Case 1 - Click here for Text and References

Submitted by: Kevin E. Bove

Clinical Summary:

A male child born at term after an uneventful pregnancy had no apparent developmental anomalies. The family history was negative. Persistent neonatal direct hyperbilirubinemia gradually subsided with phenobarbitol therapy. Investigations for biliary atresia and alpha-1AT deficiency were negative. Stool color was normal. Primarily breast fed, his subsequent growth was slow and plateaued at 4-6 months. At age 6 months he presented to an ER with acute irritability, and a convulsion. Imaging revealed a small subarachnoid hemorrhage. There was no jaundice.

A liver panel.was normal except for a prolonged prothrombin time (>100 seconds) which rapidly corrected with intravenous vitamin K. The liver was firm at 2 cm below the RCM. Splenomegaly was absent. There was no neurological deficit.

Laboratory values at discharge were ALT 37U/L, conjugated bilirubin 0.4 mg/dl, alkaline phosphatase 354 IU, albumin 3.5gm/dl. The urine organic acid profile, hepatitis serology panel, coagulation factor panel. serum levels of vitamin A, D-25 and E, and serum bile acids were normal. Serum amylase was 17 units (low)

Discharge medications included a vitamin tablet containing vitamins A, D, E, and K, a supplemental Vitamin K tablet, phenobarbitol and MCT oil. At discharge one month after admission, he weighed 6.8 kg and was neurologically intact.

He was referred to a pediatric gastroenterologist at a university center for further investigation. At 8 months of age he was gaining weight, meeting all developmental milestones and was described as alert and vigorous. Laboratory study results were as follows: AST 68 U/L (H), ALT 45 U/L, GGT 70 U/L, bilirubin unconjugated 0.1Mg/dL, bilirubin conjugated 0.1Mg/dL, alkaline phosphatase 646 U/L (H). Additional studies were a sweat test (normal), a liver biopsy and urinary organic acid evaluation.

Case 2 - Click here for Text and References

Submitted by: Milton J. Finegold

Clinical Summary:

Two month old male admitted to hospital for G-tube placement and fundoplication because of failure to thrive ( he weighed 3745 g; length was 57 cm). Shortly after birth at term, hypotonia was evident and seizures began. Dysmorphic features included flat facies, high forehead and inner epicanthal folds. Fontanelles were wide open and there was ventriculomegaly. The left optic nerve was hypoplastic. Karotyping was 46XY with no chromosomal defects. Because of rhinorrhea, cough, and fever, surgery was cancelled and antibiotics given. He was jaundiced with hepatomegaly and lab values included: AST 688, ALT 287, Alk phos 315, GGT 108, Albumin 3.4. He developed respiratory insufficiency, apneic spells and desaturation and died within 48 hours. Autopsy was limited to chest and abdomen: findings included enlarged and firm liver (340 g vs 140 expected), splenomegaly (40 g vs 14), small subcapsular cysts in both kidneys, atrophic thymus and pulmonary congestion, edema and multiple foci of consolidation.

Case 3 - Click here for Text and References

Submitted by: S. Ranganathan

Clinical Summary:

A 3 year old male status post liver transplantation 9 months ago for Ornithine transcarbamylase (OTC) deficiency presents now with jaundice and clay-colored stools. An ultrasound showed no biliary dilatation or evidence of obstruction. His liver enzymes were significant for a total bilirubin of 7.8mg/dl with a direct of 4mg/dL. His SGOT and SGPT were 408 and 311 IU respectively while his GGTP was 376 IU/L with alkaline phosphatase of 217. His enzymes 20 days ago were only minimally elevated with GGTP being normal (21 IU/L). There was only one known episode of acute cellular rejection seen on biopsy at 3 weeks post- transplant which was treated with enzymes normalizing. The child did have episodes of upper respiratory infections intermittently that would be associated with some elevation of liver enzymes usually SGOT/SGPT but no jaundice or hyperbilirubinemia. He has been on Tacrolimus and predisone and is negative for CMV, EBV and hepatitis viruses at the time of biopsy. A representative section of the liver biopsy done 9 months post-transplant for the elevated enzymes and jaundice is submitted for evaluation. Additional images of representative areas and special stains are included. Also images of the immediate prior allograft liver biopsy 3 months earlier(H&E and cytokeratin 7) are included for comparison.

Case 4 - Click here for Text and References

Submitted by: Pierre A. Russo

Clinical Summary:

A full term boy with unrepaired but well compensated Tetralogy of Fallot presented with jaundice at 2 months of life. Diagnostic work-up included an abdominal ultrasound which demonstrated a small gallbladder. Hepatobiliary Iminodiacetic Acid (HIDA) scan was non-excreting. A liver biopsy was performed on day 79 of life (Figure 1). It was decided to explore the child because obstruction could not be ruled out. An intraoperative cholangiogram showed drainage into the duodenum with an intact cystic duct and common bile duct but no visualization of the common hepatic duct or intrahepatic bile ducts. Further operative dissection revealed a completely absent hepatic duct and no evidence of hepatic ducts at the entry to the liver. It was felt that the patient’s biliary anatomy was most consistent with biliary atresia and a hepatoportoenterostomy was performed. Figure 2 is from the fibrous plate and Figure 3 from the wedge liver biopsy performed at the time of the portoenterostomy.

Pertinent Laboratory Data:

Labs at the time of admission were as follows: Total bilirubin 6.4 Conjugated bilirubin 3.1 AST 380 U/L (ref: 5-30 U/L) ALT 176 U/L (ref 5-35 U/L) Alk Phos 755 U/L (ref 70-345 U/L) GGT 525 U/L (ref 9-23 U/L).