Oral Zinc Supplementation in Chronically HEV-Infected Patients Not Responding to Ribavirin Monotherapy

Abstract

Background: Chronic hepatitis E virus (HEV) infection may progress to end-stage liver disease in immunosuppressed individuals. Ribavirin therapy is efficient in most chronic HEV patients, but 10% remain without a sustained virological response (SVR). Objectives: We aimed to study whether zinc supplementation could represent a therapeutic approach in these patients. Methods: Antiviral properties of zinc salts were studied in vitro (subgenomic-replicon system), in vivo (rabbit model), and retrospectively in patients with chronic hepatitis E who did not achieve SVR under ribavirin monotherapy. Results: Zinc inhibited HEV genotype-3 replication in vitro. In a model of acute HEV infection in immunocompetent rabbits, zinc + ribavirin did not improve viral clearance compared to ribavirin monotherapy. In chronically HEV-infected patients not responding to ribavirin (n = 12), viral clearance was observed in 4/12 (33%) patients receiving additional zinc supplementation. Conclusions: Oral zinc, an inexpensive, harmless dietary supplement, could potentially represent a rescue treatment option for a few patients with chronic hepatitis E without SVR under ribavirin monotherapy. Further studies are needed to elucidate the role of zinc in HEV further.