Significance of anti‐HBx antibodies in hepatitis B virus infection

Serological responses to hepatitis B virus–X determinants have been noted in human sera, but conflicting findings concerning the correlation of anti‐HBx antibodies with different stages of hepatitis B virus infection or pathological sequelae have been reported. Using an adenovirus‐based eukaryotic vector, the 17 kD X protein was efficiently expressed in 293 cells. Cellular extracts containing the eukaryotic X protein have been used to screen for anti‐HBx antibodies by immunoblot analysis in a large panel of sera from patients affected by hepatitis B virus chronic hepatitis, hepatocellular carcinoma and acute viral hepatitis. Sera from 32 of 171 (19%) chronic hepatitis B virus patients were positive for anti‐HBx antibodies. Only one of thirty‐two (3%) HBsAg‐negative, anti‐HBs/anti‐HBc—positive chronic hepatitis serum was anti‐HBx positive. Very few sera from primary hepatocellular carcinoma patients showed positivity for anti‐HBx (8 of 149 or 5%). Anti‐HBx were also detected in 8 of 48 (17%) acute viral hepatitis patients. In the four cases that were followed up weekly, anti‐HBx anti‐bodies appeared 3 to 4 wk after the onset of the clinical signs. To compare the X protein expressed in eukaryotic and prokaryotic cells as a substrate for anti‐HBx antibody detection, 171 sera were screened with HBx fusion proteins expressed in Escherichia coli . The prokaryotic cell extract test seems to be more sensitive. During the chronic phase of hepatitis B virus infection, the presence of anti‐HBx antibodies detected with the eukaryotic cell extract correlates with the presence of well‐established markers of ongoing viral replication: serum hepatitis B virus‐DNA (p < 0.001) and intrahepatic HBcAg expression (p < 0.001). (H EPATOLOGY 1991;13:143—149).