The finding that the recently described hepatitis B (HB)-associated delta antigen (8 Ag) is preserved in pronase-treated, formalin-fixed paraffin sections allowed a combined prospective and retrospective immunohistological study of its occurrence in 571 liver biopsies.
Among 116 frozen biopsies (69 HBAg seropositive, 47 HBAg seronegative) and 455 paraffinembedded biopsies (296 HBAg seropositive, 159 HBAg-negative), 6 Ag was found in 10 HBAg seropositive patients. With the exception of 1 patient with chronic persistent HB, all had chronicactive HB and none had acute HB; 5 patients were i.v. drug abusers. In follow-up biopsies, the b Ag persisted with HBsAg for as long as 6 years. The expression of 6 Ag showed similarities to the HBcAg system including nuclear localization, mixed nuclear cytoplasmic expression, and coexistence with anti-b in blood.
The findings are compatible with the hypothesis that b Ag represents a transmissible, defective viral agent which requires HBV as a helper and may modulate, but not terminate, ongoing HBV infection.
In 1977, Rizzetto and coworkers described 6/anti-6, a new antigen/antibody system (l), which is specifically associated with hepatitis B (HB). The delta antigen (6 Ag), a 68,000 M.W. protein (2), has been identified in liver cell nuclei of patients with chronic persistent or chronic active HB. With few exceptions (3), 8-positive cases neither express HBcAg nor HBV-like particles by matched immunohistology and electron microscopy (1, 4). Recent evidence suggests that the 6 Ag may represent superinfection of HB with a defective RNA virus (5, 6). Anti-6 is detectable only in the serum of patients with HB; it is transient and in low titers in acute HB, and persistent and in high titers in chronic HB (7). Epidemiological studies revealed a worldwide distribution of 6 Ag with a high prevalence in Italians, drugs addicts, and polytransfused HBsAg carriers (8).
In this study, we describe the cytoplasmic occurrence of 8 Ag in human liver biopsies and its preservation in formalin-fixed, paraffin-embedded liver biopsies which permits retrospective studies in stored material.