Chronic hepatitis delta virus infection leads to functional impairment and severe loss of MAIT cells.

•Mucosa-associated invariant T (MAIT) cells are severely depleted in peripheral blood of HDV-infected patients.•Residual MAIT cells display a distinct CD38hiPD-1hiCD28loCD127lo compound phenotype.•Residual MAIT cells are functionally impaired in response to bacteria.•Patients with HDV exhibit signs of microbial translocation and increased IL-12 and IL-18.•IL-12 and IL-18 induce an activated MAIT cell phenotype and promote apoptosis.