title: Intrahepatic CD8 T-lymphocytes and HBV core expression in relation to response to antiviral therapy for chronic hepatitis B patients.
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.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
authors.forename: Thjon J
authors.initials: TJ
authors.lastname: Tang
authors.forename: Robert A
authors.initials: RA
authors.lastname: de Man
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Kusters
authors.forename: Jaap
authors.initials: J
authors.lastname: Kwekkeboom
authors.forename: Wim C J
authors.initials: WC
authors.lastname: Hop
authors.forename: Renate G
authors.initials: RG
authors.lastname: van der Molen
authors.forename: Solko W
authors.initials: SW
authors.lastname: Schalm
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
mesh_terms: D000293:Adolescent; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006512:Hepatitis B Core Antigens / Q000378:metabolism*; D006515:Hepatitis B virus / Q000187:drug effects / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D008099:Liver / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006512:Hepatitis B Core Antigens; D016898:Interferon-alpha; D019259:Lamivudine