Case Presentation: A 25-year-old man presented with two days of malaise, anorexia, nausea, subjective fever and yellowing of his eyes. He denied travel out of the country, IV drug use, and drank alcohol sparingly. Vitals were normal. Physical exam revealed scleral icterus, jaundice, and a normal abdominal and mental status exam. Labs revealed an AST of 3600 U/L, ALT of 4800 U/L, Total bilirubin of 16.0 mg/dL, and INR of 2.0. The white blood cell count was normal. Ethanol, Acetaminophen, or illicit drugs were not detected. A viral hepatitis panel was notable for: positive Hepatitis B surface antigen, positive core antibody, negative surface antibody. Hepatitis B viral load was 170,000,000 IU/mL. Hepatitis B e-antigen and Hepatitis Delta antigen were also detected. Hepatitis A or C antibodies were not detected. The patient was given N-acetylcysteine and Entecavir. By hospital day three, his total bilirubin had increased to 22.0 mg/dL and INR had increased to 8.7 prompting transfer to the ICU. By hospital day 4, the patient became encephalopathic, alert and oriented only to self, and not following commands. CT of the head was negative for cerebral edema. The patient was intubated and given Hypertonic Saline plus Mannitol. The patient was listed for liver transplant at 1A status for Fulminant Hepatic Failure secondary to acute Hepatitis B. On hospital day 5, the patient underwent orthotopic liver transplantation. Hepatitis B immune globulin was given. The patient was discharged home on hospital day 14.
Discussion: Acute Liver Injury is commonly encountered in Hospital Medicine. The most common etiologies of acute liver injury include drug induced liver injury and acute viral hepatitis. During acute Hepatitis B infection, approximately 70% of patients have subclinical hepatitis and around 30% have icteric hepatitis. Acute Liver Failure is uncommon in acute Hepatitis B, occurring in 0.1-0.5% of patients, and thought to be secondary to the immune-mediated lysis of Hepatocytes. Acute Liver Failure is diagnosed by fulfilling three criteria: 1) Elevated Aminotransferases 2) Hepatic Encephalopathy 3) Prolonged Prothrombin Time (INR >1.5). The factors increasing the risk of Acute Liver Failure include the use of Acetaminophen or Ethanol and co-infection with Hepatitis D, which was noted in this patient. Treatment of Acute Liver Failure includes ensuring the patient is managed at a hospital with transplant capabilities. Also, patients with grade III or IV encephalopathy should be in the ICU. Lactulose given for hepatic encephalopathy in this setting has not been shown to improve outcomes and may actually cause bowel distention that can technically complicate Liver transplantation. Cerebral edema is the primary cause of death in Acute Liver Failure. Hypertonic saline is given to patients at a higher risk of increased intracranial pressure. Overall survival rates for Acute Liver Failure are >60%, and 55% of patients will survive without needing a transplant. After transplant, the one-year survival rate is 80%.
Conclusions: The majority of patients with acute Hepatitis B infection will be asymptomatic. Only a very small minority will progress to Fulminant Hepatic Failure. Patients hospitalized with acute Hepatitis B infection often appear clinically well despite their abnormal liver function tests. For Hospitalists caring for patients with Acute Liver Injury, close monitoring for deterioration in mental status is key in order to diagnose Acute Liver Failure which can ultimately be fatal.