Roles of inflammatory factors in the pathogenesis of hepatitis B virus-related acute-on-chronic liver failure and CAR-T therapy

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) pathogenesis remains unclear. Cytokine release syndrome (CRS) is a serious concomitant disease caused by pathogen infection and immunotherapies, such as HBV infection and chimeric antigen receptor T (CAR-T) therapy respectively while the role of inflammatory factors (IFs) in such patients still remains to be elucidated. This study aims to explore HBV-ACLF pathogenesis according to analyze IFs changes in patients with HBV-ACLF, prophase of HBV-ACLF(pro-HBV-ACLF) and CAR-T therapy, and the relationship between IFs and liver function indexes (LFIs) in patients receiving CAR-T therapy. The clinical records of 68 patients with HBV-ACLF, 30 patients with pro-HBV-ACLF, and 372 patients with hematologic tumors but without abnormal liver function who received CAR-T therapy at the First Affiliated Hospital of Soochow University were retrospectively examined in this investigation. Serum interleukin-10 (IL-10) levels was significantly increased from healthy controls to pro-HBV-ACLF and to HBV-ACLF. IL-10 was decreased in patients who experienced improvement compared to those whose condition deteriorated. Consistently, alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) and international normalized ratio (INR) also increased with the development of HBV-ACLF. However, IL-6 did not significantly change from pro-HBV-ACLF to HBV-ACLF and to HBV-ACLF without infection, while IL-6 was even lower in patients with HBV-ACLF without secondary infection than in patients with pro-HBV-ACLF. In addition, Serum levels of IL-2, IL-10, tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ), especially IL-6, increased significantly after CAR-T treatment in tumor patients, while TBIL and ALT levels did not markedly increase. These results elucidate the role of inflammatory factors in the pathogenesis of HBV-ACLF and the side effects of CRS induced by CAR-T therapy.