PHENOTYPING OF INTRAHEPATIC AND PERIPHERAL-BLOOD LYMPHOCYTES IN PATIENTS WITH CHRONIC HEPATITIS-C

The host immune responses have been suggested to play a role in liver injury occurring in patients with chronic hepatitis C. In order to exp lore the relationship between the relative proportions of intrahepatic and peripheral blood lymphocytes (IHL, PBL), the levels of viremia, a nd the histological hepatitis activity score, three-color fluorescence -activated cytometric analysis was performed for 36 patients with chro nic hepatitis C and six control subjects without chronic hepatitis. Th e liver biopsy was performed before any antiviral therapy. Each liver specimen was divided into two parts: one for histological examination and one for immunological analysis. Tricolor CD45 was used to improve ''lymphogating.'' Fluorescein isothiocyanate- or phycoerythrin-conjuga ted monoclonal antibodies with specificity for CD3, CD4, CD8, and CD20 (lymphocyte subpopulations), for CD69 (activated lymphocytes), and fo r CD16/56 (natural killer cells) were used. The livers of patients wit h chronic hepatitis C contained a greater proportion of CD4(+) lymphoc ytes that exhibited marked expression of CD69 than in control subjects (20.7 +/- 7.3% vs 10.2 +/- 4.6%, P = 0.027). Moreover, in patients wi th chronic hepatitis C, the proportion of CD4(+) IHL correlated with t he histological hepatitis activity evaluated by the Knodell score (r = 0.48, P = 0.004). No correlation was found between the percentage of CD4(+) IHL and the level of viremia or transaminase activities. Our fi ndings clearly indicate that a cellular immune response does take plac e in HCV-infected livers and could thus contribute to the outcome of h epatitis C virus infection.