Morning Report

Molly Montes MD PGY2

May 10, 2013

2mo ex-36week preemie female presents with jaundice and abnormal lab values Family member noted yellow skin 2 wks PTA Feeding well 3-4oz Neosure Q3H PO very green stools 4-5x/day Seen by PCP for 2mos WCC Conjugated bilirubin 2.7 CMP notable for

Hyperkalemia - K 6.1 metabolic acidosis - CO2 18 BUN 32 Cr 0.68 Alk Phos 558 ALT 251 AST 264

Presentation

? Echogenic bowel on fetal ultrasound Born vaginally at 36wks for pre-eclampsia BW 1932g NICU stay x5-6days for feeding/growing normal bilirubin at discharge No meds No allergies Mom, Aunt, MGM with splenomegaly and progressive vision loss Brother with large liver New pet dog at home No smoke exposure

History

T-afebrile HR 136 BP 79/36 RR 42 SaO2 >94% in RA Petite, jaundiced infant in no acute distress NCAT, AFOFS, triangular chin red reflex present bilaterally, mild scleral icterus TMs clear, MMM, normal palate No neck masses or LAD Lungs clear, normal WOB RRR, no murmur, normal pulses Liver 1cm BCM, no splenomegaly No sacral dimple or tuft Normal GU exam Green-pale colored stool in diaper Normal extremities/digits Moves all limbs, normal tone and behavior

Physical Exam

Neonatal Hepatitis
AKA Neonatal Cholestasis

Structural Defects

Metabolic

Biliary Atresia Choledochal cysts Alagille syndrome Caroli Disease Congenital hepatic fibrosis Neonatal sclerosing cholangitis Bile Acid Synthesis/Transport Disorder

CF, Wilsons Dubin-Johnson PFIC Polycystic liver/kidney disease

Tyrosinemia Galactosemia Lipid Metabolism disorders Mitochondrial disorders Neonatal Citrullinemia A1AT Deficiency Peroxisomal disorders Urea cycle disorders

Idiopathic

Toxic

Infectious

TPN-induced Drugs

Endocrinopathies

Hypothyroid Hypopituitarism

sepsis Congenital syphilis Echovirus, CMV, EBV Rarely Hepatitis A/B/C toxoplasmosis

Differential

CMP

Hyperkalemia Metabolic acidosis: bicarb 16 Decreased renal function: BUN 26 Cr 0.73 Elevated LFTs: ALT 251, AST 264 Elevated Alk Phos 454

GGT 1164
Urine Studies

UA with micro WNL Urine culture NG Urine succinylacetone normal (test for tyrosinemia)

CBC with differential WNL Coagulation studies WNL

Work-Up

Abdominal Ultrasound

Normal liver Tubular gallbladder Common bile duct not visualized No dilation of intrahepatic bile ducts Mild b/l pelviectasis Kidneys borderline small Normal size and position of spleen Normal hepatic Doppler

Work-Up Imaging

Brother with Hepatomegaly

Diagnosed with A1AT deficiency at age 2

Patients A1AT 38 (normal 100-200), ZZ phenotype

A1AT is antiprotease Deficiency leads to accumulation of often abnormal proteins Lung disease arises from increased amount of elastase which degrades elastin in lung parenchyma leading to emphysema Liver disease attributed to accumulation of abnormal A1AT in hepatocytes Skin findings include panniculitis, urticaria Associated with vasculitis and IBD Occasionally associated with glomerulonephritis and IgA nephropathy 1 in 2000-5000

Alpha-1 Antitrypsin

Progressive destruction and obliteration of extrahepatic biliary tree Unknown Etiology

Abnormal Fetal development

Splenic anomalies

Obstructive cholangiopathy Viral infections Abnormal immune response

Findings cholestasis, HSM, acholic stools May have absent or irregular gallbladder on U/S Treat early with Kasai

Biliary Atresia

Portoenterostomy Roux-en-Y loop of jejunum used to drain bile either from patent common bile duct or directly from liver Delays progression of cirrhosis , portal HTN, and liver failure Risk of cholangitis

Childrennetwork.org

Kasai Procedure

Autosomal Dominant Mutation of Jagged 1 gene on 20p12 Paucity of intrahepatic bile ducts with syndromic features Facies deep set eyes, mild hypertelorism, overhanging forehead, long flat nose, small pointed chin MSK short stature, butterfly or fused vertebrae, rib anomalies, spina bifida occulta Cardiac PPS, TOF, VSD, ASD, Coarct, PA Renal renal artery stenosis, tubulopathies High pitched cry, microcolon, pancreatic insufficiency, multiple ophthalmologic anomalies

Alagille Syndrome

H&P Family History Exposures infectious, idiopathic

LFTs

Transaminitis => Primary hepatocellular injury

GGT and alkaline phosphatase

Biliary tract injury Metabolic liver disease Urine/serum amino acids Urine for succinylacetone Serum iron and ferritin AFP

Coagulation studies

Stool assessment
Micro

Metabolic screen

Blood and urine cultures Viral studies

Laboratory

Fractionated bilirubin

(conj bili >20% total or >2mg/dL)

Bile acids in urine/serum Thyroid studies CF test A1AT level and phenotype

Neonatal Hepatitis Work-Up

Abdominal Ultrasound

Liver size and composition Gallbladder and biliary system Ascites, portal venous flow, spleen

HIDA Scan Hepatobiliary scintigraphy

Radioactive tracer injected into vein Tracer circulates to liver and gets excreted by biliary system and taken into the gallbladder

Cholangiography

Percutaneous transhepatic or via ex-lap Injection of contrast into GB or CBD

MR cholangiography

No radiation exposure

Liver Biopsy

Neonatal Hepatitis Imaging

Cholestasis Retention/Regurgitation Progressive biliary cirrhosis Reduced bile delivery to gut

Decreased luminal bile salts Malabsorption

Portal HTN
Bile acid Cholesterol Bilirubin Pruritis Hepatotoxicity Xanthomatosis Jaundice

Diarrhea

Calcium deficiency

Malnutrition Growth Retardation

Fat-soluble vitamin deficiency A Night blindness D metabolic bone disease K hypoprothobinemia E neuromuscular degeneration

Complications

Treat underlying illness

Ascites

Nutritional support

Growth monitoring Supplemental feeding/TPN MCT, fatty acids ADEK

Diuretics Sodium restriction Paracentesis

Portal HTN with varices

Pruritis

Ursodeoxycholic acid Anti-histamines Rifampin Cholestyramine Phenobarbital

Propanolol, octreotide Endoscopy TIPS

Liver transplant

Management

Patient seen by genetics and nephrology Started on actigall for improved bile flow Started on sodium bicitrate to manage metabolic acidosis 2wks later in clinic

Still vigorously feeding/stooling Increase in HSM Stable LFTs, GGT Low vitamins A&D Started on ADEK Nutritional supplement

Follow-Up

UptoDate. Neonatal Hepatitis Neonatal Cholestasis Nelson Textbook of Pediatrics, 19th ed. Kliegman et al. 1281-1388. e1 2011. Wyllie, Robert and Jeffrey Hyams. Pediatric Gastrointestinal and Liver Disease 3rd ed. 2006. Donia et al. Predictive value of assessment of different modalities in the diagnosis of infantile cholestasis. J Internal Medicine Research. 2010;38(6):2100-16).

References