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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

Cholate-CoA ligase (CCL) and bile acid-CoA: amino acid N-acyltransferase (BAAT) sequentially mediate bile-acid amidation. Defects can cause intrahepatic cholestasis. Distinction has required gene sequencing. We assessed potential clinical utility of immunostaining of liver for CCL and BAAT. Using commercially available antibodies against BAAT and CCL, we immunostained liver from an infant with jaundice, deficiency of amidated bile acids, and transcription-terminating mutation in BAAT. CCL was normally expressed. BAAT expression was not detected. Immunostaining may facilitate diagnosis in bile-acid amidation defects.

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.

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]

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.

BACKGROUND: Biliary atresia is not suitable as a method for early diagnosis because it mainly depends on intraoperative diagnosis, and the operation is complicated, and there is a great injury to the child. Therefore, finding simple and effective blood biochemical diagnostic indicators will improve early diagnosis efficiency.OBJECTIVE: To measure the plasma alpha-fetoprotein level in children with biliary atresia and to investigate the application value of plasma alpha-fetoprotein level and blood biochemical indicators.METHODS: Blood samples were harvested from 48 infants with biliary atresia, 20 infants with neonatal hepatitis, and 9 healthy controls.Plasma alpha-fetoprotein level was measured by enzyme-linked immunosorbent assay. The correlation between plasma alpha-fetoprotein level and blood biochemical indicators was analyzed to establish a potential diagnosis model. This study was approved by the Ethics Committee of Xinhua Hospital, China(approval No. XHEC-D-2013-026).RESULTS AND CONCLUSION: Plasma alpha-fetoprotein level in infants with biliary atresia and neonatal hepatitis was significantly higher than that in the healthy controls(P < 0.001), but no significant difference in plasma alpha-fetoprotein level was observed between infants with biliary atresia and neonatal hepatitis(P > 0.05). There was no significant difference in plasma alpha-fetoprotein level between infants with different stages of cirrhosis(P > 0.05). Blood biochemical indexes indicated severe liver injury in infants with biliary atresia and neonatal hepatitis. There were significant differences in plasma prealbumin(P < 0.05) and γ-glutaminyl transpeptidase levels between infants with biliary atresia and neonatal hepatitis(P < 0.01). Plasma alpha-fetoprotein level was negatively correlated with γ-glutaminyl transpeptidase level(r =-0.516, P < 0.01). A potential diagnosis model was established based on plasma alpha-fetoprotein, prealbumin,γ-glutaminyl transpeptidase levels, age and sex of infant patients, with a sensitivity of 81.82%, specificity of 91.67%, and area under the curve of 0.939. Results suggest that plasma alpha-fetoprotein level increased in infants with biliary atresia. Establishing a diagnosis model based on blood biochemical indicators such as plasma alpha-fetoprotein is of certain reference value for clinical diagnosis of biliary atresia. [ABSTRACT FROM AUTHOR]

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]

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.

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.

Objection: The aim of the present is to retrospectively analyze children with the diagnosis of neonatal cholestasis in terms of etiology, diagnostic methods, laboratuvary findings as well as treatment modalities and long-term results. Material and Method: Patients who had cholestasis in first three months of life were included in this study. Patients were grouped as intrahepatic and extrahepatic cholestasis. Biliary atresia, inspissated bile syndrome and choledochal cysts were investigated in the intrahepatic cholestasis group. Patients were evaluated retrospectively in terms of their diagnosis, complaints, clinical courses, laborauary findings, responses to treatment and prognosis. Results: Study group of 105 patients consisted of 43 female (41%), 62 male (59%) patients. Forty-six (43%) patients had a history of premature delivery (n=46: 43%) including those who were born between 30th-37th (n=36: 34.3%) or before 30th (n=10: 9.3%) gestational week while 39 patients were low birth- weight infants. Intrahepatic, and extrahepatic cholestasis were detected in 81%, and 19% of the patients. Among a total of 31 patients, acholic stools were detected in 18 (90%) patients with extrahepatic , and in 13 (15.3%) patients with intrahepatic cholestasis. Birth weights were lower in patients with intrahepatic cholestasis relative to those with extrahepatic cholestasis. During the follow-up period, 38 (44.7%) patients with intrahepatic and 7 (35%) patients with extrahepatic cholestasis had recovered. Conclusion: Results of the present study have indicated a significant delay in the diagnosis of neonatal cholestasis. This delay can cause a decrease in the chance of early surgery in cases of biliary atresia. Differently from the literature, ultrasonographic examination showed no triangular cord sign in any patients which suggested dearth of education and experience on this topic. Futhermore, overlooking an increase in gama glutamil transferaz (GGT), the presence of splenomegaly, birth weight, and acholic stools which may be significant findings for hepatic disease indicates the necessity to increase awareness of pediatric physicians. [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]

We have performed primary examination of 50 children with neonatal hepatitis. Prevalence of herpes infection as the etiologic agent (40,0%) has been found, as well as parenteral hepatitis, both as an isolated (26,0%) and mixed infections. We conducted a comparative analysis of clinical and laboratory data at initial examination and determined the outcomes of neonatal hepatitis to 12 months of life depending on the etiology. Congenital CMV- etiology hepatitis characterized by more cytolysis, mainly due to aspartate aminotransferase and cholestasis, which is 33,3% of cases combined by acholia and urobiliya. In 50,0% of patients with CMV-hepatitis was detected fibrosis with a mean value of liver elastography 9,9 kPa, which is ІІІ degrees of fibrosis METAVIR scale, whereas in children with primary chronic hepatitis C and concomitant HCV + DNA-virus infection fibrosis was not registered. Despite on the large number of modern non-invasive techniques for determining the degree of hepatic fibrosis, the use of its in children during the first months of life is limited and does not allow to predict disease outcome.

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]

α1-Antitrypsin (α1-AT) belongs to serine protease inhibitor (Serpin) superfamily and is the main protease inhibitor in human circulation. It can inhibit many proteases to protect tissues from digradation. The mutant Z (Glu342Lys) of α1-AT predisposes to the early onset of emphysema due to decreased functional α1-AT in the lung and to neonatal hepatitis due to accumulation of α1-AT polymers in the endoplasmic reticulum of hepatocytes, which disrupts the balance between protease and protease inhibitors. This paper reviews recent research progress on the pathogenic mechanism and the prognosis of α1-antitrypsin deficiency. [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]

Idiopathic neonatal hepatitis (INH) is a term used to describe prolonged neonatal intrahepatic cholestasis in the first six months of life, whose histopathological lesion is characterized by the presence of "giant cells", in the absence of other causes of type Infectious, genetic or obstructive. The frequency of INH is about 15% of cases of neonatal cholestasis. Idiopathic neonatal hepatitis is a diagnosis of exclusion in children with prolonged cholestasis. The decrease in its prevalence is due to advances in the biochemical and genetic diagnosis of hereditary and metabolic diseases that occur during early childhood. The role of biopsy in the diagnosis of neonatal hepatitis needs to be redefined to take advantage of the progress that has been made in genetic and immunohistochemical studies in the search for other causes of this entity. Medical management is supportive to optimize growth and development, as well as treating complications in case of a chronic liver disease. [ABSTRACT FROM AUTHOR]

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.

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]

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]