**2.2 Diagnosis and initial management considerations in ALF**

Potential causes of ALF must be actively sought in the initial workup, as certain etiologies have specific life-saving treatments. Acetaminophen toxicity is treated with N-acetylcysteine, autoimmune hepatitis with corticosteroids, herpes simplex and varicella zoster viruses with intravenous acyclovir, acute fatty liver of pregnancy and HELLP syndrome by delivery of the fetus. Recent data suggests that the use of N-acetylcysteine (NAC) improves the outcome of patients with ALF, independent of the etiology (*Lee et al., 2009*). Many transplant centers advocate the use of NAC for all patients with ALF. NAC can be administered intravenously at a dose of 150 mg/kg over 15 minutes followed by 50 mg/kg over 4 hours, followed by 100 mg/kg over 16 hours. Adverse effects of NAC include bronchospasm and anaphylaxis and are managed by coadministration of antihistamines and corticosteroids as well as reduction of infusion rate. Oral preparations of NAC are also available. Discontinuation of NAC is appropriate following resolution of ALF or at the time of transplantation.

In addition to ruling out reversible causes of ALF, exclusion of chronic liver disease is crucial for appropriate management. Physical examination of patients presenting with liver failure should therefore focus on stigmata of chronic liver disease, including abdominal ascites, spider angiomata, or *caput medusae*. Hepatic imaging with ultrasound, CT or MRI is useful to evaluate for the presence of portal hypertension and chronic liver disease, as well as to evaluate hepatic size and vasculature, ascites, and hepatic masses. Recommended laboratory testing for potential etiologies of ALF include autoimmune markers, viral serologies, toxicology screen, and serum and urine testing for copper overload.

### **2.3 Patient stabilization**

All patients with ALF should be monitored and treated in an intensive care unit. Many patients have progressed to multi-organ failure upon arrival, and immediate supportive measures should be undertaken. These may include interventions such as endotracheal intubation and mechanical ventilation, intravenous fluid resuscitation, placement of arterial and central venous lines, and vasoactive agent support.
