Azathioprine Inhibits Hepatitis A Virus Replication In Vitro

Hepatitis A virus (HAV) infection can occasionally cause acute severe hepatitis. Patients with this disease sometimes need to undergo liver transplantation with immunosuppressants. Although rare, breakthrough HAV infections, despite vaccination, appear to be more common among immunocompromised populations. The effect of immunosuppressants on HAV replication is unclear. In this study, we examined the effects of immunosuppressants on HAV HA11-1299 genotype IIIA replication in human hepatocytes, finding that azathioprine inhibited HAV replication with a half-maximal inhibitory concentration of 0.967 μmol/L. We further examined the effect of azathioprine on the replication of HAV HM175 18f genotype IB using replication-competent or replication-incompetent subgenomic replicon in HuhT7 cells. Azathioprine had significant inhibitory effects on the HAV replication-competent subgenomic replicon compared to the replication-incompetent subgenomic replicon. The effect of azathioprine on the activity of the HAV HM175 18f genotype IB-internal ribosomal entry site (IRES) was investigated in COS7-HAV-IRES cells using a reporter assay. Azathioprine at 1 μmol/L had a significant inhibitory effect on HAV IRES activity but at 0.5 μmol/L had no inhibitory effect. Azathioprine appears to inhibit HAV replication as well as HAV translation. In conclusion, we found that azathioprine inhibits HAV replication in human hepatocytes, meaning that it may be useful for patients with a HAV infection who need to use immunosuppressants.