Role of Immunomodulators in Functional Cure Strategies for HBV
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HEPATITIS B (JK LIM, SECTION EDITOR)
Role of Immunomodulators in Functional Cure Strategies for HBV Benedikt Binder 1,2 & Maike Hofmann 1,3 & Robert Thimme 1,3
# The Author(s) 2020
Abstract Purpose of Review Chronic Hepatitis B Virus (HBV) Infection is a major global health burden. Currently, a curative therapy does not exist; thus, there is an urgent need for new therapeutical options. Viral elimination in the natural course of infection results from a robust and multispecific T and B cell response that, however, is dysfunctional in chronically infected patients. Therefore, immunomodulatory therapies that strengthen the immune responses are an obvious approach trying to control HBV infection. In this review, we summarize the rationale and current options of immunological cure of chronic HBV infection. Recent Findings Recently, among others, drugs that stimulate the innate immune system or overcome CD8+ T cell exhaustion by checkpoint blockade, and transfer of HBV-specific engineered CD8+ T cells emerged as promising approaches. Summary HBV-specific immunity is responsible for viral control, but also for immunopathogenesis. Thus, the development of immunomodulatory therapies is a difficult process on a thin line between viral control and excessive immunopathology. Some promising agents are under investigation. Nevertheless, further research is indispensable in order to optimally orchestrate immunostimulation. Keywords Hepatitis B . Immunology . Immunotherapy . CD8+ T cells . Exhaustion . Checkpoint blockade
Introduction Despite the existence of an efficient vaccine, chronic Hepatitis B Virus (HBV) infection is a major global health burden with an approximate number of 257 million infected individuals and 887,000 deaths per year worldwide [1]. The risks of chronic HBV infection include progressive liver disease possibly leading to the development of liver fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC). The fact that HBV is a non-cytopathic virus implies that the liver inflammation as indicated by elevated serum liver enzymes in patients is caused by virus-mediated immunopathogenesis.
This article is part of the Topical Collection on Hepatitis B * Robert Thimme [email protected] 1
Department of Medicine II, University Hospital Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany
2
IMM-PACT Clinician Scientist Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany
3
Faculty of Medicine, University of Freiburg, Freiburg, Germany
Current therapeutic options include treatment with pegylated interferon alpha (pegIFNα) and nucleoside-/ nucleotide-analogues (NUCs). In the majority of cases, these drugs are capable of limiting hepatic inflammation and viral replication. Nevertheless, viral elimination is barely achieved and HCC development is still not completely abrogated [2, 3], implicating long-time treatment and consequent frequent medical attendance. There are different definitions of cure in the context of HBV infection. Partial cure is defined as n
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