Janus kinase inhibitors modulate hepatitis E virus infection

Hepatitis E usually is a self-limiting disease, but especially immunocompromised individuals are at risk to develop a chronic and severe course of infection. Janus kinase inhibitors (JAK-I) are a novel drug class for the treatment of autoimmune inflammatory rheumatic disease (AIRD). As JAKs play a key role in innate immunity, viral infections and reactivations are frequently reported during JAK-I treatment in AIRD patient. With the aim to assess the risk of HEV infection during JAK-I therapy, we monitored the presence of HEV RNA, HEV-Antigen and anti-HEV IgG/IgM in RA patients receiving JAK-Is. Furthermore, we identified a AIRD patient under JAK-I therapy with hepatitis E and increased liver enzymes. Transcriptomic analysis of primary human hepatocytes (PHHs) revealed an induction of antiviral programs during HEV infection. This induction was perturbed in the presence of a JAK-I, concomitant with strong elevation of HEV RNA levels. In line, infection experiments displayed an up to 50-fold increase of progeny virus production during JAK-I treatment indicating that JAK signaling is critical to control HEV infection. As our data raise potential concern, screening for HEV seroprevalence and HEV RNA should be considered prior starting JAK-I treatment and in case of elevated liver enzymes during JAK-I therapy.

Publication History

Article published online:
18 January 2023