Jaundice in Children Abdulwahab Telmesani FRCPC,FFAP Faculty of Medicine and Medical Science Umm Al-Qura University

An Approach to a Child With Direct Hyperbilirubinemia

Classic Approach Proper detailed history Proper physical examination Formalize an impression of prioritized DDx Appropriate investigations

Identify Acute Chronic (more than 6 months)

In Children Acute Chronic (more than 6 months)

Identify Hepatocellular Chlestatic

In Children Hepatocellular (ALT/AST more than twice of ALP) Cholestatic (ALT/AST less than twice of ALP)

Remember The prognostic value of Albumin Coagulation profile

Etiology Infection Drugs Specific Entities Vascular

Etiology Infection Drugs Specific Entities Vascular

Infections Viral Bacterial Parasitic

Viral Hepatitis Hepatotropic Virus’s (replicate in the liver and causes hepatitis) Others

Hepatotropic Viruses HBV (10-20% Chronic active hepatitis) HCV (70-80% Chronic active hepatitis)

Hepatotropic Viruses Non B / C Viral Hepatitis HAV HEV HFV HGV TTV SEN

Others EBV CMV Herpes Other

Hepatitis A Virus Most common cause of community acquired hepatitis through out the world

Hepatitis A Virus RNA Picorna Virus (Rhinovirus, Enterovirus, Cocxackievirus) Feco - oral transmission (Food – borne +/- Water – borne) Day care centers account for 10% of cases

Hepatitis A Virus Transmission in 50% of contacts

Hepatitis A Virus Liver injury in HAV is secondary to immune response not to cytopathy

Hepatitis A Virus Presentation Incubation period 4 weeks Prodrome 1 week Jaundice 1 – 3 weeks Hepatomegaly Liver enzymes 20 – 100 time upper normal Spontaneous resolution

Hepatitis A Virus Presentation Sporadic Epidemic Endemic

Geographic Distribution of HAV Infection

Hepatitis A Virus Clinical Presentation in Endemic areas 10 % of children below 6 years 40 % of children 6 – 14 years 70 % of subjects older than 14 years 70 – 100 % of children have been infected

Hepatitis A Virus Epidemic Tend to seasonal Symptoms as in sporadic cases

Hepatitis A Virus No Chronic Sequelae

Hepatitis A Virus Variants Relapsing course up to 1 year Cholestatic up to 2 years Immune-complex features ( vasculitis, arthritis…)

Hepatitis A Virus Fatalities Secondary to acute hepatic failure Less than 2 % More in older children and adults When on top of chronic hepatitis

Hepatitis A Virus In Shanghais HVA epidemic, mortality was 5 times higher among patients with chronic hepatitis B

Hepatitis A Virus Prevention Immunoglobulin Vaccination ( 2 doses 6 months apart above 1 year of age)

Hepatitis A Virus ? Atopy protect against enteric infection including HAV P N Black Allergy 2005

Hepatitis B Virus Vaccination decreased the incidence of hepatic carcinoma in children (in adults in future)

Hepatitis C Virus Perinatal transmission about 6% Elective C/S might lower the risk No evidence of risk of breast feeding

Hepatitis E Virus Single Strand RNA Feco – oral transmission Endemic in Tropical and Subtropical countries Mortalities 0.2 % but as high as 4 % in pregnant women

Hepatitis E Virus Incubation period 2 – 9 weeks Presentation similar to Hepatitis A Diagnosed by Anti HEV IGM serology No chronic sequelae reported It worsens chronic hepatitis No vaccine available yet

Hepatitis G Virus Enveloped RNA virus Parental transmission Detected by PCR 2-39% of non A-E hepatitis 16-43% of Fulminant hepatitis ? Hepatotropic No established serology

TTV Single strand DNA Isolated from patients post transfusion (100 %) Isolated from patients with non A-E Hepatitis Presents in health individuals 1 – 13% (89 %) ? Feco – oral transmission ? Normal human viral flora

SEN Virus Single strand DNA virus Most recent cause of non A- E Hepatitis Found in Blood donors 1- 13% In 70% of transfused patients ? Hepatotropic ? Feco – oral transmission.

Etiology Infection Drugs Specific Entities Vascular

Paracetamol Commonest cause of acute liver failure in USA We all have it at home Toxic dose is more than 150 mg /Kg

Paracetamol Need repeated serum drug level Follow Rumack-Matthew nomogram A point of irreversible liver damage (end stage liver disease) N-cetylcysteine is the anti-dote (oral/intravenous) Liver transplant when end stage liver disease

Etiology Infection Drugs Specific Entities Vascular

Specific Entities Wilson’s Disease A1 Antitrypsin deficiency IBD Hepatitis Auto-immune Hepatitis Syndromatic Diseases Metabolic Progressive Familial Intrahepatic Cholestasis

Wilson’s Disease Autosomal Recessive Disease Low cerulplasmin Copper deposition in; liver, brain, kidneys, eyes, heart, Hemolysis

Wilson’s Disease Presents in any of the following; Acute liver disease Chronic liver disease Minimal neurological manifestations Sever neurological manifestations Psychiatric symptoms Renal tubular acidosis Bony deformities Hemolytic anemia

Wilson’s Disease An 18 years old male and 19 years female reported with Schizophrenic symptoms; No Kayser -Fleischer ring Normal physical examination Low cerulplasmin, high serum copper and high 24 HR urine copper Symptoms improved on D – Penicillamine Patrick Stiller J Psych. Neurosci 2002

Wilson’s Disease Liver biopsy and determination of hepatic copper is the golden standard for diagnosis of Wilson’s Disease

Wilson’s Disease Diagnosis can be made based on at least two of the following ; Low serum Cerulplasmin High 24 HR urine copper K.F Ring Ashish Bavdekar J Gastr & Hepat 2004

Wilson’s Disease Treatment; D- Penicillamine Trientine Zinc

Etiology Infection Drugs Specific Entities Vascular

Sickle cell Disease Budd - Chiari Syndrome Constrictive Pericarditis Veno - occlusive disease seen with chemotherapy