Acute liver failure and aplastic anemia in an 11-year-old girl.

An 11-year-old previously healthy female presented with a 1-week history of jaundice and fatigue. Her aspartate aminotransferase (AST) level was 1,420 U/L, alanine aminotransferase (ALT) 1,044 U/L, total bilirubin 16.5 mg/dL and international normalized ratio (INR) for prothrombin time 1.2. Complete blood count showed a white blood count of 7,700/mm, hematocrit 40.6 g/dL, and platelet count 509,000/mm. Ultrasound demonstrated mild hepatomegaly but was otherwise normal. Serology was negative for hepatitis A, B, and C and Epstein-Barr virus (EBV) and cytomegalovirus (CMV). After discharge, she was followed by her outpatient pediatric gastroenterologist, who noted that she continued to have jaundice and elevated aminotransferase levels. A liver biopsy was recommended, but her parents refused, and the patient was lost to followup for several months. Four months after her initial presentation, the patient represented with a 2-week history of sleepiness, headaches, increased jaundice, and anorexia. During the time she was lost to follow-up, her parents noted an initial improvement of her jaundice and energy. However, 2 weeks prior to her readmission, she had increasing fatigue, jaundice, and epistaxis. Complete blood count revealed a WBC of 2.3 g/mm, hematocrit 33.2 g/dL, and platelet count 13,000/mm. Total bilirubin was 21.8 mg/dL, direct bilirubin 14.6 mg/dL, AST 3,158 U/L, ALT 3,239 U/L, INR 2.0, erythrocyte sedimentation rate 16, C-reactive protein 23 mg/dL, and ammonia 38 lm/L. She was admitted for lethargy in the setting of liver failure and pancytopenia. On admission to the hospital, her vital signs were normal and physical examination revealed an alert, interactive female with marked jaundice. Lungs were clear to auscultation, and heart tones were regular with no murmurs. Her abdomen was soft, nontender and not distended; her liver was palpated 2 cm below the right costal margin, and the spleen tip was palpated 3 cm below the left costal margin. Ultrasound of the abdomen showed mild hepatomegaly and thickened gallbladder wall with no sludge or stones. She was listed for liver transplantation, and began transfusion therapy with fresh frozen plasma and platelets as needed for procedures. Further blood tests showed negative human immunodeficiency virus (HIV) antibody, CMV polymerase chain reaction (PCR), and EBV PCR. Her alpha-1-antitrypsin level was normal, anti liver-kidney microsome antibody negative, antismooth muscle antibody negative, antinuclear antibody negative, drug screen for urine and serum negative, varicella immunoglobulin (Ig)G negative with an equivocal IgM. Ophthalmology consultation was negative for ocular abnormalities and Kayser-Fleischer rings, and her serum ceruloplasmin was 29 mg/dL. A 24-h urine collection for copper was 260 mcg/specimen (normal, less than 60), but the reliability of this test was questioned given that the patient had 4 L of urine collected while receiving furosemide. A magnetic resonance cholangiopancreatography (MRCP) showed no biliary stones or biliary dilatation, a mildly enlarged liver and spleen, thickened gallbladder wall, pericholecystic fluid, trace bilateral pleural effusions, and A. M. Yeh D. Bass (&) Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Stanford University Medical Center, Lucile Packard Children’s Hospital at Stanford, 750 Welch Road, Suite 116, Palo Alto, CA 94304-0126, USA e-mail: dmbass@stanford.edu