Abstract
Chronic hepatitis delta (CHD) represents the most severe form of viral hepatitis due to rapid disease progression towards liver cancer, leading to high morbidity and mortality. Hepatitis delta virus (HDV) can only infect individuals who are infected with hepatitis B. So far, there is no cure or vaccine for HDV. Existing treatment options, including pegylated interferon-α and hepatocyte entry inhibitors, offer limited efficacy. Emerging therapeutic strategies are focused on targeting various steps of the HDV life cycle or enhancing the host immune response to promote viral elimination. A defective antiviral immune response is increasingly recognized as a culprit for HDV persistence; however, the precise immunological mechanism associated with disease progression and pathogenesis has not been well defined. This review provides an update on the current understanding of host immune response in CHD, highlighting its role in both disease pathogenesis and viral clearance. A deeper understanding of these immune correlates may lead the way to novel treatment strategies, including immunotherapies targeting host immune response that can be used in combination with other antiviral therapies to achieve more effective and durable treatment outcomes.