Incidence, Predictors and Prognosis of Liver Failure in Patients with Hepatitis E as an Acute Insult

Background: Genotype (GT) 3 and GT4 hepatitis E virus (HEV) infection has been recently recognized as an important insult of acute or acute-on-chronic liver failure (A(C)LF). This study aimed to identify incidence, predictors and outcomes of GT4 HEV related liver failure (HEV-LF).   Methods: All patients with symptoms of suspected acute viral hepatitis were screened for HEV infection in a tertiary hospital. Patients with hepatitis E who developed or not developed A(C)LF were recruited as cases and controls, respectively.   Findings: 62 (8.41%) of 737 hepatitis E patients developed liver failure with HEV infection as an acute event during the study period. Sequencing of HEV genome confirmed GT4 HEV strains. At multivariate analysis, ascites, spontaneous peritonitis, intestines injury, lactate dehydrogenase, alpha fetoprotein and carbohydrate antigen 125 were found to be independent predictors of A(C)LF during hospitalization. Of the 62 HEV-LF patients, 40 (64.52%) became recovered/improved, 20 (32.25%) were failed to treatment and 2 (3.23%) died. Presenting hepatic encephalopathy, higher glucose and international normalized ratio were independent predictors of poor prognosis of HEV-LF. Cirrhosis is the predominant chronic liver disease (CLD) that associated with development and poor prognosis of A(C)LF, compared to alcoholic liver disease and chronic hepatitis B.   Interpretation: Patients with GT4 hepatitis E are at high risk to develop liver failure, especially in patients with CLD. Different types of CLDs impacted the incidence and prognosis of HEV-LF distinctively. The identified variables shall help to identify HEV patients with high risk of developing liver failure and the risk population with poor outcomes. Funding Statement: This work was supported by National Natural Science Foundation of China [31770186 and 81802020 to Y.W.]. Declaration of Interests: All authors declare no conflict of interests. Ethics Approval Statement: Ethical approval was obtained from the Institutional Ethics Committee of Beijing 302 hospital.