Abstract
Recognition of HBV‐infected hepatocytes by CD8 T‐lymphocytes is important for viral clearance. Expression of hepatitis B core antigen (HBcAg) in HBV‐infected hepatocytes can trigger this antiviral T‐cell response. The intrahepatic CD8 T‐lymphocytes and HBcAg expression were investigated in relation to response to antiviral therapy. Forty chronic HBeAg‐positive patients treated with either lamivudine (n = 20) or interferon‐alpha (n = 20) were investigated. Ten patients from each treatment group exhibited a response. Liver biopsies were carried out before and after therapy. CD8 T‐lymphocytes and HBcAg expression were detected by immunohistochemistry. The number of pretreatment intrahepatic CD8 T‐lymphocytes was significantly higher in responders (P = 0.008). In responders baseline nuclear HBcAg expression tended to be lower (P = 0.09). Cytoplasmic expression was not significantly different between responders and non‐responders (P = 0.46). The number of CD8 T‐lymphocytes correlated with cytoplasmic HBcAg (r~s~ = 0.31; P = 0.04); CD8 T‐lymphocytes were situated in clusters of hepatocytes with cytoplasmic HBcAg. Longitudinal analysis showed a significant reduction of CD8 T‐lymphocytes after treatment in responders (P < 0.001). Multivariate analysis revealed pretreatment CD8 T‐lymphocytes and age as independent prognostic factors for response (n = 40). The number of pretreatment CD8 T‐lymphocytes was the only independent prognostic indicator for response to interferon‐alpha (P = 0.03); it was of borderline significance for lamivudine therapy (P = 0.06). It is concluded that the number of pretreatment intrahepatic CD8 T‐lymphocytes is an important predictor of response to HBV therapy with either interferon‐alpha or lamivudine. Response to therapy led to a significant reduction of intrahepatic CD8 T‐lymphocytes. Co‐localisation of CD8 T‐lymphocytes and HBcAg‐positive hepatocytes suggests antiviral activity predominantly at the site of maximum HBV replication. J. Med. Virol. 72:215–222, 2004. © 2004 Wiley‐Liss, Inc.