Therapeutic window for ribavirin therapy in transplant recipients with chronic hepatitis E virus infection

M.B. Mulder, R.A. de Man, N. Kamar, G. Durmaz, J. de Bruijne, T. Vanwolleghem, A.A. van der Eijk, T. van Gelder, D.A. Hesselink, B.C.M. de Winter

Thursday 5 march 2020

13:50 - 14:00h at Leo Franssen zaal

Parallel session: Parallel sessie XIV– Klinische abstracts

Background: The optimal dose, target concentration and duration of ribavirin (RBV) therapy in solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients with chronic hepatitis E virus (HEV) infection are unknown. The aim of this study was to investigate the association between RBV plasma concentrations and virologic response and anemia. Next, to define the therapeutic window for ribavirin in SOT and HSCT recipients with a chronic HEV infection.

Methods: In this retrospective, multicenter, cohort study, data of adult SOT and HSCT recipients with chronic HEV infection, who had been treated with RBV monotherapy between 2008 and 2018 were included. Data were collected in four European university hospitals. Receiver operating characteristic curve analyses were performed and the half-maximal effective concentration was calculated to determine a representative therapeutic window. Factors associated with a sustained virologic response (SVR) were investigated using multiple binary logistic regression analysis. A SVR was defined as an undetectable level of HEV RNA in serum at least 6 months after completion of ribavirin therapy. A clinically relevant response to ribavirin was defined as a decrease of the HEV RNA load after the initiation of ribavirin therapy with at least a factor 2. No response was defined as a rise in the HEV load.

Results: A total of 96 patients with 300 RBV plasma determinations (ribavirin concentration range 0.10–7.40 mg/L) were included. RBV monotherapy for a median of three months resulted in a SVR in 62.5% of the patients and 88.5% of the patients developed anemia. RBV plasma concentrations at steady-state were significantly higher in the response group compared to the non-response group: median 1.96 (IQR 1.81–2.70) versus 0.49 (IQR 0.45–0.73) mg/L, p=0.0004. RBV caused dose-dependent hemoglobin reduction with higher RBV plasma concentrations resulting in more hemoglobin reduction.

Conclusions: RBV monotherapy resulted in a SVR in 62.5% of the patients. RBV plasma concentrations at steady-state were significantly higher in the group with a virologic decline. The therapeutic window for RBV for treating a chronic HEV infection in SOT and HSCT recipients ranges between 1.8 and 3.0 mg/L.