Globally, hepatitis A and E infections are probably responsible for the majority of cases of acute liver failure, with rates of death of more than 50% reported from the developing world. Acute liver failure may also occur after hepatitis B infection, which is a common cause in some Asian and Mediterranean countries. Particularly poor survival has been seen in patients with reactivation of previously stable subclinical infection with the hepatitis B virus without established chronic liver disease. This scenario is most common in patients with treatment-induced immunosuppression during or after therapy for cancer. The identification of at-risk patients and the use of antiviral prophylaxis before the initiation of chemotherapy, immunotherapy, or glucocorticoid therapy are effective in prevention. Other rare viral causes of acute liver failure include herpes simplex virus, cytomegalovirus, Epstein–Barr virus, and parvoviruses. 
 
Drug-Induced Liver Injury
Drug-induced liver injury is responsible for approximately 50% of cases of acute liver failure in the United States. Such injury may be dose-dependent and predictable, as exemplified by acetaminophen-induced hepatotoxicity, which is the most common cause of acute liver failure in the United States. It may also be idiosyncratic, unpredictable, and probably independent of dose.

Although acute liver failure after acetaminophen ingestion can occur after consumption of a single large dose, the risk of death is greatest with substantial drug ingestion staggered over hours or days rather than at a single time point. Acute liver failure is more common with late presentation to medical attention because of unintentional rather than deliberate self-poisoning.18 Malnourished patients and patients with alcoholism are at increased risk. Acetaminophen is also a potential cofactor for hepatic injury in patients taking the drug for the relief of symptoms from hepatic illness of other causes. 

Idiosyncratic drug-induced liver injury is rare, even among patients who are exposed to potentially hepatotoxic medication, and few patients with drug-induced liver injury have progression to encephalopathy and acute liver failure. Factors such as an older age, increased elevations in blood aminotransferase and bilirubin levels, and coagulopathy are associated with an increased risk of death.