Hepatitis B virus: Latest topics

People living with hepatitis B virus (HBV) chronic infection are exposed to high rates of liver complications including end-stage liver disease and hepato-cellular carcinoma. Extrahepatic manifestations of HBV infection have long been under-estimated. Several of these extrahepatic syndromes have been well described, including systemic vasculitides, glomerulonephritis, and cutaneous manifestations. Other manifestations have been more recently described such as hematological malignancies and neurological diseases. These extra-hepatic manifestations are associated with significant morbidity and mortality. Although not completely understood, underlying mechanisms include HBV-induced local and systemic inflammation. Suppression of HBV replication usually improves extra-hepatic manifestations.
The development of effective treatments for hepatitis C virus has led to hope for a cure for HBV. Current treatments for HBV infection include pegylated interferon-alfa, which is associated with modest efficacy and poor tolerability, or nucleoside analogues, which require lifelong administration and rarely achieve hepatitis B surface antigen (HBsAg) loss. Understanding the HBV lifecycle is essential to develop new approaches, since each step is a potential target for drug development. New direct-acting antivirals for HBV in development include entry inhibitors, capsid assembly modulators, and drugs targeting cccDNA or HBV RNA, and HBsAg secretion inhibitors. In this lecture, will discuss how HBV induces inflammation and the extra-hepatic manifestations of HBV infection to guide clinical management. We will also discuss potential targets and direct-acting antiviral approaches in development.