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. (HEPATOLOGY 1990;12:1271–1277).