Incidence, predictors and prognosis of genotype 4 hepatitis E related liver failure: A tertiary nested case‐control study

Abstract Background/Aims Hepatitis E virus (HEV) infection has been recognized an important insult of acute or acute‐on‐chronic liver failure (A(C)LF). This study aimed to identify the incidence, predictors and outcomes of A(C)LF in patients with hepatitis E. Methods All patients diagnosed of hepatitis E between 2012 and 2018 in the tertiary hospital were retrospectively and consecutively analysed. Patients with hepatitis E who developed A(C)LF were enrolled as cases (HEV‐LF) and controls were randomly selected from those who did not develop liver failure with 1:3 ratio in the same cohort. Results Eight hundred and nine patients were diagnosed with hepatitis E, among which 80 were identified with HEV‐related liver failure (HEV‐LF) with HEV as the solely acute aetiology of A(C)LF. Sequencing of HEV genome showed genotype (GT) 4 strains in all available serum samples. Hepatitis E patients with cirrhosis underwent higher risk to develop liver failure, compared to non‐cirrhotic patients. Hydrothorax, respiratory infections, lower γ‐glutamyl transferase, higher lactate dehydrogenase and alpha‐foetoprotein were found to be independent predictors of A(C)LF in patients with hepatitis E. The 28‐day and 90‐day mortality for HEV‐LF was 12.86% and 30.36% respectively. Renal injury and lower triglyceride were independent factors associated with 28‐day mortality. Lower alanine aminotransferase and higher International normalized ratio were independent predictors of 90‐day mortality. Conclusions Patients with GT4 hepatitis E are at high risk to develop A(C)LF. Different CLD status impacted the incidence of HEV‐LF distinctively. The identified variables shall help to identify HEV patients with high risk for developing liver failure and the risk for death.