THE HEPATITIS-B VIRUS AND THE HOST RESPONSE

The clearance of hepatitis B virus infected cells from the liver is probably dependent on an interplay between the interferon system and the cellular limb of the host immune response. Although the importance of the nucleocapsid proteins as targets for sensitized cytotoxic T cells is established in chronic hepatitis B infection, further studies are needed during the early phase of acute infection. The relative importance of pre-S sequences as inducers and targets of the virus neutralizing humoral immune response is becoming established but their precise place will await the development of in vitro models of hepadna virus infection and precise definition of the mechanism of viral uptake. In adult life, deficient production of alpha-interferon and suppression of the ability of the host to respond to interferon are probably important factors underlying the development of chronic infection. In the neonate, however, specific suppression of the cell-mediated immune response may be involved. The presence of a mutation in the pre-core region of some virus isolates has recently been described. Hepatocytes infected with this virus cannot produce hepatitis B e antigen and the course of the liver disease is fairly rapid. Whether this mutant causes liver damage in the same way as the wild virus or is directly cytopathic needs further study. In adult-acquired chronic hepatitis B virus infection, alpha-interferon produces hepatitis B e antigen clearance in 26-88% of cases and is followed by resolution of the hepatic inflammation. Results in neonatally acquired infection are less impressive and prednisolone priming followed by interferon may be needed. The value of interferon in the treatment of patients infected with the pre-core mutant remains to be established.