and APRI-FIB-4 (EHBA). Results: (Diagnostic) Serum MMP-7 levels were significantly elevated in EHBA (n = 25; 28 ng/mL) as compared to those in NH (n = 21; 1.88 ng/mL) and normal infants (n = 45; 1.2 ng/mL) (P < 0.001 for both). Serum cutoff at 4.99 ng/mL differentiated EHBA-NH with a high sensitivity (96%), specificity (90.5%), and a negative predictive value (95%), with the number needed to misdiagnose being 23. (Prognostic) Inflammatory activity and fibrosis-stage on liver histopathology (METAVIR-and-Ishak scores) correlated with MMP-7 levels. APRI and FIB-4 scores also depicted a strong correlation with each other, age of the patient, and liver fibrosis. Conclusions: MMP-7 has a diagnostic value in differentiating EHBA from NH and may also be used as a prognostic biomarker in the follow-up of these patients. MMP-7 levels in controls may be used as a baseline for future studies. [ABSTRACT FROM AUTHOR]

Background: Neonatal cholestasis (NC) is a major cause of morbidity and mortality in young infants. This study examines the etiology of NC and its outcome during 2 years of follow-up at a tertiary referral center in Bangladesh. Results: Out of 80 cholestatic infants, 60% had intrahepatic cholestasis with a mean age of onset of 12.4±2.8 days and a mean age of admission of 82.4±29.0 days. The remaining 40% were extrahepatic with a mean age of onset of 6.7±2.3 days and a mean age of admission of 94.6±50.4 days. Biliary atresia (BA), idiopathic neonatal hepatitis (INH), and TORCH (Toxoplasma, rubella, cytomegalovirus, and herpes simplex) infection except rubella were the most common causes. After receiving treatment, 46.2% of the cases improved, 23.8% deteriorated with morbidity, and 30% died. The majority of the children with INH, TORCH, choledochal cyst, hypothyroidism, galactosemia, and urinary tract infection (UTI) with sepsis were improved. Significant mortality was found in BA (56.6%), intrahepatic bile duct paucity (PIBD) (100%), and progressive familial intrahepatic cholestasis (PFIC) (100%) whereas the rest of BA (43.4%) live with persistent morbidity. Significant clinical improvement was observed in 37 (46.2%) cases of cholestasis evidenced by decreasing jaundice, change of color of urine from dark to normal color, change of stool color from pale to yellow, and gradual decrease in liver size from hepatomegaly state. In addition, decreasing median total bilirubin, direct bilirubin, alanine transaminase, gamma-glutamyl transferase, and alkaline phosphatase showed biochemical improvement at 2 years follow-up. The age of admission, etiology, and presence of ascites are the predictors of outcomes. Conclusion: BA was the most common cause of extrahepatic while INH and TORCH infection were the most common cause of intrahepatic cholestasis. Majority of children with intrahepatic cholestasis improved but deteriorated with BA and genetic causes. Prompt referral and early diagnosis as well as the etiology of NC were the main determinants of the favorable outcome. [ABSTRACT FROM AUTHOR]

Magd A Kotb,1 Iman Draz,1 Christine WS Basanti,1 Sally TM El Sorogy,2 Hesham M Abd Elkader,3 Haytham Esmat,4 Hend Abd El Baky,1 Dalia Sayed Mosallam1 1Pediatrics Department, Faculty of Medicine, Kasr Al Ainy, Cairo University, Cairo, Egypt; 2Pediatrics Department, Public Mounira Hospital, Cairo, Egypt; 3Department of Pediatric Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 4Department of Pediatric Surgery, Cairo University, Cairo, EgyptCorrespondence: Dalia Sayed MosallamPediatrics Department, Faculty of Medicine, Cairo University, Al Manial, Cairo 11562, EgyptTel +20 2 33386592Email daliamosalam@kasralainy.edu.egPurpose: We aimed to define the clinical presentations, course and outcome of cholestasis in infants with Down syndrome (trisomy 21) who presented to the Pediatric Hepatology Clinic, New Children Hospital, Cairo University, Egypt.Methods: Retrospective analysis of data of cohort of infants with Down syndrome and cholestasis who followed up during 2005–2015.Results: Among 779 infants with cholestasis who presented during 2005–2015, 61 (7.8%) had Down syndrome. Six dropped out. Among the 55 who followed-up for a mean duration +SD = 12.1 ± 16.7 months, none had extrahepatic biliary atresia (EHBA), 37 (63.3%) had neonatal hepatitis and 18 (32.7%) had non-syndromic paucity of intrahepatic biliary radicals. Fourteen (25.4%) had associated congenital heart disease. Only 35 (63.3%) cleared the jaundice. Twenty-nine (52.7%) received ursodeoxycholic acid (UDCA); of them, 13 cleared the jaundice, one improved, 14 progressed and one died, compared to 22 who cleared the jaundice of the 26 who did not receive UDCA. Only three of those who did not receive UDCA progressed and none died. UDCA carried a 3.4-fold risk of poor prognosis (p= 0.001). UDCA use was associated with more complications (p= 0.016) in those with Down syndrome and cholestasis.Conclusion: We did not come across EHBA among neonates and infants with Down syndrome in 10 years. Non-syndromic paucity is associated with favorable outcome in infants with Down syndrome. UDCA use in cholestasis with Down syndrome is associated with poor outcome.Keywords: cholestasis, extrahepatic biliary atresia, EHBA, neonatal hepatitis, Down syndrome, trisomy 21, ursodeoxycholic acid, UDCA

Background: Neonatal acute liver failure (ALF) is a severe condition with a mortality rate up to 70%. Human enterovirus (HEV) infections are associated with serious diseases in newborns, including myocarditis, meningoencephalitis and, more rarely, ALF with a fulminant course.Methods: Cases of neonatal-onset ALF were identified using the institutional clinical database. The history and clinical data of infants with HEV infection were collected by medical record revision. Viral testing by nested real- time PCR (nRT-PCR) was performed by the Bambino Gesù Children's Hospital Clinical Laboratory and by National Institute of Public Health in Rome.Results: Among ten infants referred to our Institution with neonatal-onset ALF in the 2004-2018 period, we identified five cases due to HEV. In three of these, the mother reported an episode of mild fever and diarrhea during the last trimester of gestation, suggesting fetal-maternal transmission. All were late preterm infants (32-36 weeks). Two infants died as a result of ALF; the other three survived with full normalization of liver function. In four, the causing agents were coxsackie B serotypes 3 (n = 1), 4 (n = 1) and 5 (n = 2), in the fifth case we identified echovirus serotype 11.Conclusions: Human enterovirus (HEV) are a rare but relevant cause of ALF in neonates. HEV testing should be systematically performed in cases of neonatal ALF for diagnostic and management purposes. [ABSTRACT FROM AUTHOR]

We report a 2-month-old male baby who presented with yellow discoloration of skin, high-colored urine, and intermittent clay-colored stools since 15 days of life. Head size was apparently looking large with dilated veins over the scalp. The baby was diagnosed and treated as neonatal herpes simplex virus hepatitis that led to cholestatic jaundice and cerebral aqueductal stenosis with hydrocephalus. It is a very rare association and less reported earlier in the literature.

Introduction: Neonatal Cholestasis syndrome is a common condition among infants that needs to be evaluated in detail to establish aetiology. Although Idiopathic neonatal hepatitis is common, clear outcome for same has not been established. Aim: To assess the clinical profile, aetiological spectrum of infants with Neonatal Cholestasis Syndrome (NCS) followed-up over 10 years. Materials and Methods: It was a retrospective study; data were collected from online records Jan 2008-Dec 2018. Total of 300 infants (210 males) were studied. Clinical outcome was assessed in non-surgical patients with a minimum of 6 month follow-up period. Chi-square test was used for statistical analysis. Results: Intrahepatic NCS was identified in 232 (77%)-majority 164 (54.6%) were idiopathic hepatitis. Remaining 68 (23%) had Extrahepatic NCS and Biliary Atresia (BA) was confirmed in 64 (21.3%). Mean age of presentation was 2.4 months in the intrahepatic group and 3 months in Extrahepatic NCS. All underwent blood tests and ultrasound. Liver biopsy was done in 72 (24%) -35 neonatal hepatitis (2 with cirrhosis), 24 BA, 11 Progressive Familial Intrahepatic Cholestasis, 1 bile duct paucity. All received multivitamin therapy till 1 year of age. Follow-up analysis done in 95 subjects at a mean age of 23.5 months (range 6-90) showed significant improvement in growth (weight centile from 8.9 to 27.7 and height centile from 16.7 to 22.4) and in liver function. Hepatobliary scan had a sensitivity of 90% in diagnosing Biliary Atresia. Conclusion: Idiopathic neonatal hepatitis is the most common aetiology in Neonatal hepatitis. Intrahepatic NCS has good outcome in terms of growth and normalisation of liver function.

Congenital Zika virus infection is associated with severe brain anomalies and impaired function. To determine outcomes, we followed 2 affected children for ≈30 months. For 1 who was symptomatic at birth, transient hepatitis developed. However, neurodevelopment for both children was age appropriate.

Abstract Purpose Biliary atresia is a life-threatening disease that needs early diagnosis and management. Recently, MRI images have been used for the diagnosis of biliary atresia with improved accuracy of diagnosis when other imaging modalities such as ultrasonography are equivocal. This study aimed to evaluate the juxta-hilar extrahepatic biliary tree using MRI images to determine a quantitative value for diagnosing biliary atresia. Materials and methods This retrospective study was approved by the Ethical Committee at Mackey Memorial Hospital (IRB Number: 15MMHIS149e). Between January 2010 and December 2015, twenty-five patients with surgically confirmed biliary atresia were enrolled (age 18–65 days). Another 25 patients with clinically or surgically diagnosed idiopathic neonatal hepatitis (age 6–64 days) and 20 patients with non-hepatobiliary disease (age 6–65 days) were considered control group and normal subjects, respectively. The diameter of the enlarged, T2-hyperintense structure was measured using MRI images by two radiologists both blinded. The cut-off value for a biliary atresia diagnosis was obtained by area under the curve analysis. Results The diameter of the T2-hyperintense structure at porta hepatis in biliary atresia (4.79 ± 1.14 mm) is larger than in idiopathic neonatal hepatitis (1.72 ± 0.42 mm) or in non-hepatobiliary disease (1.72 ± 0.35 mm) (p < 0.05). The optimum cut-off value for diagnosing biliary atresia was 3.1 mm with 98% sensitivity and 98% specificity. Conclusion The value of the enlarged, T2-hyperintense structure measured on MRI images was significantly increased in biliary atresia and may be useful in diagnosing biliary atresia. Highlights • MRI image can give more information for diagnosis of biliary atresia when other image findings are inconclusive. • Enlarged T2-weighted high signal at porta hepatis can distinguish biliary atresia from neonatal hepatitis. • A quantitative measurement in the MRI image may be helpful for diagnosis of biliary atresia. [ABSTRACT FROM AUTHOR]

In recent years, magnetic resonance imaging (MRI) has become more widely used in neonatal hypoxic-ischemic encephalopathy (HIE), involving, for example, evaluation of cerebral edema, white matter fiber bundle tracking, cerebral perfusion status, and assessment of brain metabolites. MRI has many imaging modalities. However, its application for assessing changes in the internal environment at the tissue and cellular level after hypoxia-ischemia remains a challenge and is currently the focus of intense research. Based on the exchange between amide protons of proteins and polypeptides and free water protons, amide proton transfer (APT) imaging can display changes in pH and protein concentrations in vivo. This paper is a review of the principles of APT imaging, with a focus on the potential application of APT imaging for neonatal HIE. [ABSTRACT FROM AUTHOR]

Although rare, ALF caused by disseminated HSV infection is associated with high mortality in the neonatal population. This condition is often diagnosed relatively late due to the absence of specific signs. We present a case involving a neonate with ALF submitted to living donor liver transplantation without a prior diagnosis. The patient had no skin or mucosal lesions, and IgM serology was negative for HSV-1 and HSV-2. Immunohistochemical staining of the liver explant was positive for herpes virus infection, and the patient subsequently received antiviral drug treatment, with a good outcome. Due to organ shortages and the rarity of the aforementioned condition, LT has seldom been reported for the treatment of ALF caused by herpes virus infection; however, LT may be the only option for neonates with fulminant hepatitis. The use of living donors in an urgent scenario is well established in Eastern countries and safely applicable for pediatric patients with ALF. [ABSTRACT FROM AUTHOR]

Even in the era of effective antiviral therapy, neonatal herpes simplex viral infection causes significant morbidity and mortality in newborns. Prompt diagnosis is the cornerstone of treatment of these infants. Outside and inside the neonatal clinical practice, polymerase chain reaction (PCR) is replacing culture as a method of facilitating a speedy diagnosis of herpes simplex virus infection. New pediatric guidelines call for testing of high-risk asymptomatic infants, and thus, many more surface cultures and PCRs are being performed. This review aims to comprehensively describe the perinatal transmission of herpes simplex virus infection and the clinical presentation of neonatal herpes simplex disease, as well as to discuss whether PCR remains superior to culture methods. [ABSTRACT FROM AUTHOR]

The neonatal crystallizable fragment receptor (FcRn) is responsible for maintaining the long half-life and high levels of the two most abundant circulating proteins, albumin and IgG. In the latter case, the protective mechanism derives from FcRn binding to IgG in the weakly acidic environment contained within endosomes of hematopoietic and parenchymal cells, whereupon IgG is diverted from degradation in lysosomes and is recycled. The cellular location and mechanism by which FcRn protects albumin are partially understood. Here we demonstrate that mice with global or liver-specific FcRn deletion exhibit hypoalbuminemia, albumin loss into the bile, and increased albumin levels in the hepatocyte. In vitro models with polarized cells illustrate that FcRn mediates basal recycling and bidirectional transcytosis of albumin and uniquely determines the physiologic release of newly synthesized albumin into the basal milieu. These properties allow hepatic FcRn to mediate albumin delivery and maintenance in the circulation, but they also enhance sensitivity to the albumin-bound hepatotoxin, acetaminophen (APAP). As such, global or liver-specific deletion of FcRn results in resistance to APAP-induced liver injury through increased albumin loss into the bile and increased intracellular albumin scavenging of reactive oxygen species. Further, protection from injury is achieved by pharmacologic blockade of FcRn-albumin interactions with monoclonal antibodies or peptide mimetics, which cause hypoalbuminemia, biliary loss of albumin, and increased intracellular accumulation of albumin in the hepatocyte. Together, these studies demonstrate that the main function of hepatic FcRn is to direct albumin into the circulation, thereby also increasing hepatocyte sensitivity to toxicity. [ABSTRACT FROM AUTHOR]

The most common conditions causing cholestatic jaundice in infants are biliary atresia, neonatal hepatitis, and Alagille syndrome. In these disorders, the clinical presentation includes jaundice, pale stools, dark urine and hepatomegaly. Splenomegaly is not an early feature since it is due to portal hypertension, a later event. The finding of cholestatic jaundice and a large spleen usually raises the suspicion of Niemann-Pick type C disease (NP-C), a lysosomal storage disorder. We present and discuss here a case of an infant with liver disease and splenomegaly that were not ascribed to NP-C, but to Gaucher disease type 2. Liver biopsy, enzymatic studies and whole exome sequencing allowed to make the diagnosis. Although rare, Gaucher disease can cause neonatal hepatitis. A prompt recognition is advocated. [ABSTRACT FROM PUBLISHER]

Background: Pathogenesis of neonatal hepatitis relates to various underlying causes including viral infections. Both hepatotropic and non-hepatotropic viruses may induce liver failures in infants before birth, during delivery, or shortly after birth.Objectives: The tissue impact of HCMV, HSV, HBV, HCV, and rotavirus and adenovirus infections was evaluated in studied infants with neonatal hepatitis.Methods: The history of viral infections was analyzed in paraffin-embedded biopsy and autopsy tissues of 22 infants with neonatal hepatitis between years 1996 and 2007, retrospectively. The tissue molecular presentation of HBV, HCV, HCMV, HSV, adenovirus, and rotavirus was evaluated by different qualitative simple and nested PCR and RT-PCR protocols. Immunohistochemistry (IHC) method was used for studying the antigenic prevalence of HSV-1, 2; HBV, HCMV and adenovirus infections. Also the laboratory liver indices of all patients with neonatal hepatitis were analyzed.Results: The HBV and HSV genomes were detected in 3 (14%) of 22 infants. The rotavirus and HCV-RNA and also the HCMV-DNA were detected separately in 1 (4%) of 26 paraffin-embedded autopsy and biopsy tissues. The HBV and HSV-1 specific antigens were separately diagnosed in 1 (4%) of 26 neonatal samples by IHC protocols. Also the HSV-2 antigen was seen in 5 (23%) of 22 liver autopsy and biopsy specimens. Co-infections with HCMV, HSV, HBV, HCV, and rotavirus were detected in these infants with hepatitis.Conclusion: Diagnosis of single and mixed molecular and antigenic traces of HCMV, HSV, HBV, HCV and rotavirus underlines the etiologic role of these viruses in clinical pathogenesis of neonatal hepatitis.

Objective: To evaluate the ultrasonography (US) features of Alagille syndrome (ALGS), as compared with biliary atresia (BA) or neonatal hepatitis (NH). Methods: Our study included 23 ALGS, 75 BA and 70 NH patients. The initial US images were retrospectively reviewed for gallbladder (GB) morphology with systemic classification, GB length and luminal area, presence of triangular-cord (TC) sign and hypertrophied hepatic-artery. The presence of anomalies associated with ALGS was evaluated. The diagnostic values of each finding and their combinations were evaluated. Results: Both ALGS (57%) and BA (79%) were more frequently associated with abnormal GB shapes than NH (19%, all P<0.001). The short and small GBs were more frequently observed in ALGS and BA than in NH (all P<0.001). None in the ALGS and NH showed TC sign, while 41% in the BA did (all P<0.001). Hypertrophied hepatic-artery was noted less frequently in both ALGS (13%) and NH (14%) than in BA (83%, all P<0.001). The combination of US criteria with associated anomalies increased the positive-predictive-value for ALGS. Conclusion: Abnormal shaped GB with absence of the TC sign and hypertrophied hepatic-artery and presence of associated anomalies can be a differential point of ALGS. [ABSTRACT FROM AUTHOR]

Accumulated data to date do not entirely explain the; propensity of the hepatitis B virus (HBV) to cause chronic infections in newborns; failure of antiviral agents to resolve infections or precise mechanism whereby HBV causes hepatocellular carcinoma (HCC). Based on the increased numbers of hepatic stem/progenitor cells (HPCs) present within the neonatal liver, the refractoriness of these cells to the effects of interferons and xenobiotics and their ability to undergo malignant transformation, we hypothesize that HBV infection of HPCs could explain these and perhaps other clinical features of chronic HBV. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the diagnostic value of anti-smooth muscle antibodies (ASMA) and two liver markers (gamma-glutamyl transpeptidase [GGT] and alkaline phosphatase [ALP]) for differentiating between patients with extrahepatic biliary atresia (EHBA) and idiopathic neonatal hepatitis (INH).Materials and Methods: During April 2010-2011, all infants at 2 weeks of age who were diagnosed with cholestasis and admitted to Children's Hospital of Tabriz were enrolled. Based on the results of physical examination, laboratory, imaging and pathological studies, neonates were divided into two groups (EHBA and INH). Receiver operating characteristics analysis was used to define sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for ASMA, GGT and ALP.Results: Thirty neonates with cholestasis (18 with EHBA and 12 with INH) and mean age of 54.66 ΁ 25.86 days were enrolled. Total and direct bilirubin, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and ASMA titres were highly not significant (P > 0.05) in patients with INH. GGT (P = 0.008) and ALP (P = 0.01) had statistically significant differences that were higher in patients with EHBA. The sensitivity, specificity, PPV and NPV, accuracy, LR+ and LR- of SMA in differentiating cases with BA were 66.7%, 75%, 80% 60%, 70%, 2.68 and 0.44, respectively. For GGT, the values were 88.9%, 66.7%, 80%, 80%, 79.1%, 3.08 and 0.31, respectively. Finally, for ALP, the values were 77.8%, 75%, 82.4%, 69.2%, 80%, 2.66 and 0.24, respectively.Conclusion: Our study showed that ASMA may be a useful biomarker for differentiation of EHBA from INH. Further studies with larger samples are recommended for confirming the results of this study. [ABSTRACT FROM AUTHOR]

The most common conditions causing cholestatic jaundice in infants are biliary atresia, neonatal hepatitis, and Alagille syndrome. In these disorders, the clinical presentation includes jaundice, pale stools, dark urine and hepatomegaly. Splenomegaly is not an early feature since it is due to portal hypertension, a later event. The finding of cholestatic jaundice and a large spleen usually raises the suspicion of Niemann-Pick type C disease (NP-C), a lysosomal storage disorder. We present and discuss here a case of an infant with liver disease and splenomegaly that were not ascribed to NP-C, but to Gaucher disease type 2. Liver biopsy, enzymatic studies and whole exome sequencing allowed to make the diagnosis. Although rare, Gaucher disease can cause neonatal hepatitis. A prompt recognition is advocated. [ABSTRACT FROM PUBLISHER]

Background: Perinatal exposure to hepatitis C virus (HCV) antigens during pregnancy may affect the developing immune system in the fetus. We aimed to study the perinatal transmission of HCV structural and non-structural antigens. Methods: Sera from 402 pregnant mothers were tested for anti-HCV antibody and HCV RNA. HCV antigens were determined in sera from 101 HCV-infected mothers and their cord blood. Results: In both serum and cord blood samples, HCV NS4 (non-structural 4) at 27 kDa, E1 (envelope 1) at 38 kDa and E2 (envelope 2) at 40 kDa were identified, purified and quantified using western blotting, electroelution and ELISA. Maternal sera and neonate cord blood samples had similar detection rates for NS4 (94.1%), E1 (90.1%) and E2 (90.1%). The mean maternal serum levels (optical density, OD) of HCV NS4 (0.87 ± 0.01), E1 (0.86 ± 0.01) and E2 (0.85 ± 0.01) did not differ significantly (p > 0.05) from those of neonatal cord blood (0.83 ± 0.01, 0.87 ± 0.01 and 0.85 ± 0.01, respectively). Also, strong correlations (p < 0.0001) were shown between sera and cord blood sample levels of HCV NS4, r = 0.77; E1, r = 0.76 and E2, r = 0.80. The vertical transmission of these antigens in vaginal delivery did not differ significantly (p > 0.05) from those in caesarean section. Conclusions: These findings indicate that vertical transmission of HCV NS4, E1 and E2 antigens was very high. Thus, exposure to these antigens may influence the developing immune responses to natural infection or future vaccination. [ABSTRACT FROM AUTHOR]

Aim: The differentiation between neonatal hepatitis (NH) and extrahepatic biliary atresia (EHBA) is not always possible despite all the currently available diagnostic modalities. In this study, an attempt has been made to evaluate the role of nitric oxide (NO) levels in the peripheral blood to differentiate between the two conditions, one requiring early surgical intervention (EHBA) and the other amenable to conservative medical management (NH). Patients and Methods: Twenty patients who presented to the pediatric surgical service, over a 2 years period, with features of neonatal cholestasis were enrolled in the study. The diagnostic workup included documentation of history and clinical examination, biochemical liver function tests, ultrasonography, hepatobiliary scintigraphy (HS), and magnetic resonance cholangio-pancreaticography (MRCP). These patients did not show excretion on HS and intrahepatic ducts on MRCP . Hence, they were subjected to mini-laparotomy and operative cholangiography (OC). The EHBA patients were treated with the Kasai's portoenterostomy procedure, and the extrahepatic ducts were flushed with normal saline in NH patients. All patients were evaluated preoperatively for levels of NO in the peripheral blood by the Greiss reaction spectrophotometrically at 540 nm. Normal values were determined from a cohort of controls. The median (range) levels of NO in patients with EHBA and NH were compared, and the statistical significance of the difference was calculated by applying the Wilcox Rank Sum test. A P = 0.05 was considered as significant. Results: Of the 20 patients enrolled in the study, 17 patients were treated for EHBA (Group I) and the remaining 3 patients had patent ducts on OC and were thus diagnosed as NH (Group II). The mean age of the patients in Groups I and II was comparable: 2.79 ± 0.75 and 2.67 ± 0.58 months, respectively (P = 0.866). The median NO levels were significantly elevated in each of the two groups as compared to the controls (5.6 µmol/l, range 1.26-11.34 µmol/l); when compared among themselves, the NO levels were significantly higher in Group I, 64.05 µmol/l (range 24.11-89.43 µmol/l), when compared with Group II, 41.72 µmol/l (range 23.53-45.63 µmol/l) (P = 0.022). Conclusion: The serum levels of NO were found to be significantly higher in patients with EHBA as compared to those with NH. Hence, this may be a useful biochemical marker for the preoperative differentiation of EHBA from NH. However, a larger study is required for establishing the validity of the statistical significance. [ABSTRACT FROM AUTHOR]

Background/Aims: The basic problem in diagnosis of neonatal cholestasis (NC) is to differentiate biliary atresia (BA) from other non-obstructive disorders. Because if bile flow cannot be provided by surgery, BA leads to cirrhosis and death within the first year of life. The aim of the present study is to determine histopathological features that may help to differentiate BA from neonatal hepatitis (NH). Material and Methods: This retrospective study was carried out on 105 liver biopsy specimens of 74 infants with NC who were diagnosed between 2003 and 2012. Results: The mean age was 76.5 ± 40.64 days. The most valuable biopsy findings for the discrimination between NH and BA, in decreasing order of importance, were ductular proliferation ( p < 0.001), cholestasis in neoductuli ( p < 0.001), fibrosis ( p = 0.002), and extramedullar hematopoiesis ( p = 0.02). While Kasai operations were performed in 19 cases, liver transplantation was performed in 10 cases. Survival rate among the death cases with BA was longer than the survival time of the death cases with NH ( p = 0.023). Currently more children live with a close to normal quality of life with portoenterostomy and/or liver transplantation. On the contrary, NH can be more fatal with associated disorders such as growth retardation, specific infections, respiratory distress, and metabolic or endocrine diseases. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to investigate if neonatal transfusions could underlie chronic hepatitis C in adults for whom the disease transmission route was previously unknown. Study Design and Methods Questionnaires were sent to 255 patients with chronic hepatitis C born in Sweden in 1960 to 1975. The medical records of 230 of the patients, of whom 98 (43%) had unknown transmission route, were studied regarding the occurrence of neonatal blood transfusions. The clinical, virologic, and histopathologic characteristics of those found to have received transfusions as neonates were also studied. Results Four of 230 (1.7%; 95% confidence interval, 0.5%-4.4%) patients with hepatitis C had received blood products as neonates. Three of them had reported unknown transmission route. One had cirrhosis, while two had mild histopathologic findings on liver biopsy. Three out of four patients in the transfused group, including the patient with liver cirrhosis, had undergone treatment for hepatitis C, all of them with a sustained viral response. Conclusion Previously unidentified neonatal blood transfusions explain only a small fraction of chronic hepatitis C cases with unknown transmission route. Individual patients infected early in life can develop progressive liver damage as young adults and may benefit from antiviral treatment. The finding suggests that efforts are needed to actively trace and test adults who have been subjected to neonatal blood product transfusion before 1992. [ABSTRACT FROM AUTHOR]

Background: Anti HCV is transferred from positive mother to her newborn. To prevent this transfer of anti HCV, many health care providers stop the mother from breast feeding and recommend the checking of the newborn for anti HCV. If found positive, they take it as a chronic infection and recommend treatment of the child as soon as possible. Prohibition from breast feeding not only pushes these neonates towards nutritional deficiencies but also make them prone to infections. The testing also stigmatizes the mother and her newborn for life. The literature proves that this antibody transfer is passive and clears in majority of cases without any residual disease. Mother to infant transfer of anti-HCV and its natural course in Pakistani population is not known. Objectives: To determine the frequency of anti-HCV positivity and its natural course in infants born to anti-HCV reactive mothers. Subjects and Methods: Anti-HCV reactive mothers were registered from gynecology department and labor room of Nishtar Hospital Multan from 07-10-2010 to 07-04-2011, using non probability purposive sampling. The ALT of mothers was also checked. The babies born to these mothers were checked for anti- HCV by ELISA and ALT at 0 day (at the time of birth) and then at 6, 12, 18 and 24 months using venous blood samples. Data was entered and analyzed using SPSS-11. Results: Out of 35 anti-HCV reactive mothers; only one had ALT above the upper limit of normal (> 40 IU/L). A total of 35 babies were born to these mothers, out of whom 34(97.1%) were reactive to anti-HCV at the time of birth and only one was non reactive. At 6 months 2 babies had expired and 3 were lost to follow up, leaving 30 babies. Out of these 30 babies 11 became non-reactive and 19 were still reactive for anti-HCV at 6months. At 12 months, all 19 anti-HCV reactive cases became non reactive, indicating passive transfer of antibodies from the mother to these neonates which they lost by 12 months. ALT of all babies except 3 was raised at 6 months (> 40 IU/L) which became normal during the subsequent visits. Conclusion: Almost all children born to anti-HCV positive mothers were reactive at the time of delivery but they all became non-reactive by the age of 12 months indicating passive transfer of anti HCV from the mother to the neonate. [ABSTRACT FROM AUTHOR]

Early detection is the most effective way to improve the clinical outcome of biliary atresia (BA). Emerging metabolomics provides a powerful platform for discovering novel biomarkers and biochemical pathways to improve early diagnosis. The aim of this study is to find the potential biomarkers to distinguish BA from neonatal hepatitis syndrome (NHS) by using a metabolomics method. We comprehensively analyzed the serum metabolites in a total of 124 blood samples from patients with BA or neonatal hepatitis syndrome (NHS) and from normal individuals using advanced metabolomic approaches, and found that the levels of glutarylcarnitine (C5DC) significantly increased in the BA group while the levels of threonine (Thr) significantly rose in the NHS group comparing with the other groups. The levels of glutamic acid (Glu) in the BA group were significantly elevated compared to those in the NHS group, but still lower than the hyperbilirubinemia and normal controls. The levels of propionyl carnitine (C3), isovaleryl carnitine (C5) and glutamine (Gln) were reduced in the BA group compared to those in the NHS group, but still higher than the hyperbilirubinemia and normal controls. This study demonstrates the possibility of metabolomics as non-invasive biomarkers for the early detection of BA and also provides new insight into pathophysiologic mechanisms for BA. [ABSTRACT FROM AUTHOR]

Hyper IgD syndrome (HIDS) is a rare metabolic autoinflammatory syndrome characterised by recurrent febrile episodes, accompanied by various inflammatory symptoms. We present a case of severe HIDS in a young girl, whose symptoms started in the neonatal period with hepatomegaly, hepatitis, thrombocytopenia, and conjugated hyperbilirubinemia. From the age of five months, the child had recurrent febrile episodes, stomatitis, adenitis, and persistent hepatomegaly. The diagnosis of HIDS was established when she was three years and eight months old. This case report suggests that HIDS should be included in the differential diagnosis of neonatal hepatitis and conjugated hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

Hepatobiliary scintigraphy is an important diagnostic modality for work-up of neonatal cholestasis. Therefore, our objective was to evaluate the literature regarding the accuracy of hepatobiliary scintigraphy in differentiating biliary atresia from non-biliary atresia causes of cholestasis (collectively called neonatal hepatitis). Our search included Medline, SCOPUS and Google Scholar. Only studies using Tc-99 m-labeled immunodiacetic acid (IDA) derivatives were included. Overall, 81 studies were included in the meta-analysis. Pooled sensitivity and specificity were 98.7% (range 98.1-99.2%) and 70.4% (range 68.5-72.2%), respectively. Factors that increased specificity included the use of radiotracers with high hepatic extraction, administration of hepatic-inducing drugs (such as phenobarbital), use of a calculated dose/kg and administration of a booster dose in cases of non-excretion of the tracer in the bowel. SPECT imaging and duodenal fluid sampling also had high specificity; however, they need further validation because of the low number of studies. Semiquantitative imaging methods do not seem to have any incremental value. We conclude that hepatobiliary scintigraphy using IDA derivatives can be very useful for diagnostic work-up of neonatal cholestasis. To improve the specificity, several measures can be followed regarding type and dose of the radiotracer and imaging protocols. Non-imaging methods seem to be promising and warrant further validation. [ABSTRACT FROM AUTHOR]

Abstract: Background: A significant percentage of Taiwanese neonatal HB immunization recipients have subsequently exhibited low anti-HB titers at non-protective or undetectable levels. Several mechanisms have been proposed to explain this phenomenon, including low vaccination responsiveness, deficient lymphocyte function, inappropriate antigen processing and presentation, and abnormal cytokine secretion. Methods: To determine genetic influences resulting in high anti-HB titers, we divided a study cohort of 183 individuals into an anti-HBs≥1000mIU/mL group and a 10–1000mIU/mL anti-HBs titer group. Chi-square tests were used to compare genotype and allelic frequencies between the two groups. Results: Data from univariate and multivariate regression analyses of cytokine and cytokine receptor gene variants indicate (a) increased potential of high anti-HB titers in the presence of the TT genotype of the IL-4 rs2243250 SNP (OR=3.19; p =0.012) and the AA genotype of the IL-4R rs1805010 SNP (OR=2.25; p =0.048), and (b) individuals carrying the TT genotype of the IL-4 rs2243250 SNP had anti-HB titers at levels that were almost twice as high as those in individuals carrying the CC genotype (478.8mIU/mL and 290.3mIU/mL, respectively; p =0.033). Conclusion: Genetic determinants, especially IL-4 and IL-4R, may contribute to high anti-HB titers in immune responses to HB vaccinations. [Copyright &y& Elsevier]

Aiad HAS, Kandil MAH, Samaka RM, Sultan MM, Badr MT, Nada GEM. The role of ck7, ki-67, cd34 and vimentin in the differentiation between biliary atresia and idiopathic neonatal hepatitis in egyptian cholestatic neonates. APMIS 2012; 120: 529-38. The differentiation between biliary atresia (BA) and idiopathic neonatal hepatitis (INH) is challenging with many histological overlaps especially in the first weeks of life. This study aimed to investigate the role of immunohistochemical staining of CK7, Ki67, CD34, and vimentin in addition to other clinicopathological features in the differentiation between BA and INH. Cases included 30 infants with BA and 30 infants with INH. The diagnosis was based on clinical, laboratory, and liver biopsy examination. Female gender and elevated serum gamma glutamyle transferase were in favor of BA. Portal tract changes, such as bile ductular proliferation documented by CK7, Ki67 immunostaining and angiogenesis documented by CD34 immunostaining, favored the diagnosis of BA. Copper associated protein was positive in 70% of BA cases, but not detected in INH cases. Parenchymatous changes, such as giant cell transformation and positive iron deposition and Kupffer cell proliferation documented by vimentin immunostaining, favored the diagnosis of INH.CK7, Ki67, CD34, and vimentin are helpful adjuvant immunostaining in the differentiation between BA and INH. [ABSTRACT FROM AUTHOR]

Background & Aims: The Z variant (Glu342Lys) of α1-antitrypsin (AT) polymerizes and accumulates in the hepatocyte endoplasmic reticulum (ER) predisposing to neonatal hepatitis and liver cirrhosis. The resultant secretory defect leaves the lungs vulnerable to elastolysis and early-onset emphysema. Our aim in this study was to evaluate the effect of targeting strand 4a (s4A) as a strategy to inhibit polymerization and restore plasma secretion. Methods: HEK293 cells and HepG2 cells were transfected with Z-AT (Z-AT cells) or control M-AT (M-AT cells). The effect of Ac-TTAI-NH2 (4M), Ac-FLEAIG-NH2 (6M), and Ac-SEAAASTAVVIA-NH2 (12M) on preventing and reversing intracellular Z-AT polymers and secretion of AT was evaluated by pulse-chase/immunoprecipitation, ELISA, and immunoblot with a polymer-specific antibody (ATZII). The ER overload response was assessed by RT-PCR for PERK, calnexin, and RGS16, and ELISA for NF-κB, IL-6, and IL-8. Results: All peptides prevented the intracellular accumulation of Z-AT (4M>6M>12M) in comparison with control peptides, with detection of the AT–Inhibitor complex in inclusion bodies. In so doing, 4M also significantly increased the concentration of secreted Z-AT and the elastase inhibitory activity. Furthermore, the 4M peptide was able to reverse the intracellular aggregation of Z-AT. The ER accumulation of Z-AT was shown to induce PERK-dependent NF-κB, IL-6, IL-8, and RGS16 and calnexin; all of which could be abrogated effectively by 4M. 4M had no effect on apoptosis or cell viability. Conclusions: These findings are the first evidence that targeting s4A can prevent the cellular accumulation and deleterious effects of Z-AT and restore its plasma concentrations. As such, this is a major step towards treatment of patients with Z-AT-related disease. [Copyright &y& Elsevier]

Ursodeoxycholic acid (UDCA) is a steroid bile acid approved for primary biliary cirrhosis (PBC). UDCA is reported to have "hepato-protective properties". Yet, UDCA has "unanticipated" toxicity, pronounced by more than double number of deaths, and eligibility for liver transplantation compared to the control group in 28 mg/kg/day in primary sclerosing cholangitis, necessitating trial halt in North America. UDCA is associated with increase in hepatocellular carcinoma in PBC especially when it fails to achieve biochemical response (10 and 15 years incidence of 9% and 20% respectively). "Unanticipated" UDCA toxicity includes hepatitis, pruritus, cholangitis, ascites, vanishing bile duct syndrome, liver cell failure, death, severe watery diarrhea, pneumonia, dysuria, immune-suppression, mutagenic effects and withdrawal syndrome upon sudden halt. UDCA inhibits DNA repair, co-enzyme A, cyclic AMP, p53, phagocytosis, and inhibits induction of nitric oxide synthatase. It is genotoxic, exerts aneugenic activity, and arrests apoptosis even after cellular phosphatidylserine externalization. UDCA toxicity is related to its interference with drug detoxification, being hydrophilic and anti-apoptotic, has a long half-life, has transcriptional mutational abilities, down-regulates cellular functions, has a very narrow difference between the recommended (13 mg/kg/day) and toxic dose (28 mg/kg/day), and it typically transforms into lithocholic acid that induces DNA strand breakage, it is uniquely co-mutagenic, and promotes cell transformation. UDCA beyond PBC is unjustified. [ABSTRACT FROM AUTHOR]

Abstract: Background: Maternal–infant transmission of hepatitis B virus (HBV) during birth carries a high risk of chronic HBV infection in infants. Appropriate neonatal prophylaxis is effective in preventing perinatal transmission of HBV. The purpose of this study was to evaluate the protective efficacy of anti-HBV sero-vaccination in newborns of HBsAg positive mothers from Mayotte, French island in the Mozambican canal. Patients and methods: One-hundred newborns of HBsAg positive mothers were identified retrospectively on the basis of hospital medical record and hepatitis B immune globulin (HBIG) prescriptions review from 1994 to 2007. To determine the rate of protective efficacy of neonatal prophylaxis defined by anti HBs antibodies >10IU/mL with negative HBsAg, anti HBc and HBV DNA testing, HBV serological markers were performed in vaccinated children. Results: Eighty-three of 100 newborns (83%) were given a complete sero-vaccination. Maternal HBe Ag status at delivery (available in 93%) was positive in 56 (60%) of cases and HBV viral load (available in 57%) was <5logIU/mL, between 5 and 7logsIU/mL and >7logsIU/mL in 23 (40.4%), 12 (21%) and 22 (38.6%), respectively. HBV markers in all children at a median age of 5years [IQR 2–8] showed that 76% were protected with anti HBs >10IU/mL, despite incomplete sero-vaccination in 12 infants; 6% of infants had anti-HBs and anti-HBc positivity with undetectable HBV DNA, 1% had isolated anti HBc while 14% were seronegative. Only 3% had evidence of immunoprophylaxis failure: 1 infant was HBsAg carrier and 2 had detectable HBV DNA without HBsAg (occult HBV infection). The only factor associated with sustained protective efficacy was on time serological control performed within one year of life, whereas maternal age, HBeAg status and HBV viral load on delivery were not. Conclusion: The anti–HBV sero-vaccination of newborns of HBsAg-positive mothers is fairly done in Mayotte and allows a high protection of mother-to-child transmission in a mean endemic area with fair safety. Screening of sero-vaccination failures has to be reinforced in order either to revaccinate or to treat infected children. [Copyright &y& Elsevier]

This case-series analyzed the outcome of live donor liver transplantation (LT) performed in children <7.5kg from January 2008 to June 2009 at our center. Five patients (3 males, 2 females, mean age, 8.2 ± .4 months; mean weight 6.8 ± 0.4 kg) underwent LT. The indications of LT included biliary atresia (3) and idiopathic neonatal hepatitis (2). Postoperative complications included acute rejection (1), portal venous thrombosis (1), bile leak (1), severe hypertension (1) and bacterial sepsis (4). There were no donor related complications. The median follow-up duration is 11 months with patient and graft survival rates of 100% each, respectively. [ABSTRACT FROM AUTHOR]

Several letters to the editor are presented in response to the articles in the previous issue of the Journal of Paediatrics and Child Health which includes the "Acute Colonic Pseudo-obstruction in Paediatric Oncology Patients" and "A Case of Neonatal Coxsackie B Virus Brainstem Encephalitis."

Background: Perinatal asphyxia is a major cause of neurologic morbidity and mortality. The purpose of this study was to investigate variations in nucleated red blood cell (NRBC) count per 100 white blood cells (WBC) and absolute NRBC/mm3 in blood associated with perinatal asphyxia and its relationship to both the severity and short term prognosis of asphyxia. Methods: A prospective (case-control) study was undertaken between October 2006 and December 2008, in the Neonatal Intensive Care Unit, Ghaem Hospital, Mashhad, Iran. A total of 91 infants completed the study. Levels of nucleated red blood cell per 100 white blood cells and absolute nucleated red blood cell counts in venous blood were compared for 42 asphyxiated (case group) and 49 normal neonates (control group). These parameters were also related to the severity of asphyxia and clinical outcome. Results: The NRBC/100 WBC and absolute nucleated red blood cell levels in the blood of newborns in the control group were 3.87±5.06 and 58.21±87.57/mm3, respectively; whereas the corresponding values in the cases were 18.63±16.63 and 634.04±1002/mm3, respectively (P<0.001). A statistically signi cant negative correlation existed between nucleated red blood cell level and indicators of the severity of perinatal asphyxia, first minute Apgar score and blood pH (P<0.001), respectively. A positive correlation was demonstrated between these parameters and severity of asphyxia, acidosis, and poor outcome (P<0.05). Conclusions: The NRBC/100 WBC and/or absolute nucleated red blood cell are simple markers for assessment of severity and early outcomes of perinatal asphyxia. [ABSTRACT FROM AUTHOR]

We report two cases of neonatal hepatitis with herpes simplex virus (HSV) infection. Whether the HSV infection was the cause of hepatitis, or merely associated with it is not clear. While, in the first case, resolution could not be achieved despite high-dose antiviral treatment with acyclovir and liver transplant had to be advised; in the second case, there was complete resolution of the disease without antiviral therapy. Role of acyclovir in these children needs further assessment. [ABSTRACT FROM AUTHOR]

Introduction: Early differentiation of biliary atresia from neonatal hepatitis is of utmost importance, since on time surgery of biliary atresia significantly improves the outcome. Hepatobiliary scintigraphy is an integral part of diagnosis work-up of these patients; however its specificity for diagnosis of biliary atresia is suboptimal. In this study we evaluated the value of ursodeoxycholic acid pre-treatment for improvement of hepatobiliary scintigraphy specificity. Methods: Thirty consecutive infants with direct heperbilirubinemia were included into the study. All infants underwent hepatobiliary scintigraphy with 99mTc-bromo iminodiacetic acid (99mTc-BRIDA) twice (first after pretreatment with phenobarbital and the other time after pre-treatment with ursodeoxycholic acid). Results: Of 30 patients included into our study 13 had final diagnosis of extrahepatic biliary atresia and 17 had neonatal hepatitis. Bowel was visualized in 11 patients with neonatal hepatitis after phenobarbital pre-treatment and in 16 after ursodeoxycholic acid pretreatment which amounts to 80 % and 96.6 % specificity for diagnosis of biliary atresia with phenobarbital and ursodeoxycholic acid respectively. All patients had complications of phenobarbital administration (lethargy, poor feeding, irritability, hypotonia, etc) to some extent. These findings decreased significantly after discontinuation of phenobarbital and were not present with ursodeoxycholic acid. Conclusion: Ursodeoxycholic acid is a safe and efficient drug for pre-treatment of patients with neonatal cholestasis syndrome who are going to undergo hepatobiliary scintigraphy. Compared to phenobarbital, this drug has fewer complications and is more efficient. [ABSTRACT FROM AUTHOR]

Objective:The purpose of this pilot trial was to determine whether rates of contact dermatitis following cutaneous antisepsis for central catheter placement were similar among neonates treated with chlorhexidine gluconate and povidone-iodine. Chlorhexidine gluconate absorption was also evaluated.Study Design:Infants weighing 1500 g and 7 days of age were randomized to a 10% povidone-iodine or 2% chlorhexidine gluconate site scrub before catheter placement. Primary outcomes evaluated included dermatitis, catheter colonization and chlorhexidine gluconate absorption.Result:A total of 48 neonates were enrolled. Colonization rates were similar among treatment groups (P<0.6). Dermatitis did not occur at chlorhexidine gluconate (central catheters, n=24; peripheral catheters, n=29) sites. Seven neonates had measurable chlorhexidine gluconate concentrations (range 13 to 100 ng ml−1) during catheterization.Conclusion:In this small trial chlorhexidine gluconate antisepsis was tolerated by study neonates. Chlorhexidine gluconate was cutaneously absorbed. Larger trials are needed to determine efficacy and tolerance of chlorhexidine gluconate in neonates. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To retrospectively analyze different methods in differentiating biliary atresia from idiopathic neonatal hepatitis. Methods: Sixty-nine infants with cholestatic jaundice and final diagnosis of idiopathic neonatal hepatitis (INH) and biliary atresia (BA) were studied retroprospectively from January 2004 to December 2006. A thorough history and physical examination were undertaken. All cases underwent abdominal magnetic resonance cholangiography (MRCP), ultrasonography (US), hepatobiliary scintigraphy (HBS), HBS single-photon emission computer tomography (HBS SPECT), and operation or percutaneous liver biopsy. The accuracy, sensitivity, specificity, and predictive values of these various methods were compared. Results: There were 39 girls and 30 boys, among whom 35 had INH (age, 61±17 days) and 34 had BA (age, 64±18 days). The mean age at onset of jaundice was significantly lower in cases of BA when compared to INH cases (9±13 vs. 20±21 days; P=.032). The diagnostic accuracy of different methods was as follows: liver biopsy, 97.1%; HBS SPECT, 91.30%; MRCP, 71.01%; HBS, 66.67%; US, 65.22%. Conclusion: Our results indicate that biopsy of the liver is considered as the most reliable method to differentiate INH from BA. The accuracy of HBS SPECT is higher than that of MRCP, HBS, and US. There was no significant difference in diagnostic accuracy among MRCP, HBS, and US. [Copyright &y& Elsevier]

The advent of liver transplantation for end-stage liver disease (ESLD) in children has necessitated a major rethink in the preoperative preparation and management from simple palliative care to active directed intervention. This is particularly evident in the approach to the nutritional care of these patients with the historical understanding of the nutritional pertubations in ESLD being described from a single pediatric liver transplant center. ESLD in children is a hypermetabolic process adversely affecting nutritional status, metabolic, and non-metabolic body compartments. There is a complex dynamic process affecting metabolic activity within the metabolically active body cell mass, as well as lipid oxidation during fasting and at rest, with other factors operating in conjunction with daily activities. We have proposed that immediately ingested nutrients are a more important source of energy in patients with ESLD than in healthy children, among whom energy may be stored in various body compartments. [ABSTRACT FROM AUTHOR]

We retrospectively reviewed the role of ursodeoxycholic acid in infants having nonsurgical cholestasis attending the Hepatology Clinic, New Children Hospital, Cairo University, Egypt, from 1985 until 2005. Files of 496 infants with neonatal hepatitis and 97 with intrahepatic bile duct paucity were included; of them 241 (48.6%) and 52 (46.4%) received 20-40 mg/kg/day ursodeoxycholic acid for 319.2 +/- 506.9 days and 480.3 +/- 583.3 days, respectively. The outcome of infants with neonatal hepatitis with intake of ursodeoxycholic acid and those without was: 108 (44.8%) and 179 (70.2%) successful (P = 0.000), 11 (4.6%) and 13 (5.1%) improved (P = 0. 474), 112 (46.5%) and 61 (23.9%) suffered failed outcome (P = 0.000), and 10 (4.1%) and 2 (0.78%) died (P = 0.014), respectively. Likelihood of successful outcome with ursodeoxycholic acid intake was 0.345 (P = 0.000), and that of deterioration was 2.76 (P = 0.000). For those having intrahepatic bile duct paucity likelihood of successful outcome with ursodeoxycholic acid intake was 0.418 (P = 0.040) and that of deterioration was 2.64 (P = 0.028). Ursodeoxycholic acid failed in management of this cohort of infants with nonsurgical cholestasis. [ABSTRACT FROM AUTHOR]

Aim: To study the accuracy of various clinical and investigational parameters to differentiate biliary atresia (BA) from neonatal hepatitis (NH). Methods: It was a prospective study, conducted in a tertiary care hospital. A total 101 infants with neonatal cholestasis (NCS) were included in this study. Following a baseline hepatobiliary scintigraphic study (HBS), it was repeated after giving UDCA (40 mg/kg/day for 48–72 h). The sensitivity and specificity of clinical and investigational parameters were calculated with peroperative cholangiogram as gold standard. Results: The mean age was 2.8 ± 1.7 months and 82 were male. Of these, 35 were diagnosed to have BA and 66 had NH (idiopathic 25, sepsis/UTI 20, galactosaemia 11, TORCH 2 and others 8). Persistently clay stool was found to have modest accuracy (79%) and the accuracy of HBS improved significantly following UDCA therapy (91% from 77%, p < 0.01) whereas liver biopsy was 100% accurate in differentiating BA from NH. The outcome of BA cases with ductal plate malformation (DPM) was worse. Conclusion: One-third of all NCS in India is due to BA and among the intrahepatic causes acquired infection and galactosaemia are common. Liver biopsy is the best method to differentiate NH from BA. [ABSTRACT FROM AUTHOR]

The term cholestasis is Greek in origin, meaning bile stoppage. In its most overt form, cholestasis presents to the clinician as jaundice. However, jaundice is only the tip of the iceberg of cholestatic liver disease. The incidence of neonatal cholestasis is estimated around 1 in 2500 live births. Cholestasis must always be considered in newborns with prolonged jaundice lasting more than 14-21 days. There are a number of contributing factors for neonatal cholestasis which include bile duct abnormalities; infections, such as sepsis and urinary tract infections; inherited and metabolic disorders; endocrine disorders; chromosomal disorders; toxicity from parenteral nutrition; vascular disorders; prematurity, lack of enteral feedings and medications. The most common causes of neonatal cholestasis are biliary atresia and idiopathic neonatal hepatitis. [ABSTRACT FROM AUTHOR]

Surgery in infants and young children with haemophilia, when preceded by accurate diagnosis and accompanied by safe and effective factor prophylaxis, is not associated with a significant risk of haemorrhage. Haemophilic newborns undergoing circumcision or major surgery prior to diagnosis and in the absence of appropriate haemostatic prophylaxis remain as a concern. Inhibitor development has replaced haemorrhage as the major surgical complication in the developed world, largely because of the intensity of treatment used to secure haemostasis. For that reason only, essential surgery should be performed. Intracranial haemorrhage (ICH) during the neonatal period affects 3.5–4.0% of all haemophilia boys in countries with a good standard of health care, which is considerably (40–80 times) higher than expected in the normal population. Because of the high frequency of sporadic cases, ICH in the neonatal period can only be partially prevented by improved carrier diagnosis and counselling. Infections and thrombosis are the major serious complications of central venous lines. Large differences are seen in the frequency of these complications, the most plausible explanations are probably related to the protocol used for device care, the quality of education and the compliance of the users, an issue addressed in an on-going study. [ABSTRACT FROM AUTHOR]

The article focuses on the effects of neonatal and fetal viral infections on the child growth and the possible diseases from viral infections. It explores the pathogenesis, outcomes, and the diseases related to viral and parasitic infections in perinatal. It states that viral infections in neonatal occur in one or more perinatal periods including in utero, intrapartum, and early or late postpartums. It mentions that the systems of the perinatal viral and parasitic infections differ according to the disease though it all starts in maternal infection. It explores several inborn viral infections and diseases including hepatitis B., HIV, and human papillomavirus.