Prolonged Cholestatic Jaundice Research Articles

Global Adrenal Insufficiency in Two Independent Patients Carrying the Same Homozygous c.172A>G, p.(Thr58Ala) Mutation in the TBX19 Gene.

TBX19 mutations cause isolated ACTH-deficiency. While this classically results in severe hypocortisolism, potential consequences for mineralocorticoid biosynthesis have not been described to date. Liquid chromatography mass spectrometry (LC-MS/MS) and gas chromatography mass spectrometry (GC-MS) allow novel insights into the steroid metabolism of pediatric endocrine diseases. Patient 1 (female) presented right after birth with hypoglycemia and hyponatremia (minimum sodium 126 mmol/L). She recovered under therapy with hydrocortisone, fludrocortisone and initial NaCl. Patient 2 (male) presented after birth with prolonged cholestatic jaundice. Only at the age of 3.5 months, repeated episodes of hypoglycemia occurred. Both patients showed severely reduced ACTH. LC-MS/MS analyses on plasma samples demonstrated combined reduced glucocorticoid- and mineralocorticoid biosynthesis confirmed by GC-MS analyses on spot urine. In contrast to patient 1, patient 2 (currently 8 years old) never suffered from hyponatremia. Both patients carry the same homozygous c.172A>G, p.(Thr58Ala) mutation in the TBX19 gene proving isolated ACTH-deficiency. Isolated ACTH-deficiency can be associated with reduced mineralocorticoids and hyponatremia. We hypothesize that sufficient pituitary ACTH secretion is an important predisposition for regular adrenal mineralocorticoid biosynthesis.

RESISTANT AND PROLONGED HYPOGLYCEMIA COMPLICATING THE COURSE OF SEVERE ACUTE HEPATITIS A : A CASE REPORT

Acute liver failure (ALF) is a severe and acute liver injury which presents infrequently. Hepatitis A virus (HAV) occurs commonly in resource poor regions like India. It is one of the commonest cause of acute hepatitis in India, but rarely progressed to ALF. Hypoglycemia in association with liver disease has generally been considered as uncommon entity occurring primarily in circumstances of rapid massive hepatic necrosis. Previous retrospective studies had emphasized rarity of hypoglycemia in viral hepatitis. We present a case of 2 year boy who developed resistant and prolonged hypoglycemia secondary to Hepatitis A induced acute liver failure. Along with difcult to manage hypoglycemia his disease was also complicated with Hepatic encephalopathy and prolonged cholestatic Jaundice. He had a stormy hospital course but survived without Sequelae. We report this case with the aim to raise awareness about this rare but fatal metabolic complication of Hepatitis A infection as viral hepatitis has become a global health-care problem.

A serious and unusual presentation of congenital isolated ACTH deficiency due to TBX19 mutation, beyond the neonatal period.

SummaryCongenital isolated adrenocorticotrophic hormone (ACTH) deficiency due to T-box transcription factor-19 (TBX19 mutation) (MIM 201400; ORPHA 199296) usually presents in the neonatal period with severe hypoglycemia, seizures, and sometimes prolonged cholestatic jaundice. We report a case with an unusual presentation that delayed the diagnosis. A 9-month-old female patient with no relevant personal history was admitted to the emergency department due to a hypoglycemic seizure in the context of acute gastroenteritis. There was rapid recovery after glucose administration. At age 4, she presented with tonic-clonic seizures, fever, and gastrointestinal symptoms and came to need support in an intensive care unit. Low serum cortisol was documented and hydrocortisone was initiated. After normalization of inflammatory parameters, the patient was discharged with hydrocortisone. The genetic investigation was requested and compound heterozygous mutations in TBX19 were detected. This is a rare case of presentation of TBX19 mutation outside the neonatal period and in the setting of acute disease, which presented a diagnostic challenge.Learning pointsCongenital isolated adrenocorticotrophic hormone deficiency due to TBX19 mutation usually presents with neonatal hypoglycemia and prolonged cholestatic jaundice.An uneventful neonatal period, however, does not exclude the diagnosis as the disease may be asymptomatic at this stage.In the context of idiopathic hypoglycemia, even in the context of acute disease, hypocortisolism must always be excluded.Genetic evaluation should be performed in cases of congenital central hypocortisolism to allow proper counselling.

Prolonged Cholestatic Jaundice Associated with Carnitine Palmitoyltransferase IA Deficiency.

Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a type of fatty acid oxidation disorder in which long chain fatty acids cannot be transported into mitochondria for further processing and storage in our body. Typically, the patients present with lethargy, hypoglycemia, and raised serum transaminase levels before 2 years of age. Cholestatic jaundice as manifestation of this deficiency has been reported rarely; here, we report an adolescent male with CPT1A deficiency who developed prolonged cholestatic jaundice following a febrile illness.

Prolonged Cholestasis Due to Hepatitis A Virus Infection in a Young Adolescent Male with a Known Case of Hemoglobin E Disease: Early Response to Steroid Therapy

Background: Acute hepatitis due to hepatitis A virus infection is a self-limiting mild disease. Sometimes, it may have an atypical course in few percentages. We reviewed with characteristics, response to steroid therapy, and outcome of prolonged cholestatic jaundice in hepatitis A virus infection. Case Summary: We analyzed acute hepatitis with a prolonged cholestatic course due to hepatitis A virus infection in an adolescent with preexisting hemoglobin E disease. Bilirubin was gradually increasing, the maximum total bilirubin was 48.3 mg/dl, and direct 46.6 mg/dl at day 50 of symptoms onset. After that, the steroid was started along with ursodeoxycholic acid. The patient gradually improved clinically and biochemically. Conclusion: Hepatitis A virus infection may cause prolonged cholestatic severe jaundice in a patient with preexisting congenital hemolytic disease. Steroid therapy may induce early recovery.

Prolonged Cholestasis Due to Hepatitis A Virus Infection in a Young Adolescent Male with a Known Case of Hemoglobin E Disease: Early Response to Steroid Therapy

Background: Acute hepatitis due to hepatitis A virus infection is a self-limiting mild disease. Sometimes, it may have an atypical course in few percentages. We reviewed with characteristics, response to steroid therapy, and outcome of prolonged cholestatic jaundice in hepatitis A virus infection. Case Summary: We analyzed acute hepatitis with a prolonged cholestatic course due to hepatitis A virus infection in an adolescent with preexisting hemoglobin E disease. Bilirubin was gradually increasing, the maximum total bilirubin was 48.3 mg/dl, and direct 46.6 mg/dl at day 50 of symptoms onset. After that, the steroid was started along with ursodeoxycholic acid. The patient gradually improved clinically and biochemically. Conclusion: Hepatitis A virus infection may cause prolonged cholestatic severe jaundice in a patient with preexisting congenital hemolytic disease. Steroid therapy may induce early recovery.

Pediatric Adrenal Insufficiency: Challenges and Solutions.

Adrenal insufficiency is an insidious diagnosis that can be initially misdiagnosed as other life-threatening endocrine conditions, as well as sepsis, metabolic disorders, or cardiovascular disease. In newborns, cortisol deficiency causes delayed bile acid synthesis and transport maturation, determining prolonged cholestatic jaundice. Subclinical adrenal insufficiency is a particular challenge for a pediatric endocrinologist, representing the preclinical stage of acute adrenal insufficiency. Although often included in the extensive work-up of an unwell child, a single cortisol value is usually difficult to interpret; therefore, in most cases, a dynamic test is required for diagnosis to assess the hypothalamic-pituitary-adrenal axis. Stimulation tests using corticotropin analogs are recommended as first-line for diagnosis. All patients with adrenal insufficiency need long-term glucocorticoid replacement therapy, and oral hydrocortisone is the first-choice replacement treatment in pediatric. However, children that experience low cortisol concentrations and symptoms of cortisol insufficiency can take advantage using a modified release hydrocortisone formulation. The acute adrenal crisis is a life-threatening condition in all ages, treatment is effective if administered promptly, and it must not be delayed for any reason.

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.

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 >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.

Neonatal cholestasis due to citrin deficiency: diagnostic pitfalls

Citrin deficiency can manifest in newborns or infants as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). The paper presents a case of Polish NICCD patient presenting with low birth weight, failure to thrive, prolonged cholestatic jaundice with coagulopathy and hypoalbuminemia with normal results of MS/MS newborn screening but with high blood citrulline level observed at 3 months of age. Unreported findings included N-hypoglycosylation and increased serum very-long-chain fatty acids (VLCFA), probably secondary to liver impairment. Final diagnosis was established based on whole-exome sequencing (WES) analysis.

Pathophysiological aspects of liver damage in children with alpha-1-antitrypsin deficiency

Alpha-1-antitrypsin deficiency is an autosomal recessive disease characterized by both liver damage and lung disease in children and adults because of a decrease in the serum protein content due to the mutations in the PI (proteinase inhibitor) gene. The majority of liver diseases are associated with a homozygous mutation of the Z allele. There are many variations of clinical manifestations of the liver disease in children with the PI*ZZ genotype. In the neonatal period, liver disease is usually cholestatic; and it is accompanied by a prolonged cholestatic jaundice, skin itching, which can be determined only later (after 6 months), decreased appetite and bad weight gain, hepato- and splenomegaly. The article describes the pathophysiology of liver damage in children with alpha-1-antitrypsin deficiency. The authors provide their recommendations for the management of children with suspected and confirmed alpha-1-antitrypsin deficiency.

Donʼt Ask, Donʼt Tell: A Lesson on Evaluating Acute Hepatitis

Acute hepatitis A virus (HAV) infection is common in developing countries. It can range from asymptomatic to fulminant hepatitis. The mean peak of total bilirubin in acute HAV infection is usually less than 10 mg/dL with mean jaundice lasting about 4 weeks. Cases of prolonged or relapsing cholestatic HAV were reported at a global incidence of 5-10%. Acute HAV infection with prolonged cholestatic jaundice (PCJ) is rare. We present a severe prolonged cholestatic HAV infection likely complicated by concurrent Chikungunya virus infection and drug induced liver injury. A 39 year old female, born in India, presented to our hospital with subjective fevers, malaise, and myalgias for 3 weeks. She returned from a trip to India 1 month ago. On admission she had a temperature of 100.1°F. Her physical exam was within normal limits with no documented hepatomegaly. Her initial blood work showed elevated transaminases (aspartate aminotransferase (AST u/L) 122, alanine aminotransferase (ALT u/L) 143)with normal alkaline phosphatase (ALP) and total bilirubin (TB). Three days into her admission she showed some clinical improvement but with worsening of AST to 1958 and ALT to 1605 reaching a peak of AST 3804 and ALT 3335; ALP remained normal and TB increased to 4.0 mg/dL. US of abdomen showed hepatic steatosis. Viral markers were positive for HAV IgM but negative for acute EBV, CMV, HBV, HCV and HEV infection. Her autoimmune panel was negative. She was discharged 1 week later with clinical improvement; AST 556 and ALT 1418, ALP 77 and INR 1.58. Her TB remained elevated to 7.6. She was readmitted to the hospital 2 weeks later with pruritus and worsening fatigue. Her AST was 88 and ALT 59, with ALP of 148 and a TB of 23.4. Her INR was 2.09. A repeat US showed no biliary ductal dilation or stones. She tested positive for Chikungunya IgM. She admitted to ingesting multiple herbal products. Her liver tests normalized at 4 months with positive HAV and Chikungunya IgG.FigureFigureFigureWe present a severe prolonged cholestatic HAV infection likely complicated by concurrent Chikungunya infection and drug induced liver injury. Acute HAV infection with prolonged cholestatic jaundice (PCJ) is rare. Acute Chikungunya has been documented as a cause of acute cholestatic hepatitis. A thorough history of drug exposure is essential in the evaluation of cholestatic liver injury. Furthermore, CDC recommendation for HAV vaccination for travelers should be reinforced even on immigrants from endemic countries.

Congenital central hypothyroidism in a neonate born to thyrotoxic mother

Maternal thyrotoxicosis is associated with significant risk of low birth weight premature & small for gestational age neonates; as well as intrauterine death. The abnormal thyroid functions seen in babies of thyrotoxic mothers include neonatal hyperthyroidism, transient neonatal primary hypothyroidism and transient central hypothyroidism. Transient central hypothyroidism is a unique entity which is not widely recognized. It is usually seen in neonates born from mothers with uncontrolled thyrotoxicosis. We report a case of congenital central hypothyroidism in a neonate, who born to thyrotoxic Rh negative mother. Neonate presented with anemia and prolonged cholestatic jaundice. It is important to recognize this condition timely as its delayed diagnosis & treatment results in permanent mental retardation. To avoid missing of this condition, FT4 should be monitored serially in all infants born to thyrotoxic mothers. With thyroid hormone replacement therapy there was tremendous improvement both clinically as well as biochemically in our case.

HYPOTHALAMIC HYPOTHYROIDISM IN A NEWBORN WITH CLASSIC GALACTOSEMIA: CASE REPORT

Objective – To report a rare case of classic galactosemia and hypothalamic hypothyroidism. Case report – A male newborn presented with failure to thrive, prolonged cholestatic jaundice, sepsis and hypothyroidism. Hydration, empiric antibiotics and L-thyroxine treatment were started. Since classic galactosemia had been suspected and confirmed, a galactose-restricted diet was commenced. The patient’s health status improved, including the fast recovery of the thyroid function tests. L-thyroxine dosage was decreased two weeks after starting the therapy and completely stopped two months after starting the galactose-restricted diet. Conclusion – Further investigations are necessary to establish whether such patients require treatment with L-thyroxine or a galactose-restricted diet is sufficient. It may be useful to perform thyroid function tests also in infants diagnosed with classic galactosemia.

Prolonged Cholestasis After Endoscopic Retrograde Cholangiopancreatography

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) is commonly associated with post-procedure infection, pancreatitis, hemorrhage, and perforation. Prolonged cholestatic jaundice following successful therapeutic ERCP is a rarely reported complication. We present a case of persistently abnormal liver associated enzymes and jaundice in a patient who underwent ERCP for choledocholelithiasis. Case Report: A 53-year-old white male with non-insulin dependent diabetes and congestive heart failure presented with a 3-week duration of abdominal pain and jaundice. He was afebrile and right upper quadrant tenderness was noted on exam. Laboratory tests revealed an elevated alkaline phosphatase (202 units/L), total bilirubin (15.9 mg/dL) with an increased direct component (11.8 mg/dL), and modest rise in aspartate transferase (AST; 92 units/L) and alanine transferase (ALT; 59 units/L). White count and lipase were normal. The patient denied recent travel, new medications, illicit drug use, or alcohol intake. Magnetic resonance cholangiopancreatography (MRCP) showed dilated intra- and extrahepatic bile ducts with tapering of the distal common bile duct (CBD) near the ampulla. Subsequent ERCP visualized CBD dilation to 12 mm and choledocholelithiasis. Sphincterotomy was performed and a 7 Fr x 5 cm double-pigtail stent was placed. During routine follow-up 3 weeks later, the patient was found to have a total bilirubin (23.3 mg/dL) and direct component (19.8 mg/dL). AST and ALT were within normal limits. The patient appeared jaundiced but was otherwise asymptomatic. MRCP noted dilation of the intra- and extrahepatic ducts with minimal CBD dilation. Given that no choledocholelithiasis was seen on imaging, repeat ERCP was not immediately done. The patient subsequently underwent a HIDA scan that showed minimal delay in transit of tracer from liver to small bowel. Ceruloplasmin and iron studies were normal. Antinuclear and antismooth muscle antibodies were negative. Liver biopsy showed cholestatic hepatocellular injury with mild lobular inflammation. No evidence of hepatitis, cirrhosis, or hepatic congestion was noted. He is scheduled to undergo a repeat ERCP, and is being treated with ursodeoxycholic acid for minor itching. Discussion: Post-ERCP cholestatic jaundice is rare and thought to be due to hepatocellular injury from contrast dye, or from antibiotic use for prophylaxis or preceding infection. Liver biopsy is recommended to rule out secondary causes of cholestasis such as drug use, autoimmune pathology, or hepatic congestion. Treatment is usually with ursodeoxycholic and steroids.

Prolonged cholestatic jaundice with very high bilirubin level due to hepatitis e infection

A 12 year old male child presented with jaundice, generalized itching and disturbed sleep of one and half months duration. Extremely high Serum bilirubin levels (total 38.3 mg/dl, direct 27mg/dl, and indirect 11mg/dl) with normal liver enzymes were documented, which gradually resolved over next two months on supportive management. Hepatitis E infection was diagnosed based on presence of positive Anti hepatitis E IgM antibodies. Underlying associated hepatobiliary diseases were ruled out on a detailed work-up of the case. This case is a unique example of prolonged cholestatic jaundice with extremely high levels of bilirubin with normal liver enzymes in a case of hepatitis E, which has not been reported previously in pediatric age group.

Prolonged Cholestatic Jaundice Associated With Flurbiprofen

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed drugs throughout the world for pain relief. Although the adverse effects of NSAIDs to the liver are well known, flurbiprofen-induced liver cholestasis is extremely rare. Herein, we present a patient with prolonged icterus that is associated with the use of flurbiprofen without causing ductopenia.

Prenatal-Onset Niemann–Pick Type C Disease with Nonimmune Hydrops Fetalis

Niemann-Pick type C (NPC; OMIM 257219) disease is a neurodegenerative lysosomal storage disorder characterized by accumulation of unesterified cholesterol in the lysosomal/late endosomal system. This autosomal recessive disorder occurs in approximately 1/150,000 births. The broad clinical spectrum ranges from a prenatal severe presentation to an adult-onset chronic neurodegenerative disease. Data about prenatal presentation of NPC are limited. A female newborn was born at 34(2) weeks' gestation with a birth weight of 3070 g, and transferred to the Neonatal Intensive Care Unit because of nonimmune hydrops fetalis (NIHF) and respiratory distress. On admission, a physical examination revealed skin edema, mild respiratory distress, and abdominal distention due to massive ascites. Hepatosplenomegaly and cholestasis increased progressively and bleeding diathesis occurred. Results of an abdominal ultrasonography showed hepatosplenomegaly and segmental multicystic dysplastic left kidney. Foamy cells with a lysosomal phospholipid storage pattern compatible with NPC were found in the bone marrow smear. Cultured fibroblasts showed a strongly elevated filipin staining (classical NPC cellular phenotype), establishing the diagnosis of NPC. The infant died on the 52(nd) day of life because of respiratory distress due to lung involvement of NPC, massive ascites, and progressive liver failure. Results of an autopsy showed multiorgan storage disease involving the liver, spleen, lymph nodes, thymus, lungs, and brain. Here, we present a preterm infant with NIHF as a sign of severe prenatal-onset NPC and review the literature.

Ultrasonographic Triangular Cord Sign and Gallbladder Abnormality in Diagnosis of Biliary Atresia

Introduction: Early diagnosis of biliary atresia is very important for better outcome of treatment. Ultrasonography is one of the diagnostic tools for early differentiation of biliary atresia from other causes of neonatal cholestasis. It has been reported that triangular cord sign (TACS) in sonography is a reliable sign for diagnosis of biliary atresia. The aim of this study was to re-assess the accuracy of TACS alone and coupled with an abnormal gallbladder in the diagnosis of biliary atresia. Methods: Infants with prolonged cholestatic jaundice underwent ultrasonography and liver biopsy. Results of ultrasound scans (TASC and gallbladder abnormality) were compared with histopathological findings. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of Ultrasonographic findings for diagnosis of biliary atresia based on liver histopathology were studied. Results: The sensitivity, specificity and accuracy of TACS for diagnosis of biliary atresia were 36%, 95% and 77% respectively. Positive predictive value and negative predictive value was 77%. The sensitivity and specificity of gallbladder abnormality for diagnosis of biliary atresia were 36% and 88% respectively. Positive predictive value of TACS coupled with gallbladder abnormality for diagnosis of biliary atresia was 100%. Conclusion: The Ultrasonographic TACS is very specific for diagnosis of biliary atresia. Positive predictive value and accuracy of this sign is much higher than of gallbladder abnormality. The sensitivity of TACS for diagnosis of biliary atresia is very low.

Transient carnitine transport defect with cholestatic jaundice: report of one case in a premature baby

Carnitine (β-hydroxy-γ-trimethylaminobutyric acid) is involved in the transport of long-chain fatty acids into the mitochondrial matrix and the removal of potentially toxic acylcarnitine esters. Transient carnitine transport defect is a rare condition in newborns reported in 1/90,000 live births. In this paper, we describe a case of transient carnitine transport defect found in a premature baby who had prolonged cholestatic jaundice and poor weight gain, and who responded dramatically to oral carnitine supplementation.