A decade of chronic hepatitis E treatment: Ribavirin effectiveness, safety, and the association of Torque Teno Virus load with treatment outcomes.

BACKGROUND: Hepatitis E virus (HEV) affects immunocompromised individuals. Unlike immunocompetent hosts, who rarely develop chronic infection, up to two-thirds of immunocompromised patients progress to chronicity. Ribavirin is the recommended antiviral therapy, yet predictors of sustained virological response (SVR) remain unclear. Torque Teno Virus (TTV), a marker of immunosuppression, has been proposed as a potential predictor of viral clearance. OBJECTIVES: We evaluated ribavirin treatment outcomes and adverse effects in immunocompromised patients with HEV infection, and assessed whether TTV load predicts SVR. STUDY DESIGN: A retrospective cohort study was conducted at the University Medical Center Groningen including solid organ transplant recipients (SOTR) and haematology patients treated with ribavirin for HEV infection between 2010 and 2022. Clinical data and stored serum samples were analysed to determine infection duration and TTV load at treatment initiation and after three months. TTV loads in treated patients were compared with TTV loads of transplant recipients who spontaneously cleared HEV. RESULTS: Fifty-two patients received ribavirin; 27 had confirmed chronic infection. SVR was achieved in 81% of chronic cases. Adverse events occurred in 56%, leading to dose reduction in 25% and discontinuation in 17%. Non-SVR was associated with ribavirin dose reduction, lower mean daily dose, higher baseline HEV RNA, and lower ALT. Baseline TTV load showed a nonsignificant trend toward higher levels in non-SVR patients. TTV loads did not differ between treated patients and spontaneous clearers. CONCLUSIONS: Ribavirin is effective for chronic HEV, but treatment-limiting toxicity is common. Adequate dosing appears critical for achieving SVR. TTV load did not reliably predict treatment outcome, underscoring the need for further research into immunological and virological predictors of response.