Risk factors associated with prolonged treatment courses of chronic hepatitis E

Abstract Background and aims Chronic hepatitis E virus (HEV) infection is a relevant complication in immunocompromised patients and remains therapeutically challenging due to variable response to ribavirin (RBV). We aimed to identify clinical and biochemical factors associated with prolonged or unsuccessful treatment courses. Methods In this retrospective single-center study, 41 patients with chronic HEV infection (HEV RNA detectable ≥ 12 weeks) treated between 2016 and 2024 were analyzed. Prolonged treatment (> 12 weeks), retreatment, or persistent viremia were defined as complicated treatment courses. Results The median patient age was 54 years. Ten patients (24.4%) were female. Transaminases were elevated at the time of diagnosis with a median ALT of 118 U/l and GGT of 127 U/l. Median elastography was 6.2 kPa. 4 patients died; 30/37 patients (81%) required ribavirin treatment. Out of those, HEV cure occurred after 12 weeks of ribavirin treatment in 16 patients (53.3%), whereas eleven patients (36.6%) needed longer treatment courses or retreatment. Three patients (10%) have an ongoing HEV infection. Male sex ( p = 0.03) and age > 50 years ( p = 0.04) were associated with complicated treatment courses. Both normal and high ALT levels (> 200 U/L) at baseline had poorer outcomes, and a BMI < 28 kg/m 2 was linked to prolonged viremia. Conclusion In this retrospective cohort, older age, male sex, and distinct ALT patterns were associated with complicated treatment courses. However, these exploratory findings require cautious interpretation given the limited sample size, heterogeneous patient population, and potential confounding. A subset of patients exhibits persistent infection despite therapy, underscoring the need for improved antiviral strategies and individualized management.