Hepatitis B virus replication in steroid-treated severe HBsAg-positive chronic active hepatitis

To determine the effect of corticosteroids on the replication of hepatitis B virus and to assess the relationship between virus replication and prognosis, the behavior of serum and tissue HB_cAg was evaluated in 16 patients with severe HB_sAg-positive chronic active hepatitis who were treated with prednisone and followed for up to 10 years (mean±Sem, 66±9 months). Hepatitis B virus replication was assessed in serum by a solid-phase radioimmunoassay of Dane particle-associated HB_cAg and in liver tissue by indirect immunoperoxidase staining for HB_cAg. Despite the presence of severe inflammatory activity, only low levels of hepatitis B virus replication were demonstrated. Mean serum HB_cAg levels were low at accession and remained essentially unchanged or gradually decreased during corticosteroid therapy. Serum HB_cAg appeared in only one patient in whom no virus replication was detected prior to therapy. HB_eAg was frequently detected at low titers by radioimmunoassay when serum HB_cAg was undetectable. Loss of HB_cAg preceded loss of HB_eAg by radioimmunoassay, and disappearance of both markers was a prerequisite for sustained histologic remission. In eight patients, inflammation was present despite absence of serum or tissue HB_cAg; in three of these, disease activity continued after loss of HB_eAg. We conclude that low levels of hepatitis B virus replication may be associated with severe inflammatory activity, and these levels are not increased by long-term corticosteroid therapy. Inflammation can continue despite loss of HB_eAg and absence of detectable virus replication.Presented in part at the National Meeting of the American Federation for Clinical Research, May 7, 1982, Washington, D.C.