Cholestatic Jaundice Research Articles

Jaundice as a Rare Manifestation of Epstein-Barr Virus Primary Infection

Epstein-Barr virus (EBV) primary infection usually presents with classic symptoms of infectious mononucleosis (IM) like fever, lymphadenopathies and tonsillopharyngitis. Liver damage is frequently mild and self-limited and there are only a few cases of severe EBV-induced cholestatic hepatitis and jaundice reported in the literature. The authors present the case of a 22-year-old woman who was admitted with acute fever and jaundice. Physical examination revealed posterior cervical lymphadenopathies and painful hepatosplenomegaly. Laboratorial findings suggested an obstructive cause for jaundice but ultrasound and magnetic resonance cholangiopancreatography excluded biliary duct pathology. Heterophile antibodies were negative but EBV-specific antibodies revealed isolated positive viral capsid antigen (VCA) immunoglobin (Ig) M suggesting the diagnosis of early phase of EBV primary infection. The diagnosis of EBV-induced cholestatic hepatitis was confirmed after identification of EBV deoxyribonucleic acid (DNA) in blood and by liver biopsy. Supportive management was provided and, despite an initial clinical deterioration, the patient had a favorable outcome. EBV is a virus with a high prevalence worldwide, mainly subclinical, and jaundice is a rare manifestation of the infection. Although the majority of the patients recover without sequelae, progression to liver failure has been described and a careful assessment for complications is mandatory. Therefore, EBV infection should be included in the comprehensive differential diagnosis of jaundice in all age groups.

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.

Concomitant congenital CMV infection and inherited liver diseases

Inherited liver diseases may present in infancy as cholestatic jaundice progressing to severe hepatic dysfunction. Congenital cytomegalovirus (cCMV) infection may initially involve the liver, yet in otherwise healthy hosts rarely leads to long-term hepatic disease. We report a series of three patients, diagnosed with hereditary liver diseases: progressive familial intrahepatic cholestasis (PFIC) type IV, alpha 1 anti-trypsin deficiency (A1ATD) and Alagille syndrome (ALGS), who were also diagnosed with cCMV infection. All patients were treated with valgancilovir for symptomatic cCMV infection (6–12 months), followed by suppressive dosing in the 2 patients with PFIC and A1ATD. Following 15–24 months of follow-up – the patients with PFIC and A1ATD developed severe liver failure, and the third had ongoing cholestatic disease with stable synthetic function. We propose a significant contribution of cCMV infection to the course of the inherited primary disease, possibly leading to further compromise of the liver. We recommend screening patients with inherited liver disease for cCMV, and considering anti-viral treatment with valganciclovir to delay hepatic disease progression.

A Case Report on Methimazole-Induced Cholestatic Jaundice in an Elderly Man With Hyperthyroidism

Background: The early detection and diagnosis of the causes of jaundice in a hyperthyroid patient taking antithyroid medications are paramount for the appropriate management of these patients. Clinical Case: A 72 year old male is admitted due to septic shock secondary to pneumonia and funguria, acute kidney injury secondary to sepsis, type 2 diabetes mellitus, uncontrolled and Graves’ disease with thyroid nodules (Tirads 4). On physical examination, he has icteresia and generalized jaundice. Methimazole was started 12 days ago. Initial tests were consistent with a cholestatic pattern of jaundice: slightly elevated alanine aminotransferase 70 U/L (16-63), aspartate aminotransferase 84 U/L (15-37) and significantly elevated alkaline phosphatase 662 U/L (46-116), total bilirubin 12.16 mg/dl (0.20-1.0), conjugated bilirubin 11.29 mg/dl (0-0.20) and unconjugated bilirubin 0.87 mg/dl (0-0.80). He has hypoalbuminemia and normal prothrombin time. He has negative anti-Smith antibody, anti-ribonucleoprotein, anti-mitochondrial antibody, and positive anti-nuclear antibody 1:160 speckled pattern. Hepatitis Profile showed chronic hepatitis A infection. Upper Abdomen Ultrasound showed ill-defined border in the left hepatic lobe; intrahepatic ducts and common bile duct are not dilated; gallbladder is contracted with no evident intraluminal echoes. Whole Abdomen with 4-phase Dynamic Liver CT Scan showed multiple ill-defined hypoattenuating lesions in the entire liver parenchyma; intrahepatic ducts, common bile duct, and pancreatic duct are not dilated; and gallbladder is normal in size without intraluminal calculus with possible metastases at spleen, left adrenal gland and tail of pancreas. He has normal AFP and elevated CEA. Methimazole was discontinued at admission and was started on Hydrocortisone 100 mg/IV every 8 hrs. Repeat liver profile panel showed decreasing trends after 4 days of holding methimazole. Repeat fT4 after 6 days of high dose hydrocortisone showed a decrease from 3.09 ng/dl to 1.98 ng/dl (0.89-1.76). Hydrocortisone was continued and tapered accordingly. Plans for RAI discussed. Conclusion: This case emphasizes the need to be vigilant for the very rare but serious adverse events of antithyroid medications.

Spontaneous resolution of prolonged cholestatic jaundice following hepatitis

In children, acute viral hepatitis-A infection is usually a self-limiting illness. In most children, it resolves uneventfully within weeks from the onset of disease. However, rare presentations like acute acalculous cholecystitis and persistent cholestatic jaundice have been reported. We report on a 7-year-old boy with prolonged cholestatic jaundice, which resolved without steroid treatment.

ACG Clinical Guideline: Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury.

Idiosyncratic drug-induced liver injury (DILI) is common in gastroenterology and hepatology practices, and it can have multiple presentations, ranging from asymptomatic elevations in liver biochemistries to hepatocellular or cholestatic jaundice, liver failure, or chronic hepatitis. Antimicrobials, herbal and dietary supplements, and anticancer therapeutics (e.g., tyrosine kinase inhibitors or immune-checkpoint inhibitors) are the most common classes of agents to cause DILI in the Western world. DILI is a diagnosis of exclusion, and thus, careful assessment for other etiologies of liver disease should be undertaken before establishing a diagnosis of DILI. Model for end-stage liver disease score and comorbidity burden are important determinants of mortality in patients presenting with suspected DILI. DILI carries a mortality rate up to 10% when hepatocellular jaundice is present. Patients with DILI who develop progressive jaundice with or without coagulopathy should be referred to a tertiary care center for specialized care, including consideration for potential liver transplantation. The role of systemic corticosteroids is controversial, but they may be administered when a liver injury event cannot be distinguished between autoimmune hepatitis or DILI or when a DILI event presents with prominent autoimmune hepatitis features.

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.

A ZFYVE19 gene mutation associated with neonatal cholestasis and cilia dysfunction: case report with a novel pathogenic variant

BackgroundZFYVE19 (Zinc Finger FYVE-Type Containing 19) mutations have most recently been associated to a novel type of high gamma-glutamyl transpeptidase (GGT), non-syndromic, neonatal-onset intrahepatic chronic cholestasis possibly associated to cilia dysfunction. Herein, we report a new case with further studies of whole exome sequencing (WES) and immunofluorescence in primary cilia of her cultured fibroblasts which confirm the observation.ResultsA now 5-year-old girl born to clinically healthy consanguineous Moroccan parents was assessed at 59 days of life due to severe cholestatic jaundice with increased serum bile acids and GGT, and preserved hepatocellular synthetic function. Despite fibrosis/cirrhosis and biliary ducts proliferation on liver biopsy suggested an extrahepatic biliary obstacle, normal intra-operatory cholangiography excluded biliary atresia. Under choleretic treatment, she maintained a clinically stable anicteric cholestasis but developped hyperlipidemia. After exclusion of the main causes of cholestasis by multiple tests, abnormal concentrations of sterols and WES led to a diagnosis of hereditary sitosterolemia (OMIM #618666), likely unrelated to her cholestasis. Further sequencing investigation revealed a homozygous non-sense mutation (p.Arg223Ter) in ZFYVE19 leading to a 222 aa truncated protein and present in both heterozygous parents. Immunofluorescence analysis of primary cilia on cultured skin fibroblasts showed a ciliary phenotype mainly defined by fragmented cilia and centrioles abnormalities.ConclusionsOur findings are consistent with and expands the recent evidence linking ZFYVE19 to a novel, likely non-syndromic, high GGT-PFIC phenotype with neonatal onset. Due to the possible role of ZFYVE19 in cilia function and the unprecedented coexistence of a coincidental hereditary sterol disorder in our case, continuous monitoring will be necessary to substantiate type of liver disease progression and/or possible emergence of a multisystemic involvement. What mentioned above confirms that the application of WES in children with undiagnosed cholestasis may lead to the identification of new causative genes, widening the knowledge on the pathophysiology.

Ultrasound shear wave elastography: does it add value to gray-scale ultrasound imaging in differentiating biliary atresia from other causes of neonatal jaundice?

Neonatal/infantile jaundice is relatively common, and most cases resolve spontaneously. However, in the setting of unresolved neonatal cholestasis, a prompt and accurate assessment for biliary atresia is vital to prevent poor outcomes. To determine whether shear wave elastography (SWE) alone or combined with gray-scale imaging improves the diagnostic performance of US in discriminating biliary atresia from other causes of neonatal jaundice over that of gray-scale imaging alone. Infants referred for cholestatic jaundice were assessed with SWE and gray-scale US. On gray-scale US, two radiology readers assessed liver heterogeneity, presence of the triangular cord sign, hepatic artery size, presence/absence of common bile duct and gallbladder, and gallbladder shape; associated interobserver correlation coefficients (ICC) were calculated. SWE speeds were performed on a Siemens S3000 using 6C2 and 9L4 transducers with both point and two-dimensional (2-D) SWE US. Both univariable and multivariable analyses were performed, as were receiver operating characteristic curves (ROC) and statistical significance tests (chi-squared, analysis of variance, t-test and Wilcoxon rank sum) when appropriate. There were 212 infants with biliary atresia and 106 without biliary atresia. The median shear wave speed (SWS) for biliary atresia cases was significantly higher (P<0.001) than for non-biliary-atresia cases for all acquisition modes. For reference, the median L9 point SWS was 2.1m/s (interquartile range [IQR] 1.7-2.4m/s) in infants with biliary atresia and 1.5m/s (IQR 1.3-1.9m/s) in infants without biliary atresia (P<0.001). All gray-scale US findings were significantly different between biliary-atresia and non-biliary-atresia cohorts (P<0.001), intraclass correlation coefficient (ICC) range 0.7-1.0. Triangular cord sign was most predictive of biliary atresia independent of other gray-scale findings or SWS - 96% specific and 88% sensitive. Multistep univariable/multivariable analysis of both gray-scale findings and SWE resulted in three groups being predictive of biliary atresia likelihood. Abnormal common bile duct/gallbladder and enlarged hepatic artery were highly predictive of biliary atresia independent of SWS (100% for girls and 95-100% for boys). Presence of both the common bile duct and the gallbladder along with a normal hepatic artery usually excluded biliary atresia independent of SWS. Other gray-scale combinations were equivocal, and including SWE improved discrimination between biliary-atresia and non-biliary-atresia cases. Shear wave elastography independent of gray-scale US significantly differentiated biliary-atresia from non-biliary-atresia cases. However, gray-scale findings were more predictive of biliary atresia than elastography. SWE was useful for differentiating biliary-atresia from non-biliary-atresia cases in the setting of equivocal gray-scale findings.

Hepatic Disfunction in Renal Cell Carcinoma: A Stauffer Syndrome Variant

Cholestatic jaundice is usually linked to a malignant disease when it is secondary to a mechanical obstruction of the bile duct or due to hepatic metastasis. As a paraneoplastic syndrome, cholestasis has been described in lymphoproliferative disorders, in prostate cancer and as the Stauffer syndrome with non-metastatic dysfunction in patients with renal cell carcinoma (RCC). We present the case of a 61 year old patient with a paraneoplastic manifestation with cholestatic jaundice due to RCC with kindney and lung metastases. Clinical characteristics of patients with RCC vary and sometimes manifest in a peculiar way. Cholestatic jaundice is a rare paraneoplastic syndrome associated with RCC and with the exclusion of more frequent causes, it should be taken into account in the differential diagnosis. This rare but possible association requires prompt recognition, as prognosis correlates with disease stage and influences patient’s overall survival, and an early recognition of this syndrome may improve, sometimes, patients’ outcome.

Clinicobiochemical Parameters and Predictors of Liver Disease in Hospitalized Asian Indian Pregnant Women in a Tertiary Care Center in Northern India

Introduction During pregnancy, liver dysfunction is more frequent than expected and may require specialized care. For the early diagnosis, it is important to determine if changes in liver physiology may develop into liver disease. Liver disease during pregnancy may require intervention from a hepatologist for adequate monitoring of mother-fetus health outcomes. This study was aimed to evaluate the clinical profile and predictors of maternal mortality in patients with liver diseases among Asian-Indian-females.MethodsWe conducted a prospective, open-label, consecutive all-comers study of 2,663 pregnant Asian Indian women admitted in the hospital, which included 92 with liver dysfunction. The medical aspects of the pregnancy were then followed prospectively with laboratory and clinical data during the hospital stay and analyzed. The current study was approved by the Institutional Ethical Committee.ResultsWe found that 92 out of 2,663 patients had liver dysfunction with a prevalence of 3.45%. Fifty-four (58.7%) patients had icterus followed by fever in 23 (25.0%), hypertension in 22 (23.9%), central nervous system manifestations in 21 (22.8%), abdominal pain in 19 (20.6%), vomiting in 19 (20.6%), and pruritus in six (6.5%). Predictors of maternal mortality were icterus (p = 0.04), hepatomegaly (p = 0.04), presenting serum-bilirubin greater than 10 milligram% (mg%) (p = 0.008). The most common etiology was acute viral hepatitis (45.6%), followed by a hypertensive disorder of pregnancy (29.3%), acute fatty liver of pregnancy (1.1%), cholestatic jaundice (9.8%), hyperemesis gravidarum (2.2%), septicemic hepatitis (3.3%), dengue immunoglobulin M (IgM), and plasmodium vivax malaria antigen positive in (2.2%) each. Four patients (4.3%) were leptospira IgM reactive and had co-infection with hepatitis E virus. There was one patient (1.1%) with underlying chronic liver disease. Idiopathic liver disease was present in 5.4% of patients.ConclusionLiver disease is relatively common in Indian pregnant women. It is associated with high maternal and perinatal mortality, even in a tertiary referral center. When managing pregnancy in a tertiary care center, for adequate follow-up of the disease and to prevent adverse consequences for mother and child, it is important to discard liver alterations early. For this purpose, liver disease during pregnancy needs early diagnosis for proper management. Furthermore, it is difficult to manage patients with preexisting liver disease, and it may require specialized intervention from a hepatologist and a gastroenterologist.

Conjugated hyperbilirubinemia among infants with hyperinsulinemic hypoglycemia.

From clinical practice, we noted that a subset of neonates with hyperinsulinism develop conjugated hyperbilirubinemia. A relationship between these two conditions has not been previously described. We aimed to assess the incidence of cholestasis in a cohort of neonates with hyperinsulinism and describe their clinical characteristics. In a retrospective cohort of 63 neonates with hyperinsulinism, 48% developed cholestasis (conjugated bilirubin > 17 μmol/L) with a median maximum conjugated bilirubin of 81 [21 to 191] μmol/L. A history of fetal distress (RR 2.3 [1.24-4.45], p < 0.01) and prematurity (RR 2.0 [1.23-3.26], p <0.01) was associated with the development of cholestasis, but not parental nutrition or other pharmacological treatments. An underlying etiology for the cholestasis was only found in 1 patient, and in all cases the cholestasis spontaneously improved.Conclusions: A significant percentage of infants with hyperinsulinism develop idiopathic, spontaneously resolving, conjugated hyperbilirubinemia. The association with a history of fetal distress potentially suggests that intrauterine factors leading to hyperinsulinism may also predispose towards conjugated hyperbilirubinemia. While the presence of neonatal cholestatic jaundice warrants timely investigations to exclude important underling etiologies, if validated, these findings may support a less invasive diagnostic workup of conjugated hyperbilirubinemia in infants with co-existent hyperinsulinism. What is Known: • Hyperinsulinism and conjugated hyperbilirubinemia are two common presentations in neonates. • A clinical association between the two conditions has not been described. What is New: • A significant proportion of infants with hyperinsulinism develop idiopathic, spontaneously resolving conjugated hyperbilirubinemia. • Increased risk for cholestasis in this patient population is associated with fetal distress and prematurity but not parental nutrition.

A Study on Seroprevalence of Hepatotropic Viruses in Neonatal Cholestasis Patients at a Tertiary Care Hospital of Central India

Introduction: Neonatal Cholestasis (NC) is defined as conjugated hyperbilirubinaemia in infancy, Diverse aetiologies and several disorders are responsible for this hepatobiliary dysfunction. Hepatotropic viral infection may have an important role in the pathogenesis of NC and related clinical outcomes. Aim: This study was aimed to estimate the seroprevalence of the hepatotropic viruses and their possible role in neonates presenting with cholestatic jaundice. Materials and Methods: This retrospective study included 51 infants who presented with cholestatic jaundice. Serum samples were collected and screened for the hepatotropic viruses. The presence of serological markers to Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Hepatitis C (HCV), Hepatitis E (HEV), Herpes Simplex Virus (HSV) and Rubella were tested using enzyme-linked immunosorbent assays. Hepatitis B Virus (HBV) serostatus was determined by using rapid card tests. Results: Of the 51 cases, 4 (7.6%) patients presented with biliary atresia. Seroprevalence of CMV (23.5%) was found to be more predominant followed by EBV (13.7%), HCV (5.8%), HEV (5.8%), HSV (1.9%) and Rubella (1.9%). Co-infections were found in 7 (13.7%) cases and CMV-EBV co-infection being the most common. Conclusion: The presence of specific serological markers to hepatotropic viruses in the NC cases strongly suggests their aetiological role in this disorder. To the best of the knowledge, this is the first report documenting the seroprevalence of hepatotropic viruses in NC patients from Central India.

Primary Biliary Cholangitis and Type 1 Diabetes in A Male Patient: A Case Report

Primary Biliary Cholangitis (PBC) isa cholestatic disease of autoimmune origin characterized by the destruction of small to medium size intrahepatic bile ducts due to lymphocytic infiltration. The diagnosis is made by the presence of Anti-Mitochondrial Antibodies (AMAs) specific for the disease. PBC typically affects middle-aged women and is often associated with other autoimmune pathologies which are in decreasing order of frequency: Sjogren's syndrome, autoimmune dysthyroidism, scleroderma, rheumatoid arthritis, lupus and celiac diseasewhich are also more common in women. Few clinical studies evaluate the presentation of PBC in men with concomitant type 1 diabetes due to its low incidence compared to the prevalence of PBC in women.This case report presents that of a male patient with type 1 diabetes, admitted for cholestatic jaundice with pruritus, and in whom the diagnosis of PBC was only made late in the cirrhosis stage

Doença de Kawasaki atípica associada à síndrome colestática: relato de caso

OBJECTIVES: To report the case of a child with atipical Kawasaki disease associated with cholestatic syndrome. Kawasaki disease is an inflammatory syndrome that affects small and medium-sized vases, which cause is unknown. The diagnostic is clinical and based in classic criterions, which are commonly reported symptoms, does not including cholestatic jaundice nor hepatomegaly because they are un-usual findings. CASE REPORT: 6-year-old female presented persistent high fever, rash and gastrointes-tinal symptoms. She developed with conjunctival injection, strawberry tongue, and cracked lips, with-out improvement of the fever after the empiric antibiotic treatment. In elapsing of the disease, the rash got improvement and appeared cholestatic syndrome and classic symptoms of the disease of complete Kawasaki (unilateral cervical lymphadenopaty, conjunctival injection, and hand desquama-tion), that it made possible her diagnosis and treatment, with improvement of cholestatic syndrome, without aneurysm appearance. CONCLUSIONS: This paper shows the importance of including Kawasaki disease as differential diagnosis in cases of jaundice feverish syndromes, allowing their treatment in skilled time end prevent complications.

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.

Prolonged Cholestatic Jaundice as an Atypical Manifestation of Acute Hepatitis A Virus (HAV) Infection in Children

This article reports two cases of prolonged cholestatic type hepatitis A, a rare clinical manifestation of hepatitis A virus infection in children. Acute hepatitis A virus infection typically resolves spontaneously in 90% of the cases. In children, complete recovery usually occurs in most of the cases within two months. Occasionally, the cholestatic variety may persist for several months, characterized by intense pruritus and prolonged conjugated hyperbilirubinemia. The diagnosis is based on the presence of IgM anti-HAV, symptoms longer than 8 weeks, bilirubin concentration &gt;10 g/dL in the absence of substantial hepatocellular and biliary damage. Use of only ursodeoxycholicacid (UDCA) rather than the combined use of UDCA and corticosteroid is sufficient.

Systematic Analysis of Protein Targets Associated with Adverse Events of Drugs from Clinical Trials and Postmarketing Reports.

Adverse drug reactions (ADRs) are undesired effects of medicines that can harm patients and are a significant source of attrition in drug development. ADRs are anticipated by routinely screening drugs against secondary pharmacology protein panels. However, there is still a lack of quantitative information on the links between these off-target proteins and the reporting of ADRs in humans. Here, we present a systematic analysis of associations between measured and predicted in vitro bioactivities of drugs and adverse events (AEs) in humans from two sources of data: the Side Effect Resource, derived from clinical trials, and the Food and Drug Administration Adverse Event Reporting System, derived from postmarketing surveillance. The ratio of a drug's therapeutic unbound plasma concentration over the drug's in vitro potency against a given protein was used to select proteins most likely to be relevant to in vivo effects. In examining individual target bioactivities as predictors of AEs, we found a trade-off between the positive predictive value and the fraction of drugs with AEs that can be detected. However, considering sets of multiple targets for the same AE can help identify a greater fraction of AE-associated drugs. Of the 45 targets with statistically significant associations to AEs, 30 are included on existing safety target panels. The remaining 15 targets include 9 carbonic anhydrases, of which CA5B is significantly associated with cholestatic jaundice. We include the full quantitative data on associations between measured and predicted in vitro bioactivities and AEs in humans in this work, which can be used to make a more informed selection of safety profiling targets.

Bacteremia-Induced Cholestatic Jaundice as a Major Manifestation of Pneumococcal Infection in a Healthy Toddler

AbstractThe development of pneumococcal conjugate vaccines has substantially decreased the incidence of invasive pneumococcal diseases. However, the incidence of bacteremia due to nonvaccine serotypes has increased. Therefore, it is important to recognize the symptoms and complications of pneumococcal infection to expedite diagnosis. Herein, we report the case of a 22-month-old patient diagnosed with pneumococcal bacteremia who presented with cholestatic jaundice and fever without any other signs of systemic sepsis. The patient's condition improved soon after antibacterial therapy. Other causes of jaundice were possibly ruled out based on the screening test for viral hepatitis, and there were no abnormal findings on abdominal ultrasonography. Therefore, the present case suggests that cholestatic jaundice could be a manifestation of pneumococcal bacteremia.

Incidence and Causes of Liver Dysfunction in Neonatal Intensive Care Unit in Benha Children Hospital

Liver dysfunction plays a significant role in the Intensive Care Unit [ICU] patients’ morbidity and mortality. Metabolic, hemodynamic and incendiary components contribute in liver harm. Hemorrhagic stun. The examination planned to evaluate the rate of liver brokenness in neonatal emergency unit patients in pediatric office. This investigation was planned examination which led on 150 cases in Neonatal emergency unit Benha youngsters clinic which is a shut multidisciplinary optional NICU during the examination which was a half year [1/7/2018 – 31/12/2018]. All included patients were exposed to the accompanying: History taking, assessment and Laboratory examinations included Liver capacity tests including: Patients with hepatic friendship were characterized as the individuals who had any raised transaminases or cholestatic jaundice or hepatomegly dependent on clinical assessment and research center outcomes. Liver brokenness happened in 45 [30%] of the examined gathering. There were no factually critical distinction between Patients with hepatic warmth and Patients without hepatic fondness with respect to Sex. The death rate among cases was 14%. There was no factually critical distinction between Patients with hepatic fondness and Patients without hepatic love with respect to result. Liver brokenness are normal in NICU speaking to around 33% of cases.Key words: Liver dysfunction- neonates intensive care unit- incidence.