Pathways to better treatments for autoimmune liver diseases unveiled

A review published by researchers at the University of Birmingham revealed new insights into the complex dynamics of immune cells in the liver, paving the way for the development of innovative and targeted treatments for autoimmune liver diseases.

The review, published in the Journal of Hepatology, explores how lymphocytes — an essential subset of immune cells — navigate the complex pathways leading to the liver. By decoding the signals that steer these cells and examining their interactions with other liver cells, the review provides a clearer picture of how disruptions in these processes contribute to autoimmune liver diseases like autoimmune hepatitis and primary biliary cholangitis.

A key type of liver cell interaction is where immune cells enter liver cells, generating so-called “cell-in-cell” structures. These are particularly common in autoimmune liver disease patients which warrant further studies to explore treatment avenues.

One of the processes that generate these structures, called AVentosis, has only recently been discovered by author Dr Scott Davies and his team, and research is currently underway to determine if blocking the interactions that lead to the formation of cell-in-cell structures might prevent immune cells from attacking liver cells and lead to liver disease progression.

The review also compares autoimmune liver diseases, such as autoimmune hepatitis, with liver damage caused by cancer treatments called checkpoint inhibitors. Checkpoint inhibitor-induced liver injury (CHILI) involves different immune responses, highlighting the need for accurate diagnosis and tailored treatment strategies. This distinction is critical as checkpoint inhibitors become more widely used in cancer therapy.

The review highlights several promising avenues for treatment of autoimmune liver diseases, which include immune-based therapies, cytokine supplementation, and Bispecific T cell engagers (BiTEs) and their next-generation counterparts, checkpoint inhibitor bispecific T cell engagers (CiTEs), which precisely target immune pathways.

The authors explain that leveraging cutting-edge approaches, such as Individualised Pharmacotherapy based on Omics Pathway (IPOP), could pave the way for personalised treatments tailored to a patient's unique immune profile, thereby improving patient outcomes.

Ye Oo, Professor of Autoimmune Liver Diseases and Translational Hepatology at the University of Birmingham’s Department of Immunology and Immunotherapy and researcher within the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, added: “These advancements in discovery science, diagnostics, and therapies mark a transformative era in hepatology and immunotherapy, offering new hope for patients to effectively manage these challenging conditions.”