BACKGROUND & AIMS: The role of hepatocytes in producing chemokines and triggering liver inflammation and damage in chronic hepatitis D (CHD) is not fully understood. Herein, we investigated the contribution of primary human hepatocytes (PHHs) infected with HDV in triggering inflammation by producing the chemokines CXCL9-11. METHODS: We performed quantitative PCR, RNA RESULTS: In patient and chimeric mouse livers, higher expression levels of CXCL9-11 were found in an HBV/HDV-coinfected CONCLUSIONS: HDV infection upregulated the intrahepatic expression of the CXCL9-11/CXCR3 receptor/ligand axis. Higher amounts of HBV/HDV-unspecific CD4 T cells expressing CXCR3 may contribute to the aggravated liver inflammation frequently observed in patients with CHD. IMPACT AND IMPLICATIONS: Chronic hepatitis D (CHD) causes the most severe form of viral hepatitis, and treatment options are still limited
therefore, a more precise understanding of CHD immunopathology is needed. In this study, we demonstrated that HDV infection triggers CXCL9-11 expression in hepatocytes and liver infiltration of CXCR3-expressing CD4 T cells in preclinical models as well as patient biopsies. Because recruitment of Th1-polarised CD4 T cells to the liver has been also described for other severe liver diseases, such as autoimmune hepatitis, it may represent an important mechanism of aggravating liver diseases. The data of this study set hereby the basis for future studies analysing phenotype and function of intrahepatic T cells in CHD.