Immune Therapeutic Strategies in Chronic Hepatitis B Virus Infection: Virus or Inflammation Control?

More than 240 million people worldwide are infected with hepatitis B virus (HBV) and are at risk of developing liver cirrhosis and hepatocellular carcinoma (HCC). Reducing this pool of infected people is a necessity since despite an effective prophylactic vaccine, about 2% of the vaccinated individuals in high endemic areas still develop chronic HBV infection (CHB). A battery of antiviral drugs based on nucleoside or nucleotide analogues that target the HBV reverse transcriptase are available. They efficiently suppress HBV replication and reduce liver inflammation linked with cirrhosis but rarely achieve virus eradication. HBV is present in hepatocytes in a mini-chromosomal form (called cccDNA) that is untouched by reverse transcriptase inhibitors. As a consequence, response to the treatment is hardly durable and a majority of patients experience HBV reactivation when antiviral therapy is withdrawn [1]. Failure to achieve sustained control of HBV infection is linked with an inability to elicit an effective immune response that resembles one present in adult patients that resolve acute infection. However, since HBV is a non-cytopathic virus, immunological processes are also responsible for the chronic inflammatory events that cause cirrhosis and HCC [1]. Immunotherapeutic approaches primarily designed to control viral replication through the boosting of antiviral immunity or that aim to inhibit the liver inflammatory processes linked with cirrhosis and HCC development will be discussed.