Cause Of Cholestatic Jaundice Research Articles

The Liver and Lysosomal Storage Diseases: From Pathophysiology to Clinical Presentation, Diagnostics, and Treatment.

The liver, given its role as the central metabolic organ, is involved in many inherited metabolic disorders, including lysosomal storage diseases (LSDs). The aim of this manuscript was to provide a comprehensive overview on liver involvement in LSDs, focusing on clinical manifestation and its pathomechanisms. Gaucher disease, acid sphingomyelinase deficiency, and lysosomal acid lipase deficiency were thoroughly reviewed, with hepatic manifestation being a dominant clinical phenotype. The natural history of liver disease in the above-mentioned lysosomal disorders was delineated. The importance of Niemann-Pick type C disease as a cause of cholestatic jaundice, preceding neurological manifestation, was also highlighted. Diagnostic methods and current therapeutic management of LSDs were also discussed in the context of liver involvement.

Spontaneous Rupture of Choledochal Cyst: A Rare Presentation

AbstractCholedochal cyst (CDC) is a rare surgical cause of cholestatic jaundice in infants. Spontaneous rupture is an unusual presentation of a previously undiagnosed CDC and is also a rare cause of biliary peritonitis in children. Here, we report a case of a 1-year-old boy who was evaluated for progressive abdominal distension. Ultrasonogram showed gross ascites with echogenic particles, dilated common bile duct (CBD), common hepatic duct (CHD), and upstream intra hepatic biliary radicle dilatation (IHBRD). CECT sections of the abdomen showed gross ascites and IHBRD with disproportionate dilatation of CHD and CBD. At laparotomy, a type 1 CDC with rupture of the anterior wall was found. The cyst was excised followed by hepaticojejunostomy. In a sick child with abdominal pain, cholestatic jaundice and biliary ascites, a high index of suspicion during imaging will help in the correct diagnosis and surgery for a potentially fatal ruptured CDC.

Ultrasound elastography in the diagnosis of biliary atresia in pediatric surgery: a systematic review and meta-analysis of diagnostic test

BackgroundBiliary atresia (BA) is one of the most fatal hepatobiliary diseases in infants and young children, and is easy to cause obstructive jaundice in infants and children, and liver transplantation in children. BA and infantile hepatitis syndrome are the main causes of cholestatic jaundice. The early clinical manifestations are extremely similar, and timely identification is difficult. Therefore, early and differential diagnosis of BA is crucial. At present, there are many imaging diagnosis methods for BA, such as ultrasound examination and nuclear magnetic resonance. Ultrasound elastography (USE) is the most popular method. However, the application of USE in BA is still in the exploratory stage.MethodsPubMed, Web of Science, Embase, Cochrane Library, and other databases were searched for articles on USE diagnosis of pediatric surgical BA. Later, the articles were screened, and the included articles should meet the following requirements: the research objects were children with BA; the intervention measures were USE diagnosis; the control group was diagnosed by other methods than USE. RevMan5.3 was adopted for quality assessment, and forest maps and summary receiver operating characteristic (SROC) curves were constructed.ResultsFinally, seven articles covering 490 patients were included. There were 120 patients in the control group. The included articles showed good quality and there was no obvious bias. The area under the SROC curve (AUC) for USE diagnosis of BA was 0.93, the sensitivity was 0.93 (95% CI: 0.72–1.00), and the specificity was 0.95 (95% CI: 0.74–1.00).DiscussionUSE showed high diagnostic value for pediatric surgical biliary tract closure.

A model incorporating serum C3 complement levels may be useful for diagnosing biliary atresia in infants

IntroductionCorrectly identifying patients with biliary atresia (BA), while avoiding invasive diagnostic methods is challenging. The purpose of this study was to determine the value of serum immune indicators for distinguishing BA from other causes of cholestasis in infants. Patients and methodsThe data of infants with a surgical/histological diagnosis of BA and those with other causes of cholestatic jaundice were retrospectively analyzed. Patients were divided into a BA group and a cholestasis control (CC) group. Biochemical parameters, major lymphocyte subsets, immunoglobin and C3 and C4 complement levels were compared between the groups. ResultsA total of 129 infants with BA and 63 with other causes of cholestasis (CC control group) with a median age of 2.2 months were included in the analysis. The levels of CD3+ T cells, CD3+CD4+ T cells, and premature T cells and the levels of C3 and C4 were all significantly higher in the BA group compared to the CC group (all P<0.05). Pair-wise correlation analyses indicated that C3 and C4 had a significant positive correlation with γ-GT in the BA group, but not in the CC group. Five indices were found to be significantly associated with BA: stool color, globulin, γ-GT, C3 and C4. A model incorporating stool color, gamma-glutamyl transpeptidase level, and C3 level exhibited an area under the ROC curve (AUC) of 0.93, and a sensitivity of 93% and specificity of 83% for the diagnosis of BA. ConclusionsModels incorporating serum C3 levels may be useful for accurately diagnosing BA in infants.

Improving Poor Outcomes of Children With Biliary Atresia in South Africa by Early Referral to Centralized Units

Objectives: Biliary atresia (BA) is a progressive fibrosing cholangiopathy of infancy, the most common cause of cholestatic jaundice in infants and the top indication for liver transplantation in children. Kasai portoenterostomy (KPE) when successful may delay the requirement for liver transplantation, which in the majority offers the only cure. Good outcomes demand early surgical intervention, appropriate management of liver cirrhosis, and in most cases, liver transplantation. These parameters were audited of children with BA treated at the Steve Biko Academic Hospital (SBAH) in Pretoria, South Africa. Methods: All children with BA who were managed at SBAH between June 2007 and July 2018 were included. Parameters measured centered on patient demographics, timing of referral and surgical intervention, immediate and long-term outcomes of surgery, and follow-up management. Results: Of 104 children treated, 94 (90%) were KPE naive. Only 23/86 (26%) of children were referred before 60 days of life and 42/86 (49%) after 120 days. Median time to surgical assessment and surgery was 4 (IQR 1–70) and 5 (IQR 1–27) days post presentation, respectively. The median age at KPE was 91 days (IQR 28–165), with only 4/41 (12%) of KPEs performed before 60 days of life. Of those with recorded outcomes, 12/33 (36%) achieved resolution of jaundice. Only a third of the cohort were referred for transplantation. Conclusion: Children with BA have poor outcomes in the public health sector in South Africa. Late referrals, delayed diagnostics, advanced age at KPE with low drainage rates, poor follow–up, and low transplant rates account for low survival. Early referral to units offering expert intervention at all stages of care, including transplantation, would offer the best outcomes.

Evaluation of noninvasive methods for diagnosis of cholestasis in infancy

Background Cholestatic liver disease constitutes a large percentage of chronic liver diseases during infancy. Cholestasis is defined as interference with bile formation or flow owing to pathology anywhere between the hepatocyte and the ampulla of Vater. Aim To evaluate the different modalities used for diagnosing cholestasis in infants in Damanhour Medical National Institute (DMNI) to find out the sensitivity and the predictive values of each modality in defining the cause of cholestatic jaundice, whether surgical or medical. Patients and methods This study was a retrospective one which included 153 infants who were referred with cholestasis in first year of life to the Pediatric Hepatology Clinic of the Children's Department (DMNI) from June 2013 to December 2018. The medical records of the 153 infants with confirmed cholestasis were reviewed regarding the history and clinical examination, laboratory data, ultrasound, and liver biopsy. The cases were classified into two groups according to the etiology. Group I comprised (Extrahepatic Biliary Atresia) EHBA, and there were 40 patients in this group. Group II comprised non-EHBA (the medical causes of cholestasis), and there were 113 patients in this group. Results Nearly half (52%) of the patients were females. There were no significant differences regarding sex between EHAB and non-EHBA patients. An enlarged liver was also a common finding, being present in more than 66% of infants, irrespective of the underlying cause. Splenomegaly was more commonly noted in group II (27.43%) versus group I (12.5%), but the differences were not statistically significant. Persistently day stools were observed by 95% of mothers of babies of group I compared with 15% in group II, with a highly significant statistical difference. No significant differences were found between group I and group II regarding most tests of the biochemical profile, except Gamma-glutamyl transferase (GGT) and alkaline phosphatase (AL Ph), as they were significantly higher in group I compared with group II. However, aspartate transaminase (AST), alanine transaminase (ALT), and partial thromboplastin time were significantly higher in group II compared with group I. Conclusion and recommendations It is recommended the use of the developed model, GGT, and AL Ph as first line of investigations, and follow-up for excluding EHBA. Urgent referral of patients to perform a liver biopsy should be done based on the calculated probability of the developed model more than 0.128, GGT more than 500, and Al Ph more than 600. Campaigns to increase awareness among parents and primary care doctors are recommended for early drug and management.

S2582 Acute Hepatitis Secondary to Asymptomatic Epstein-Barr Virus (EBV) Infection

INTRODUCTION: Symptomatic EBV infection usually presents with fever, sore throat, lymphadenopathy, termed as infectious mononucleosis syndrome. Marginal elevation of liver enzymes may be seen however, acute symptomatic hepatitis without mononucleosis syndrome is rare. We present a case of a female with acute cholestatic hepatitis with laboratory-confirmed EBV infection without mononucleosis syndrome. CASE DESCRIPTION/METHODS: A 36-year-old female, underweight, with past history of alcohol use (sober for 60+ days), seizure disorder, sub-clinical hypothyroidism presented with intermittent nausea followed by non-bloody, non-bilious vomiting for 5 days without melena or blood in the stool. She didn’t report any fever, chills, night sweats, sick contacts, recent travel history. On clinical exam, her vital signs were blood pressure 112/78 mm Hg, pulse 104/min, oral temperature of 36.7 deg C and breathing comfortably on room air. Inspection notable scleral icterus without periorbital skin involvement, no buccal mucosa changes, enlarged tonsil, no spider nevi, or scratch mark on inspection, no lymphadenopathy on palpation. The abdomen was soft and protuberant on the exam with liver just palpable below costal margin but non-tender to palpation. Her home medicine includes oral vitamin B12, folic acid, zonisamide (no changes to regimen in 2 years). Initial laboratory evaluation revealed a normal white cell count with an elevated liver enzymes, bilirubin, and alkaline phosphatase (R factor: 1.2). An ultrasonography of abdomen showed a common bile duct diameter of 3 mm without any dilation of extra or intrahepatic ducts, visualized portion of the portal vein was patent and showed hepatopetal flow. Unremarkable pancreas with cholelithiasis without cholecystitis. To rule in/out additional causes of cholestatic jaundice, viral, and antibody panel were sent which were positive for EBV infection. Additionally, ANA was positive reflecting cross-reactivity between EBV proteins and autoantigens. Her symptoms improved with conservative management which included hydration and low-fat diet. DISCUSSION: EBV is an important cause of cholestatic hepatitis resulting in elevated liver enzymes and bilirubin, however, the presentation is usually associated with mononucleosis syndrome. EBV hepatitis as a differential in patients with cholestatic hepatitis but without demonstrable biliary obstruction, prompt identification would avoid costly and/or invasive diagnostic procedures. No effective treatment is available for EBV hepatitis.Table 1.: Laboratory profile on admission and 8 weeks later

Single Procedure Saline Lavage for Treatment of Inspissated Bile

Inspissated bile syndrome is a rare cause of cholestatic jaundice in infancy, occurring due to obstruction of the biliary ducts and gallbladder by biliary sludge. Traditional methods of treatment include surgical drainage or cholecystostomy drain placement. Both can be associated with complications and prolonged admission. We present 2 cases treated with a single percutaneous needle puncture of the gallbladder followed by saline lavage. Two neonates presented with cholestatic jaundice and sonographic evidence of biliary sludge and dilation of the common bile duct. Single sonographic-guided needle puncture of the gallbladder was followed by irrigation with saline. Clearing of the biliary sludge was confirmed by sonography and cholecystocholangiography. There was resolution of the cholestatic jaundice, with no complications or repeat procedures.

Identification of a novel splicing mutation in the SLC25A13 gene from a patient with NICCD: a case report

BackgroundNeonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive disorder and one of the most common inherent causes of cholestatic jaundice in Asian infants. Mutations in the SLC25A13 gene, which encodes citrin protein expressed in the liver, have been identified as the genetic cause for NICCD.Case presentationHere, we report a 4-month-old female with clinical features including jaundice, hyperbilirubinemia, hyperlactacidemia, and abnormal liver function. The patient was diagnosed with NICCD by differential diagnosis using genetic analysis. Mutations in 60 jaundice-related genes were tested by using amplicon sequencing, which was performed on an Ion S5XL genetic analyzer. A compound heterozygous mutation in the SLC25A13 gene was identified, consisting of a known deletion SLC25A13:c.852_855delTATG and a novel splicing mutation SLC25A13:c.1841 + 3_1841 + 4delAA. Sanger sequencing for the proband and her parents was performed to validate the result and reveal the source of mutations.ConclusionA compound heterozygous mutation in the SLC25A13 gene was identified in a 4-month-old female patient with NICCD. Our data suggest that amplicon sequencing is a helpful tool for the differential diagnosis of inherited diseases with similar symptoms. Further studies of the mutation spectrum of neonatal jaundice in China are warranted.

Primary Amyloidosis Presenting as Hepatomegaly in a Patient With Undiagnosed Multiple Myeloma: A Challenging Case of Pneumococcal Meningitis and Hepatomegaly With Obstructive Jaundice

Inflammation secondary to sepsis can involve multiple organs, including liver. Hepatocellular injury in sepsis results from hypoperfusion and inflammatory cytokines, manifesting as elevated alkaline phosphatase, AST, ALT and bilirubin. However right upper quadrant scans should be performed when in doubt to rule out other life threatening pathologies. We report a case of undiagnosed multiple myeloma and primary amyloidosis with liver and pancreatic involvement, admitted for sepsis secondary to meningitis. A 65-year-old male was brought to hospital after wife found him confused, diaphoretic and nonverbal. He was febrile and somnolent. Lumbar puncture confirmed bacterial meningitis for which he was treated, but later developed jaundice. His liver function tests were consistent with cholestasis. Right upper quadrant (RUQ) ultrasonography (images 1,2) and CT abdomen (image 3) did not show any tumors, stones or strictures but demonstrated massive hepatomegaly. Malignancy work-up was initiated for hypercalcemia, as PTH, PTHrP and vitamin D levels were normal. Serum protein electrophoresis (SPEP) showed abnormal band suggestive of a paraprotein in gamma region (1.00 g/dL), along with elevation of free Kappa and lambda light chains. Bone marrow biopsy revealed 10% plasma cells. Alkaline phosphatase, AST, ALT, and bilirubin, continue to trend up, peaking at 1521 U/L, 138 U/L, 129 U/L and 4.1 mg/dL (2.9 mg/dL- direct bilirubin) respectively. GGT was elevated at 1364 U/L and CA 19-9 at 3386 U/L. MCRP was negative for biliary or pancreatic duct dilatation. Liver biopsy confirmed primary amyloidosis. Hence patient was started on chemotherapy for IgG kappa multiple myeloma and primary amyloidosis, and had significant improvement in liver function tests and CA 19-9 after first cycle. Amyloidosis is a process of extracellular insoluble protein deposition that commonly involves gastrointestinal tract, with up to 90 percent liver involvement. Jaundice along with elevated alkaline phosphatase and transaminases is seen frequently with liver involvement but jaundice is associated with poor prognosis. Liver alone is almost never the sole organ affected, and in the above-reported case, later on biopsy of the pancreas was also consistent with widespread amyloid deposits. Even though amyloidosis represents a rare cause of cholestatic jaundice, it is important to consider it in differentials due to high mortality with median one-year survival of fifty percent in untreated cases.Figure: Right upper quadrant ultrasound - hepatomegaly.Figure: RUQ ultrasound showing normal CBD.Figure: CT abdomen - hepatomegaly.

Alagille syndrome in an eleven year old Nigerian child – A case report

Background: Alagille syndrome (AGS) is a rare cause of prolonged jaundice. It has an autosomal dominant inheritance pattern expressed variably, with a reported incidence of 1:100,000 live births in the United States. The objective is to highlight the clinical features and diagnostic challenges to this rare cause of cholestatic jaundice. Case Report: T.O, Female 11 years, had a history of recurrent episodes of yellowness of the eyes, first noticed soon after birth, associated with pale stools, dark urine, and body itching. From age three she was noticed to have progressive loss of sight, recurrent body swellings and irrational talks. She was diagnosed to have a cardiac murmur at age six, when diagnosis of ALS was made due to features of, recurrent jaundice and perculiar facies of broad forehead, flat nasal bridge, prognathia and genetic report of no mutation in JAG 1 gene, karyotype 46XX. At the time of current hospital admission she was in addition small for age, had hepatosplenomegy, ascities and talked irrationally. Chest radiograph showed multiple butterfly vertebrae; Echocardiograph aortic and pulmonary stenosis; Liver aminotransferase were marked elevated. Brain MRI showed multiple chronic infarcts. She was diagnosed with Allagille syndrome presenting in hepatic failure with encephalopathy. Conclusion: Allagille syndrome should be considered early in older children with persistent cholestatic jaundice. Keywords: Allagille, syndrome, cholestatic, jaundice, hepatic encephalopathy and congenital heart disease

Guideline for the Evaluation of Cholestatic Jaundice in Infants: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Cholestatic jaundice in infancy affects approximately 1 in every 2500 term infants and is infrequently recognized by primary providers in the setting of physiologic jaundice. Cholestatic jaundice is always pathologic and indicates hepatobiliary dysfunction. Early detection by the primary care physician and timely referrals to the pediatric gastroenterologist/hepatologist are important contributors to optimal treatment and prognosis. The most common causes of cholestatic jaundice in the first months of life are biliary atresia (25%-40%) followed by an expanding list of monogenic disorders (25%), along with many unknown or multifactorial (eg, parenteral nutrition-related) causes, each of which may have time-sensitive and distinct treatment plans. Thus, these guidelines can have an essential role for the evaluation of neonatal cholestasis to optimize care. The recommendations from this clinical practice guideline are based upon review and analysis of published literature and the combined experience of the authors. The committee recommends that any infant noted to be jaundiced after 2 weeks of age be evaluated for cholestasis with measurement of total and direct serum bilirubin, and that an elevated serum direct bilirubin level (direct bilirubin levels >1.0 mg/dL or >17 μmol/L) warrants timely consideration for evaluation and referral to a pediatric gastroenterologist or hepatologist. Of note, current differential diagnostic plans now incorporate consideration of modern broad-based next-generation DNA sequencing technologies in the proper clinical context. These recommendations are a general guideline and are not intended as a substitute for clinical judgment or as a protocol for the care of all infants with cholestasis. Broad implementation of these recommendations is expected to reduce the time to the diagnosis of pediatric liver diseases, including biliary atresia, leading to improved outcomes.

Idiopathic adulthood ductopenia manifesting as jaundice in a young male

Idiopathic adulthood ductopenia (IAD) is an unusual disease of unknown etiology which results in chronic cholestatic liver disease. It manifests in young or middle aged adults and is characterized by absence of specific autoantibodies and a loss of interlobular bile ducts. It is a rare cause of cholestatic jaundice with less than 100 cases reported worldwide. We report a case of 18 year male patient who was diagnosed to be suffering from IAD based on clinical, pathological and radiological investigations.

Cholestatic Jaundice in Infants – An Experience in Tertiary Care Hospital

Background: Neonatal cholestasis is defined as prolonged elevation of serum levels of conjugated bilirubin beyond the first 14 days of life. Cholestasis in a newborn can be due to infectious, genetic, metabolic, or undefined abnormalities giving rise to mechanical obstruction of bile flow or to functional impairment of hepatic excretory function and bile secretion. Early detection and timely accurate diagnosis are important for successful treatment and a favorable prognosis. Objective: The present study has been designed to determine the etiology of cholestatic jaundice in infants along with their clinical profile. Methodology: This cross-sectional study was conducted from August 2010 through January 2011 in the Paediatric Gastroenterology &amp; Nutrition Department, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. For the study purpose 40 consecutive cases of cholestatic jaundice were included who fulfilled the inclusion criteria. Result: Biliary atresia was the commonest (42.5%) cause of cholestatic jaundice followed by neonatal hepatitis/ idiopathic neonatal hepatitis. Other causes of cholestatic of the infants were term and of normal birth weight in cases of biliary atresia (BA) but in NH/INH group significant number of infants were preterm and of low birth weight. Mean age at onset of jaundice was 10.1 ± 4.18 days, and mean age at presentation was 113.7 ±15.38 days. In cases of BA Jaundice, intermittent / persistent pale stool, dark urine was found in all cases and hepatomegaly and splenomegaly were found in 88.2% and 64.8% of cases respectively. Ultrasonographically in most of the cases of BA gallbladder was found either small in size or absent or bile ducts were not visualized. In cases of NH/INH visualization of normal gallbladder while fasting and contraction was observed after meal. Histologically typical features BA were found in 12 out of 17 cases of BA and features of early biliary cirrhosis in 4 infants and 10 patients showed features of INH. Conclusion: Biliary atresia was found to be the commonest cause of neonatal cholestasis in the present study. DOI: http://dx.doi.org/10.3329/jbcps.v32i1.21029 J Bangladesh Coll Phys Surg 2014; 32: 9-15

A Case of Jaundice of Obscure Origin

Idiopathic painless jaundice with significant elevations in serum transaminases, occurring in a previously healthy patient, invokes a circumscribed set of possibilities including viral hepatitis, auto-immune hepatitis (AIH) and drug-induced liver injury (DILI). In this described case, common causes of cholestatic jaundice were considered including drug-induced liver injury, viral causes of hepatitis, and auto-immune antibodies. Biliary obstruction was excluded by appropriate imaging studies. Liver biopsy was obtained, though not definitive. After detailed investigation failed to reveal a cause of the jaundice, an empiric trial of steroids was initiated on the possibility that our patient had antibody-negative AIH and not DILI, with an associated grave prognosis. Empiric treatment with prednisone led to rapid resolution of jaundice and to the conclusion that the correct diagnosis was antibody-negative AIH.

Biliary Atresia: 50 Years after the First Kasai

Biliary atresia is a rare neonatal disease of unknown etiology, where obstruction of the biliary tree causes severe cholestasis, leading to biliary cirrhosis and death in the first years of life, if the condition is left untreated. Biliary atresia is the most frequent surgical cause of cholestatic jaundice in neonates and should be evoked whenever this clinical sign is associated with pale stools and hepatomegaly. The treatment of biliary atresia is surgical and currently recommended as a sequence of, eventually, two interventions. During the first months of life a hepatoportoenterostomy (a “Kasai,” modifications of which are discussed in this paper) should be performed, in order to restore the biliary flow to the intestine and lessen further damage to the liver. If this fails and/or the disease progresses towards biliary cirrhosis and life-threatening complications, then liver transplantation is indicated, for which biliary atresia represents the most frequent pediatric indication. Of importance, the earlier the Kasai is performed, the later a liver transplantation is usually needed. This warrants a great degree of awareness of biliary atresia, and the implementation of systematic screening for this life-threatening pathology.

Early Diagnosis of Extrahepatic Biliary Atresia in an Open-Access Medical System

IntroductionBiliary atresia (BA) is the most common cause of cholestatic jaundice in infancy. Early diagnosis and surgical management, ideally before 60 days of age, result in improved outcomes. We aimed to determine the age at diagnosis of BA in the Military Health System (MHS) and to compare the age at diagnosis by access to care models. We hypothesized that children with BA receiving primary care in military facilities have an earlier age at diagnosis due to decreased economic and access barriers.MethodsData for all Tricare enrollees born in fiscal years 2004–2008 with a diagnosis of BA were extracted from MHS databases. Non-parametric tests, Kaplan-Meier curves and log rank tests compared differences in age at diagnosis by type of primary care facility, gender, prematurity and presence of additional anomalies.Results64 subjects were identified within the five year period. Median age at diagnosis was 40 days [range 1–189], with 67% diagnosed by 60 days and 80% by 90 days. 45 (70%) received civilian primary care within the MHS. There was no difference in the median age at diagnosis between subjects in the MHS with civilian primary care vs. military primary care (37 days [1–188] vs. 46 days [1–189]; p = 0.58).ConclusionIn the MHS, two-thirds of infants with biliary atresia are diagnosed prior to 60 days of life. Gender, prematurity or presence of additional anomalies do not affect the timing of diagnosis. Civilian and military primary care models within the MHS make timely diagnoses of biliary atresia at equivalent rates.

Neonatal intrahepatic cholestasis caused by citrin deficiency: prevalence and SLC25A13mutations among thai infants

BackgroundThe most common causes of cholestatic jaundice are biliary atresia and idiopathic neonatal hepatitis (INH). Specific disorders underlying INH, such as various infectious and metabolic causes, including neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) especially, in East Asian populations are increasingly being identified. Since most NICCD infants recovered from liver disease by 1 year of age, they often are misdiagnosed with INH, leading to difficulty in determining the true prevalence of NICCD. Mutation(s) of human SLC25A13 gene encoding a mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), can lead to AGC2 deficiency, resulting in NICCD and an adult-onset fatal disease namely citrullinemia type II (CTLN2). To study the prevalence of NICCD and SLC25A13 mutations in Thai infants, and to compare manifestations of NICCD and non-NICCD, infants with idiopathic cholestatic jaundice or INH were enrolled. Clinical and biochemical data were reviewed. Urine organic acid and plasma amino acids profiles were analyzed. PCR-sequencing of all 18 exons of SLC25A13 and gap PCR for the mutations IVS16ins3kb and Ex16+74_IVS17-32del516 were performed. mRNA were analyzed in selected cases with possible splicing error.ResultsFive out of 39 (12.8%) unrelated infants enrolled in the study were found to have NICCD, of which three had homozygous 851del4 (GTATdel) and two compound heterozygous 851del4/IVS16ins3kb and 851del4/1638ins23, respectively. Two missense mutations (p.M1? and p.R605Q) of unknown functional significance were identified. At the initial presentation, NICCD patients had higher levels of alkaline phosphatase (ALP) and alpha-fetoprotein (AFP) and lower level of alanine aminotransferase (ALT) than those in non-NICCD patients (p< 0.05). NICCD patients showed higher citrulline level and threonine/serine ratio than non-NICCD infants (p< 0.05). Fatty liver was found in 2 NICCD patients. Jaundice resolved in all NICCD and in 87.5% of non-NICCD infants at the median age of 9.5 and 4.0 months, respectively.ConclusionNICCD should be considered in infants with idiopathic cholestasis. The preliminary estimated prevalence of NICCD was calculated to be 1/48,228 with carrier rate of 1/110 among Thai infants. However, this number may be underestimated and required further analysis with mutation screening in larger control population to establish the true prevalence of NICCD and AGC2 deficiency.

Simon Peretz Cats

Liver involvement in Graves’ disease can be seen as a part of autoimmune process or rarely, due to the direct effects of thyrotoxicosis on liver. Hyperthyroidism can also have gastrointestinal...

Cholestatic jaundice in a sample of Iraqi Infants (A hospital based study)

Background: Cholestatic Jaundice is a dilemma facing not only the primary care provider but also the specialist pediatricians in our country.Subjects &amp; methods: Analysis of 50 cases of cholestatic jaundice aged 3 weeks- 18 months were carried out over 18 months in the Gastroenterology &amp; Hepatology unit in the Children Welfare Teaching Hospital, Medical City, and Baghdad. Clinical, biochemical, radiological and histopathological results were recorded.Results: Fifty patients with Cholestatic Jaundice, 28 males &amp;22 females, were evaluated. The main causes of Cholestatic Jaundice were Biliary Atresia in 22 cases (44%)(the mean age of presentation was 4.1 months ), and Neonatal Hepatitis Syndrome of different etiology in 17 cases (34%) (The mean age of presentation was 5.9 months).Galactosemia was the most common cause of metabolic liver disease and CMV was the commonest of the intrauterine viral infections. Two cases of choledocal cyst (4%) and no definite cause was found in 9 cases (18%)Conclusion: Biliary atresia was the most common cause of cholestasis in this study of extra-hepatic type. Different stages of cirrhosis were found in almost all cases of biliary Atresia because of delayed presentation. Clay color stool, hepatomegaly, high alkaline phosphatase &amp; high cholesterol level favor atresia cases. Ultrasonography &amp; liver biopsy prove to be very valuable tools in the differentiation between Biliary Atresia &amp; Neonatal Hepatitis Syndrome.