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The data available on subacute hepatic failure due to hepatitis E virus is scarce. The aim of this study is to analyze the clinical spectrum and outcome of this condition.This is a retrospective hospital-based study of patients with acute hepatitis E and subacute hepatic failure from January 2001 to June 2006.We encountered 12 patients with this condition during the study period. There were four females and eight males (age 39 ± 16). Jaundice and ascites were present in all. The model for end stage liver disease (MELD) score was 25 ± 8. All of them had normal-sized liver on ultrasonogram. Transjugular liver biopsies were done in nine patients and revealed extensive bridging, submassive necrosis and cholestasis. Complications included spontaneous bacterial peritonitis (four) and urinary tract infections (two), renal failure (three) and encephalopathy (three). The in-hospital mortality was 25% (3/12). The remaining nine patients left the hospital alive with normalization of liver functions in eight of them over the next few months.Subacute hepatic failure caused by hepatitis E is a distinct entity with a better prognosis compared with the previously published series of subacute hepatic failure. Liver biopsy is useful to differentiate from hepatitis E virus superinfection on underlying chronic disease. Poor prognostic factors were female sex, younger age, encephalopathy and persistent renal failure. These patients should be considered for liver transplantation.