Changing etiologies and outcomes of acute liver failure: A perspective from Japan.

Acute liver failure in Japan usually consists of fulminant hepatitis (FH) due to viral infection, autoimmune hepatitis and drug-allergy-induced liver injury. The annual incidence of FH was estimated at 429 cases in 2004. FH is classified into acute or subacute type, and the prognosis of the latter is poor. Hepatitis B virus (HBV) is the most frequently identifiable agent that causes FH in Japan. Transient HBV infection is more prevalent in the acute than subacute type, whereas the frequency of HBV carriers is greater in the subacute type. FH due to HBV reactivation from resolved hepatitis B has been increasingly observed in patients with malignant lymphoma treated with rituximab and corticosteroid combination therapy. The prognosis is poor in HBV carriers with acute exacerbation, especially in patients with HBV reactivation from resolved hepatitis B. Despite careful investigation, the etiology is still unknown in 16% and 39% of the acute and subacute type of FH, respectively. Autoimmune hepatitis and drug-allergy-induced liver injury are found in 7% and 10%, respectively, and are more frequently observed in the subacute type of FH. Living donor liver transplantation is now the standard care for individuals with poor prognosis. Artificial liver support with plasmapheresis and hemodiafiltration plays a central role while waiting for a donor liver or for the native liver to regenerate. Further research is necessary to identify the causes of unknown origin. In addition, to improve the prognosis of FH, it is necessary to establish treatment modalities that are effective for liver regeneration.