The liver is the largest solid organ in the body and has unique immunological properties, including induction of immune tolerance, strong innate immunity, poor adaptive immune response versus over-reactive autoimmunity. The liver continuously removes a continuous flux of a variety of pathogens, MAMPs and DAMPs from portal circulation ensuring organ protection while maintaining immunotolerance. Dysregulation of tightly controlled immunological tolerance and immunity network leads to liver diseases, including autoimmunity, infectious hepatitis, and tumor development. A greater understanding of the complex orchestration of the hepatic adaptive immune regulators during homeostasis and immune competence is needed to identify targets for clinical intervention.

Autoimmune liver disease immunopathology has been dissected widely, however, etiology and new therapy remain elusive. Recent advances in technology may help to guide us for a personalized medicine approach targeting immune pathways. New advances in immunotherapy for autoimmune liver diseases and the role of the microbiome will also play a major aspect in future treatments.

In acute HBV infection, virus-specific T cells might be functionally defective, and this exhaustion state is a key determinant of HBV persistence. The reconstitution of an efficient anti-HBV T cell response constitutes a potential strategy to treat chronic HBV patients. Promising immune-modulatory approach to treat the disease include checkpoint inhibitor blockade, specific T cell vaccines, autologous T cell engineering and chimeric antigen receptor (CAR) T cells. In chronic HCV infection, a vaccine would prevent transmission, and significantly reduce the global burden of HCV-associated disease. However, there are many hurdles to its development including virus diversity, limited models for testing vaccines, and our incomplete understanding of protective immune responses.
As such, further studies discussing the development of new vaccines for HCV infections are of great importance in the field.

Other rising chronic liver conditions such as alcoholic liver disease (ASH) and nonalcoholic fatty liver disease (NAFLD) see the role of innate and adaptive immunity as an additional factor promoting liver inflammation and fibrosis. They are both characterized by B cell and T cell infiltration of the liver as well as by the presence of circulating antibodies. Lymphocyte responses contribute to sustained hepatic macrophage activation and natural killer T cell recruitment. Targeting lymphocyte recruitment and/or activation ameliorates experimental steatohepatitis and NASH-associated liver fibrosis as well as experimental ASH.

In contrast to most other malignancies, hepatocellular carcinoma (HCC) arises almost exclusively in the setting of chronic inflammation of the liver and is resistant to chemotherapy. Immunotherapies have raised hope for the successful treatment of advanced HCC. However, the highly immunotolerant environment and tightly controlled protective mechanisms in the liver make the development of effective immunotherapies for HCC challenging. Finally, we aim at shedding new light on delivering technological innovations based on deep learning and digital pathology for the discovery of novel immune regulatory and suppressive pathways, directly enabling the identification of targetable immune regulatory pathways.

This Research Topic aims to provide state-of-the-art updates reviews on Liver Immunology with a focus on hepatic viral infections, metabolic diseases, hepatocellular carcinoma, and autoimmune disorders. Emphasis will be given on recent developments in the field and the impact of novel technologies. We welcome authors to submit Reviews focusing on:

• Autoimmune Liver Diseases
• Viral hepatitis and vaccines
• Role of the immune system in non-alcoholic fatty liver disease (NAFLD)
• Potential of immunotherapy for hepatocellular carcinoma (HCC)
• Novel therapeutic approaches to chronic liver diseases (stem cells transplantation, fecal microbiota transplantation)

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Frontiers in Immunology

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