Background and aims: Hepatitis E virus (HEV) infection is very frequent in Europe with more than 2 million annual infections. Patients with liver cirrhosis may face an increased risk of suffering from acute-on-chronic liver failure (ACLF) due to HEV infection. We explored the consequences and prevalence of HEV infection in individuals with liver cirrhosis.
Methods: We retrospectively analysed the clinical outcome of all consecutive patients who were hospitalized at our center due to acute HEV infection and analysed their outcome between 2014 and 2024. Next, we tested 249 sera from 184 cirrhotic patients during individual episodes of acute hepatic decompensation for anti-HEV IgM and HEV-RNA to analyse the relevance of acute HEV infection as a triggering event. Finally, we established a single center cohort of patients with advanced liver cirrhosis, and assessed the anti-HEV IgG seroprevalence (n = 332).
Results: Over the past decade, 32 patients with liver cirrhosis who were hospitalized due to acute HEV infection were identified. Among these patients, 16 (50%) developed ACLF, resulting in five fatalities (31.3%) and three individuals (18.8%) requiring liver transplantation for survival. Of 249 sera obtained during acute hepatic decompensation, 11 (4.4%) were either HEV-RNA positive (n = 2) and/or anti-HEV IgM positive (n = 10), linking HEV infection to these acute decompensations. Screening of patients with liver cirrhosis for anti-HEV IgG showed that 67.2% of patients (223/332) were anti-HEV negative and thus at potential risk for future HEV infection.
Conclusions: Patients with advanced liver cirrhosis are at risk of acute HEV infection, which is a relevant cause of hepatic decompensation and ACLF with high mortality in these patients.
Trial registration: DRKS00010664; NCT04801290.
Keywords: ACLF; HEV; liver cirrhosis; seroprevalence.
Hepatitis E virus (HEV) infection is the most common cause of acute viral hepatitis worldwide and may have particularly serious consequences for patients with advanced liver cirrhosis. In this study, we investigated the impact and frequency of HEV infection in patients with cirrhosis in a large tertiary centre in northern Germany. Among 32 patients hospitalized with acute HEV infection, half developed acute‐on‐chronic liver failure (ACLF), a severe and life‐threatening complication. Five patients died and three required liver transplantation. We also found evidence of recent HEV infection in approximately 4% of episodes of acute hepatic decompensation, indicating that HEV can act as a trigger for clinical deterioration in patients with cirrhosis. In addition, about two‐thirds of patients with advanced cirrhosis had no evidence of previous HEV exposure and therefore remained susceptible to infection. These findings suggest that HEV is an underrecognized cause of hepatic decompensation and ACLF in patients with advanced liver disease. Greater awareness and routine testing may improve detection, whereas effective preventive and therapeutic strategies for this vulnerable patient population are lacking.
© 2026 The Author(s). Liver International published by John Wiley & Sons Ltd.