Serial sera were collected prospectively during the clinical course of 13 HBsAg carriers with chronic liver disease and analyzed for ALT levels, pre-S, and pre-S, antigens and corresponding antibodies and other serological hepatitis B virus markers. In five patients, anti-pre-S, and anti-pre-S, antibodies became detectable in multiple serum samples, whereas in eight patients anti-pre-S was never detected or only appeared transiently during the follow-up. The first pattern was associated with normalization of ALT levels and undetectable pre-S antigens and viral DNA by the polymerase chain reaction assay at final follow-up. HBsAg clearance occurred in two of the five patients. The second pattern was one of persistence of HBsAg and pre-S antigens, associated with the presence of serum HBV DNA detectable by spot hybridization or polymerase chain reaction regardless of clinical outcome. These findings demonstrate the occurrence of anti-pre-S antibodies in chronic hepatitis B virus-induced liver disease and associate anti-pre-S appearance with the clearance of hepatitis B v i m from serum. (HEPATOLOGY 1992;15:26-31.)
The envelope of HBV contains three related proteins, encoded by the S open reading frame of the viral genome, composed of three regions: pre-S,, pre-S, and S. The major protein, termed small HBs protein, is encoded by the S region, whereas the two minor envelope proteins, termed the middle protein and the large protein, are encoded by the pre-S, + S and pre-S, + pre-S, + S regions, respectively (1). The pre-S domains of the large protein and the middle protein represent potential viral attachment sites to hepatocytes (2) and elicit antibodies capable of neutralizing HBV in uitro (3) and in experimental models (4).
The role of the anti-pre-S immune responses in viral clearance and in the pathogenesis of disease is not fully understood. In acute uncomplicated HBV infection, the