Acute exacerbations of chronic type B hepatitis are accompanied by increased T cell responses to hepatitis B core and e antigens. Implications for hepatitis B e antigen seroconversion.

Abstract

T cell proliferative responses to hepatitis B virus-encoded envelope antigen (S + preS2 + preSj), recombinant core antigen (HBcAg), and natural hepatitis B e antigen (HBeAg) were examined in 22 HBeAg-positive patients with chronic type B hepatitis and 17 healthy hepatitis B surface antigen (HBsAg) carriers. The results showed that HBeAg-positive patients had (a) higher levels of T cell responses to HBcAg/HBeAg than those of healthy HBsAg carriers (P < 0.001 and P < 0.01, respectively); (b) a further increase in these T cell responses during acute exacerbations (P < 0.05 and P < 0.05, respectively); (c) subsidence in the T cell responses to HBcAg/HBeAg after recovery from acute exacerbations and HBeAg seroconversion, whereas the responses would persist at high levels if the patients did not enter a clinical remission; and (d) low levels of T cell responses to S + preS2 + preS, either before or after HBeAg seroconversion. The appearance of increasing T cell responses to HBcAg/HBeAg usually occurred in the early phase of acute exacerbations. These findings imply that HBcAg/HBeAg-specific T cells play an important role in the exacerbations of chronic hepatitis B and in HBeAg seroconversion. HBcAg/HBeAg-specific precursor T cell frequencies were serially studied in selected cases by limiting dilution assay. Elevation (two-to fourfold) of HBcAg/HBeAg-specific precursor T cell frequencies contributed to the increase of HBcAg/HBeAg-specific T cell proliferation during acute exacerbations. (J. Clin. Invest. 1992.89:87-96.)

Should chronic HBV infected patients with normal ALT treated: debate

“…A hallmark of this phase is flares of aminotransferases, which are believed to be manifestations of immune-mediated lysis of infected hepatocytes secondary to increased T-cell responses to hepatitis B core antigen (HBcAg) and HBeAg [2]. The duration of the ''immune-clearance'' phase, and the frequency and severity of the flares, correlate with the risk of cirrhosis and HCC.…”

Precore wild-type DNA and immune complexes persist in chronic hepatitis B after seroconversion: No association between genome conversion and seroconversion

“…However, recognition of HBcAg and HBeAg appear highly cross-reactive in terms of T-helper cell and cytotoxic T-cell (CTL) recognition. [4][5][6][7] The HBeAg, which was first described by Magnius and Espmark, 8 has been historically viewed as a marker of active viral replication. The use of serum HBeAg as a marker of viral replication was complicated by the discovery of a variant HBV lacking production of HBeAg because of various mutations within the precore region.…”

Regulation of the neutralizing anti-hepatitis B surface (HBs) antibody response in vitro in HBs vaccine recipients and patients with acute or chronic hepatitis B virus (HBV) infection

“…patients with acute hepatitis B or complete recovery from HBV infection, but none of the chronic HBV carriers, showed HBsspecific T cell responses [3,8,22,26,27]. The low rate of HBsresponsive PBMC in patients with acute HBV infection might indicate a low frequency of HBs-specific T cells in the peripheral blood.…”

“…Cytotoxic T cells recognize intracellularly processed peptide antigens that are presented by HLA class I molecules of the MHC on infected hepatocytes. These cells may be crucial for the hepatocellular damage and virus elimination in acute hepatitis B [1][2][3]. Extracellular viral antigens are bound by anti-HBs antibodies, indicating acquired immunity after viral clearance in the case of self-limited disease.…”