EXPRESSION OF THE TERMINAL PROTEIN OF HEPATITIS-B VIRUS IS ASSOCIATEDWITH FAILURE TO RESPOND TO INTERFERON THERAPY

The terminal protein domain of the hepatitis B viral polymerase can in hibit the cellular response to interferon. To clarify the clinical rel evance of this inhibitory effect, we examined the expression of termin al protein in liver biopsy specimens from patients with chronic hepati tis B infection. We found that expression of terminal protein is assoc iated with a failure of hepatocytes to respond to interferon, as asses sed by expression of the interferon-inducible protein beta2-microglobu lin. Patients whose liver specimens contained large numbers of cells e xpressing terminal protein tended not to respond to treatment. During interferon therapy the percentage of cells expressing terminal protein remained constant, but treatment significantly reduced the number of cells that expressed the hepatitis B nucleocapsid protein. Hence expre ssion of terminal protein in a cell may prevent elimination of the vir us by interferon therapy.