A BIPHASIC PATTERN OF ANTI-PRE-S RESPONSES IN ACUTE HEPATITIS-B VIRUS-INFECTION

The clinical relevance of the immune response to the translation products of the pre-S1 and pre-S2 regions of hepatitis B virus was examined by testing sequential serum samples from 17 patients with acute self-limited hepatitis B and from two patients in whom chronic liver disease developed. Anti-pre-S antibodies were determined by enzyme immunoassays based on the inhibition of binding of monoclonal antibodies to epitopes in the pre-S1 and pre-S2 sequence. In acute, self-limited infection, anti-pre-S antibodies appeared in a biphasic pattern. The early antibodies were detected at the time of clinical signs of acute disease when HBsAg and often HBeAg were present, but hepatitis B virus DNA was no longer detectable in serum. Anti-pre-S levels then fell, but subsequently reappeared as the late antibody during the recovery phase, after development of anti-HBe, but before anti-HBs. Anti-pre-S responses were detected in 15 of 17 patients who recovered (88.2%) and in both patients with acute hepatitis B virus infection evolving to chronic liver disease. Although the early antibodies to pre-S1 and pre-S2 proteins appeared at the time of decreasing levels of infectious virus in serum in cases of self-limited infection, these antibodies also were transiently or continuously present with high levels of serum hepatitis B virus DNA in patients in whom chronic hepatitis B infection developed. Thus the anti-pre-S response in acute hepatitis is not a prognostic marker for clinical resolution. Mechanisms other than a lack of humoral anti-pre-S responses must be responsible for the failure to eliminate virus in acute hepatitis B evolving into chronic infection.