Phenotyping of intrahepatic and peripheral blood lymphocytes in patients with chronic hepatitis C.

The host immune responses have been suggested toplay a role in liver injury occurring in patients withchronic hepatitis C. In order to explore therelationship between the relative proportions ofintrahepatic and peripheral blood lymphocytes (IHL, PBL),the levels of viremia, and the histological hepatitisactivity score, three-color fluorescence-activatedcytometric analysis was performed for 36 patients with chronic hepatitis C and six control subjectswithout chronic hepatitis. The liver biopsy wasperformed before any antiviral therapy. Each liverspecimen was divided into two parts: one forhistological examination and one for immunological analysis.Tricolor CD45 was used to improve“lymphogating.” Fluorescein isothiocyanate-or phycoerythrin-conjugated monoclonal antibodies withspecificity for CD3, CD4, CD8, and CD20 (lymphocyte subpopulations),for CD69 (activated lymphocytes), and for CD16/56(natural killer cells) were used. The livers of patientswith chronic hepatitis C contained a greater proportion of CD4+ lymphocytes that exhibitedmarked expression of CD69 than in control subjects (20.7± 7.3% vs 10.2 ± 4.6%, P = 0.027).Moreover, in patients with chronic hepatitis C, theproportion of CD4+ IHL correlated with the histological hepatitisactivity evaluated by the Knodell score (r = 0.48, P =0.004). No correlation was found between the percentageof CD4+ IHL and the level of viremia ortransaminase activities. Our findings clearly indicate thata cellular immune response does take place inHCV-infected livers and could thus contribute to theoutcome of hepatitis C virus infection.