and metabolic derangements In patients with grade I or II encephalopathy, enteral feeding should be initiated early. Parenteral nutrition should be used only if enteral feeding is contraindicated as it increases the risk of infection. Severe restriction of protein is not beneficial; 60 g/day of protein is generally reasonable. Fluid replacement with colloid (e.g. albumin) is preferred rather than crystalloid (e.g. saline); all solutions should contain dextrose to maintain euglycemia. Multiple electrolyte abnormalities are common in ALF. Correction of hypokalemia is essential as hypokalemia increases the kidneys' ammonia production, potentially exacerbating encephalopathy. Hypophosphatemia is especially common in patients with acetaminophen-induced ALF and in those with intact renal function. Hypoglycemia occurs in many patients with ALF and is often due to depletion of hepatic glycogen stores and impaired gluconeogenesis. Plasma glucose concentration should be monitored and hypertonic glucose administered as needed. Infection Bacterial and fungal infections are common in ALF, with one study demonstrating culture-proven infection in 80% of ALF patients. Defective cellular and humoral immunity as well as presence of indwelling catheters, coma, broad-spectrum antibiotics, and medications that suppress immunity all predispose to infection. Localizing symptoms of infection such as fever and sputum production are frequently absent and the only clues to an underlying infectious process may be worsening of encephalopathy or renal function. There must be a low threshold for obtaining frequent cultures (blood, urine, and sputum), chest radiographs, and paracentesis. Bacteria that enter through the skin, such as streptococci and staphylococci, tend to predominate. Aggressive surveillance is essential as prophylactic antibiotics have shown little benefit. Fungal infections, particularly in the setting of broad-spectrum antibiotics, are also common, and disseminated fungemia is a poor prognostic sign. Liver transplantation The advent of transplantation has changed survival from as low as 15% in the pretransplant era to more than 60% today. Liver transplantation is indicated for many patients with ALF, and survival rates of 56–90% can be achieved. In addition to transplantation, better critical care and the trend toward more benign causes, such as acetaminophen, all contribute to improved survival rates. Spontaneous survival is now around 40%. The application of transplantation among patients with ALF remains low, suggesting that the full potential of this modality may not be realized. Timely availability of an allograft is one of the major factors determining transplant outcomes. In the largest U.S. study, only 29% of patients received a liver graft, while 10% of the overall