Background: Despite acute hepatitis E virus (HEV) infection is a self-limiting acute infection, it could be a cause of acute on top of chronic liver failure (ACLF) in patients with chronic liver disease. Thus, identification role of HEV superinfection in deterioration of liver cirrhosis with early treatment could save life of those patients. Aim: Todetermine the percentage and the role of HEV infection in order to detect outcomes of patients with ACLF, to find effect of HEV infection on liver, kidney functions and coagulation profile, and to find specific clinical or laboratory characteristics of these patients if present. Subjects and methods: This cross-sectional study was conducted at Tropical Medicine Department. and Clinical Pathology Department, Zagazig University Hospitals on patients with liver cirrhosis; either compensated, decompensated (who admitted for ascites for control, follow up upper GIT endoscope, spontaneous bacterial peritonitis) or in those who have chronic liver disease and experience acute hepatic decompensation, which leads to acute liver failure (jaundice, prolonged INR), as well as one or more extrahepatic organ failures. All patients had standard laboratory evaluations, including the detection of HEV IgM by ELISA technique. Results: The incidence of HEV was 18% in ACLF cases and ACLF cases with positive HEV showing higher MELD score than ACLF cases with negative HEV. Conclusion: ACLF cases with positive HEV have higher MELD score than ACLF cases with negative HEV (statistically significant) but regarding Child score, there was statistically non-significant difference.