Barath Jagadisan

Acute on chronic liver disease in children from the developing world: recognition and prognosis.

Objectives: A subset of children with chronic liver disease (CLD) decompensate following an acute insult; however, data for children are not readily available. The present study aims to characterize the clinical presentation, etiology, outcome, and determinants of short-term mortality in children with an acute hepatic insult superimposed over CLD. Patients and Methods: Children of acute on chronic liver disease (ACLD) were grouped as acute on chronic liver failure (ACLF) and non-ACLF. ACLF was defined as per the definition proposed by Asian Pacific Association for the Study of Liver. The acute insult, etiology of CLD, and clinical and laboratory parameters at admission along with 3-month outcome were assessed. Receiver operating curve (ROC) was plotted to measure the performance of pediatric end-stage liver disease (PELD) score in predicting the 3-month mortality. Results: Of the 36 children with ACLD (median age 9.5; range 3–15 years), 17 fulfilled ACLF criteria and 19 non-ACLF. CLD was diagnosed for the first time in 86% children during their presentation with a superimposed acute insult. Wilson disease and autoimmune liver disease were the most common underlying etiology. Acute insult was caused by hepatitis E virus (HEV) in 27 (75%) children and hepatitis A virus (HAV) in 10 (28%). The 3-month mortality of ACLF group was significantly higher than that of non-ACLF group (59% vs 11%, P = 0.001). PELD score of >25.5 predicted death, with a sensitivity of 100% and specificity of 83.3%. Conclusions: Superinfection with hepatotropic viruses on CLD in children manifests as ACLD: ACLF and non-ACLF. Hepatitis E virus is the most common superinfection in the population studied. The mortality in ACLF is 5 times higher than that in the non-ACLF group. PELD score is useful in differentiating likely survivors and nonsurvivors.

Child with Jaundice and Pruritus: How to Evaluate?

Jaundice with pruritus is a manifestation of cholestasis. The defective biliary drainage causes accumulation of substances that are usually excreted in bile, which in turn causes pruritus. The exact nature of the pruritogen is under evaluation. However, lysophosphatidic acid is the current favourite. The causes of cholestasis can be broadly classified as intra or extrahepatic, with intrahepatic disorders being more often associated with pruritus. Cholestatic phase of acute viral hepatitis, progressive familial intrahepatic cholestasis, syndromic and non-syndromic paucity of intralobular bile ductules, drug induced cholestasis and sclerosing cholangitis (SC) are the common causes in children. An algorithmic approach facilitates early etiological diagnosis by careful clinical evaluation combined with investigations including gamma glutamyl transpeptidase, radiological imaging (ultrasonography, magnetic resonance cholangiopancreatography), liver biopsy and genetic analysis. Management is largely supportive and includes nutritional rehabilitation with supplement of fat soluble vitamins and calcium, stepwise therapy of pruritus with drugs (ursodeoxycholic acid, rifampicin, bile acid sequestrants and/or opioid antagonists) and biliary diversion surgery. Complications of advanced liver disease and portal hypertension need to be addressed. Liver transplantation is required in children with refractory pruritus affecting the quality of life or those with end stage liver disease. Relief of biliary obstruction by endoscopy or surgery and treatment of diseases associated with SC like histiocytosis may be rewarding. Long-term follow-up for development of complications of liver disease and hepatocellular/ cholangiocarcinoma is essential. Thus, an early diagnosis and stepwise treatment with an understanding of the pathogenesis of pruritus in cholestatic disorders may decrease morbidity and mortality.

Propofol-ketamine and propofol-fentanyl combinations for nonanesthetist-administered sedation.

Objectives: There is a need to compare propofol requirement between propofol-ketamine (PK) and propofol-fentanyl (PF) given as nonanesthetist-administered propofol sedation during pediatric esophagogastroduodenoscopy (EGD). Methods: The study was a parallel-group, randomized, double-blind comparison of the need for additional doses of propofol in the first minute after sedation induction between PK and PF, administered by rotating trainees in pediatrics for sedation during pediatric EGD. A total of 95 children with American Society of Anesthesiologists class I to III between 3 and 12 years undergoing EGD were included and randomized to either of the groups. After midazolam premedication, children received either 0.5 mg/kg ketamine (PK) or 1 &mgr;g/kg of fentanyl (PF) followed by a mandatory 1 mg/kg of propofol. Additional doses of propofol of 0.5 mg/kg each were given to achieve sedation induction (modified Ramsay scale level 6), and further doses were administered during the procedure as required. A total of 92 children (PK, n = 47; PF, n = 45) were analyzed. P < 0.05 was considered significant. Results: There was no difference in the propofol dose required for successful scope introduction and also in the need for additional propofol doses and the total additional propofol doses required in the first minute after sedation induction. Propofol injection pain was higher in the PF group (odds ratio 1.78). The adverse events and recovery time were similar. There was no escalation of care, airway intubations, death, or disability. Conclusions: Nonanesthetist-administered propofol sedation is feasible in teaching hospitals. Propofol requirement is similar in both PK and PF combination regimens, but the lower frequency of propofol injection pain may favor the use of PK.

Referral Patterns and Factors Influencing Age at Admission of Infants with Cholestasis in India

ObjectivesTo define the recognition, age at admission, referral time and referral pattern of neonatal cholestasis in India.MethodsThis prospective, observational study was conducted from February 2015 through March 2016 in the Pediatric gastroenterology unit of JIPMER, Pondicherry in infants with cholestasis < 6 mo of age.ResultsAmong 64 infants, median age of admission was 52 d (IQR 28–63 d). Fifty of sixty four infants (78.1%) came with parent-reported cholestasis-related symptoms of either jaundice alone (57.8%) or bleeding manifestations (20.3%). In 21.9% infants, jaundice was detected by physicians at a median age of 45 d (IQR 38.5–53.2 d). Two infants had intracranial bleed. Only 34% infants with pale stools were identified by the mother. The median healthcare-seeking time was 5.5 d (IQR 2.5–12 d). Among infants presenting to primary healthcare physicians (PHPs) with cholestasis-related symptoms, median time to referral was 5 d (IQR 2.5–12 d). The first point of healthcare contact in 54.7% was a PHP; 17.1% PHPs had reassured the parents. Herbal preparations were prescribed by 14.3%. Only 11.8% of those with jaundice as the only problem were given vitamin K before referral. Biliary atresia (BA) was missed in neonatal intensive care units in 9 cases.ConclusionsThe above issues need to be accounted for before evaluating or implementing screening strategies in India.

Wilson disease and lupus nephritis: is it coincidence or a true association?

Abstract A 12-year-old girl born to third-degree consanguineous parents presented with recurrent episodes of haematuria for 8 months in association with peri-orbital and lower limb oedema for 20 days. There was no jaundice, hepatomegaly or neurological abnormality at presentation. An older brother had died following jaundice at 10 years of age. Urinalysis showed multiple dysmorphic erythrocytes without proteinuria and there was leucopenia, thrombocytopenia and hypo-albuminaemia (23 g/L). C3 component of complementaemia was low and anti-nuclear antibodies and anti-double-stranded DNA antibodies were strongly positive by immunofluorescence. Systemic lupus erythematosus (SLE) was considered but the severe hypo-albuminaemia was unexplained. During the pre-renal biopsy work-up, a deranged coagulation profile with raised transaminases prompted evaluation for chronic liver disease which culminated in the diagnosis of Wilson disease. Treatment with penicillamine and immunosuppressants was initiated, but there was neurological deterioration on Day 30 of admission and she died owing to worsening liver failure on the Day 41. Post-mortem liver biopsy demonstrated cirrhosis and post-mortem renal biopsy showed features of class-II lupus nephritis. Auto-immune antibodies and autoimmune disorders have been reported in Wilson disease and there are anecdotal reports of an association of SLE with Wilson disease. However, this case is unique in that lupus nephritis was the presenting manifestation before Wilson disease was diagnosed. The underlying pathophysiological mechanisms of this association requires further research.

Acute Motor Axonal Polyneuropathy Following Mumps Infection in a 9-Year-Old Girl

A 9-year-old girl presented with lower motor neuron type of paralysis involving limbs, trunk and multiple cranial nerves (7, 9 and 10) with preceding history of mumps 1 week before the onset of weakness. There were no features to suggest either a meningitis or encephalitis in the child. Cerebrospinal fluid showed hypoglycorrhachia and mild protein elevation; magnetic resonance imaging of the brain was normal. Nerve conduction study showed motor axonal neuropathy. Serology for mumps IgM was positive, consistent with a diagnosis of post-mumps acute motor axonal polyneuropathy. The girl made a complete recovery within 3 weeks.

Validation of Adapted Dartmouth Operative Conditions Scale for sedation during pediatric esophagogastroduodenoscopy

Pediatric esophagogastroduodenoscopy requires deep sedation as it involves stimulation of the airway. Frequency of adverse events is higher with esophagogastroduodenoscopy. Hence, monitoring needs sedation scales like the Dartmouth Operative Condition Scale that identifies safe states of sedation. This study aims at validating the Adapted Dartmouth Operative Condition Scale for sedation rating by pediatricians during pediatric esophagogastroduodenoscopy.

Chronic Pruritus in an 18-Month-Old Male Infant Due to Anicteric Cholestasis

An 18-month-old male infant was referred to us with pruritus from 6 months of age. He was being managed as atopic eczema with emollients and antihistamines without any response to treatment. On examination, he was found to have extensive scratch marks, mild hepatomegaly and no icterus. Blood investigations were suggestive of anicteric cholestatic liver disease. Liver biopsy was suggestive of progressive familial intrahepatic cholestasis type 3. He showed symptomatic improvement after starting ursodeoxycholic acid and fat-soluble vitamins and is under follow up.

Glycogen storage disease type VI with a novel mutation in PYGL gene

BackgroundGlycogen storage disease type VI (GSD-VI) presents with failure to thrive and also fibrosis in some cases, without cirrhosis.Case characteristics2½-year-old girl presented with short stature, transaminase elevation and significant fibrosis, suggesting GSD-III.ObservationA pathogenic mutation in PYGL gene suggested GSD-VI.MessageGSD-VI should be a differential diagnosis whenever GSD-III is suspected.

Sub-conjunctival Hemorrhage Following a Bout of Cough: A Harbinger of Underlying Bleeding Diathesis

To the Editor:A five-year-old girl presented with red eyes for 15 d following a brief bout of cough illness. There was no pain, itching or watering of eyes or diminution of vision. There was no history of bleeding from any other site and no history of recent trauma. However, there was a history of prolonged bleeding from the umbilical stump in the neonatal period and also following trivial trauma in the past which had been forgotten. She was born out of a non-consanguineous marriage with no family history of bleeding diathesis. Examination revealed bilateral subconjuctival hemorrhage (Fig. 1). Clinical examination was otherwise unremarkable. Investigations revealed Hb of 9.3 g/dl , p la te le t count of 508,000/cu .mm, Prothrombin time (PT): > 240 s (INR >4); activated Partial thromboplastin time (aPTT): > 240 s; Thrombin time (TT): >180 s. Liver function test (LFT) was normal. A diagnosis of congenital fibrinogen deficiency was suspected. Serum fibrinogen level was 29 mg/dl (normal value 200–400 mg/dl). In the hospital she developed prolonged bleeding from the venepuncture sites which subsided with two units of fresh frozen plasma. At two weeks follow-up, the sub conjunctival hemorrhage had completely resolved. Inherited disorders of fibrinogen can either be a type 1 defect comprising afibrinogenemia and hypofibrinogenemia (quantitative deficiency) or a type 2 defect comprising dysfibrinogenemia (qualitative defect) [1]. Afibrinogenemia is inherited as an autosomal recessive condition presenting as umbilical cord bleeding, cutaneous, gastrointestinal and rarely, joint or central nervous system bleeds. Antenatal onset intracranial bleeds and spontaneous splenic rupture have also been reported [2, 3]. These children have prolonged PT, aPTT and TT. Hypofibrinogenemia is transmitted as an autosomal dominant or recessive condition and blood fibrinogen levels are usually above 0.1 g/L. Bleeding manifestations are less severe than afibrinogenemia [1, 4]. Rarely, they may be associated with intraosseous pseudotumors [5]. PT, aPTT and TT are prolonged. In dysfibrinogenemia, fibrinogen levels are usually between 1.5 and 3.5 g/L and thrombosis is more common than hemorrhage [1]. PT and aPTT are normal with prolonged TT. Treatment for all the above