Engineered IFN-{alpha} and anti-PDL1 containing compounds to target the liver and restore antiviral protection for HBV cure

Chronic HBV infection, with hepatic inflammation and viral genome persistence in the hepatocytes either in the form of cccDNA or partially integrated into the host nucleus, is one of the major causes of liver cirrhosis and hepatocellular carcinoma.1 Available therapies for chronic hepatitis B (CHB) include long-term administration of nucleos(t)ide analogues or a finite treatment with polyethylene-glycol (PEG)–interferon alpha (IFN-α) that rarely allow reaching a functional cure, defined as loss of Hepatitis B surface antigen (HBsAg) and undetectable HBV DNA in the serum.1 Thus, a major effort is currently devoted to studies aimed at finding new effective therapies. Different factors contribute to viral persistence. HBV can elude the host immune response, being poorly detected by the innate system and inducing variable degrees of dysfunction of the adaptive immune response up to T-cell and B-cell exhaustion in chronic infection. Moreover, the liver represents a peculiar tolerogenic...
Source: Gut - Category: Gastroenterology Authors: Tags: Gut Commentary Source Type: research