Itching and malaise for one month

The patient is a 33 year old Hispanic woman admitted through the JHU Emergency Department with one month of itching, malaise, occasional fever and chills, and markedly elevated serum transaminases. She was in good health prior to the development of nausea and jaundice approximately 3-4 weeks previously. Within the week before she reported malaise and a 'flu-like' feeling including subjective fevers. Evaluation by her physician revealed abnormal liver function tests including total bilirubin 6.9, AST 1524, ALT 2883, alk phos 177. She had no history of abnormal liver function abnormalities. Her transaminases and bilirubin levels continued to increase, and a percutaneous liver biopsy was deferred due to a simultaneously increasing INR. She was sent to JHH for further evaluation and treatment.

There was no history of mental status or cognitive changes. She did report worsening malaise and fatigue. Her temperatures were low grade and episodic with no rigors. She had received no antibiotics over the prior month and did not take anti-pyretics.

Ten months prior to admission she had an uncomplicated vaginal delivery of a normal child with epidural anesthesia. There is no history of blood transfusions, IV drug use, ethanol abuse, or HIV risk behavior. She has no family history of liver disease. She has not traveled overseas in the past 2 years.

None except for childbirth 10 months previously. No surgical history.

Negative for history of liver disease, autoimmune, infectious diseases.

Has an occasional alcoholic beverage. Denies smoking and illicit drug use. Patient has 2 tattoos, received 5 and 10 years previous. Prior to having her child, she worked in a sporting goods store with no occupational exposure to chemicals. She has been a full-time mother since childbirth 10 months previous. Her child is healthy. She was born in Honduras. Her parents brought her to the US at age 2. They now live in Massachusetts which she visits periodically.

Over the counter multivitamin. No acetaminophen, non-steroidals, herbals or other supplements.

No known drug allergies.

HEENT: patient describes scleral icterus.
GI: patient has had light-colored stools, but denies any other change in bowel habits.
GU: Dark urine.
Hematologic: No history of bleeding or clotting difficulties.

• VS: T=99.4, HR=84, RR=16, BP=122/68
• General: well-developed, well-nourished female in no apparent distress.
• HEENT: Scleral icterus.
• Neck: Soft, supple, no lymphadenopathy.
• CV: RRR
• Lungs: Clear to auscultation bilaterally.
• Abdomen: Flat and non-tender. Normal bowel sounds.
• Extremities: No edema is present.
• Neurologic: cranial nerves II-XII grossly intact. No asterixis is present.

• Na 139; K 3.8; Cl 106; BUN 7; Cr 0.6; Glucose 112; Calcium 8.8; TP 5.7; Albumin 3.3; TBili 34.9; direct bili 18.9; AST 5169; ALT 2892; Alk Phos 196
• WBC 8360; RBC 4.46 ; Hemoglobin 12.9; Hct 31.8; MCV 28.5 ; Platelet 281,000
• INR 2.0, PTT ratio 1.6, PT 17.8
• TSH 1.9
• Troponin less than 0.6
• Acetaminophen level less than 30
• Ammonia 51
• Urine drug screen negative
• Hepatitis B surface antigen negative; anti-hepatitis B core antigen IgG and IgM negative; anti-hepatitis A IgM, negative. Hepatitis C PCR negative. VZV IgM and IgG positive, however VZV and CMV culture negative.

The hepatic artery, inferior vena cava, hepatic veins and portal veins are patent with appropriate wave forms and direction of flow.

Figure 1: Arterial phase. Arteries are patient.
Figure 2: Venous phase. Portal vein patent. Mild periportal edema (arrows). Diffuse heterogenous enhancement, nonspecific.
Figure 3: Venous phase. Patent hepatic veins.

The patient was admitted to the Medical Service for further evaluation. The AST and ALT began falling and the bilirubin and INR began to rise slowly. Lactulose was administered. Approximately 5-6 days after admission (six weeks after her initial presentation) the patient developed mild confusion and somnolence. Physical examination revealed asterixis. She was transferred to the MICU. Over the next two days mechanical ventilation was initiated, she became comatose despite lactulose and grew E. coli from her urine. She subsequently developed hypernatremia, metabolic acidosis, coagulopathy, and hypotension. Blood and urine cultures remained negative on antibiotics. She was listed for a cadeveric liver transplant. Due to suspected elevated pressures, a subdural intracranial pressure monitor was placed. The patient was managed with IV mannitol with subsequent normalization of her intracranial pressure. The patient later became progressively hypotensive and her intracranial pressure began to rise again. The patient was again treated with mannitol and hyperventilation. The apparent intracranial pressure fell after this treatment. However, the patient developed evidence of pupillary abnormalities as well as seizure movements involving her left face and neck. A CT scan was performed showing cerebellar tonsillar herniation and findings consistent with diffuse edema. The patient's neurological status continued to deteriorate and in light of her very poor prognosis, ultimately a decision to withdraw care was made. She expired 12 days after admission.

What is the likely cause of the patients liver failure?
What diagnostic tests would be useful?
What is the most likely cause of death?