Based on virological and biochemical parameters patients with chronic hepatitis B virus (HBV) are divided into distinct clinical phases: the immunetolerance phase, the immune-clearance phase, and the inactive carrier state. Unclear is whether these phases have characteristic intrahepatic immune responses. The composition of liver-derived lymphocytes in patients with chronic HBV infection was studied. In 47 patients the composition of liver-derived lymphocytes was analyzed by flow cytometry of fine needle aspiration biopsies of the liver. The proportion natural killer (NK) cells in the liver was significantly higher in immune-tolerant than in immuneclearance patients and inactive carriers. No differences were found in proportion CD4+ T-cells and CD8+ T-cells, in these phases. However, when patients in the immune-clearance phase, with similar alanine transaminase (ALT), were grouped according to viral load, the proportion CD8+ T-cells was higher in those with high viral load. In contrast, the proportion CD4+ T-cells was increased in patients with low HBV-DNA. These differences were absent in the peripheral blood (PB). Intrahepatic HBV-specific CD8+ T-cells were mainly found in immune-clearance patients with low viral load. In conclusion, clear differences in the intrahepatic cellular infiltrate were found between the various clinical phases of chronic HBV infection. These findings are relevant to the design of new, individualized anti-viral strategies.

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Journal of Medical Virology
Department of Virology

Sprengers, D, van der Molen, R.G, Kusters, J.G, Hansen, B.E, Niesters, H.G.M, Schalm, S.W, & Janssen, H.L.A. (2006). Different composition of intrahepatic lymphocytes in the immune-tolerance and immune-clearance phase of chronic hepatitis B. Journal of Medical Virology, 78(5), 561–568. doi:10.1002/jmv.20576