Aim. Hepatitis C virus (HCV) is a major cause of post-transfusional and spo
radic hepatitis, and leads to chronic liver disease. It has been suggested
that virus-specific cytotoxic T lymphocytes are responsible for liver injur
ies that occur in HCV-infected patients. However, the detailed characterist
ics of these lymphocytes have not yet been defined. We have previously repo
rted that CD56(+) T lymphocytes, as intermediates between natural killer ce
ll and T lymphocytes, predominantly infiltrated the liver and were increase
d in patients with chronic hepatitis related to HCV (CH-C). Material and Me
thods: We obtained peripheral blood and liver tissues from 32 patients diag
nosed as having CH-C, and 10 other liver disease patients (5 chronic hepati
tis related to HBV, 5 alcoholics), and analyzed peripheral blood and liver-
infiltrating lymphocytes using flow cytometric and immunohistochemical tech
niques. Results: The CD56(+) T lymphocyte ratio in the liver of patients wi
th a high histology activity index (HAI) score for chronic hepatitis was hi
gher than that of patients with a low HAI score and patients with other liv
er diseases. In addition, T lymphocytes from patients with chronic hepatiti
s with a high HAI score carried mostly gamma delta-TCR. There was a correla
tion between the ratio of CH-C and serum alanine aminotransferase, category
I (periportal inflammation and necrosis), and IV (fibrosis) of the HAI sco
ring system. The ratio was highest in zone 1 of the hepatic lobules. Conclu
sion: The correlation between CD56+ T lymphocyte ratios and hepatocellular
damage was examined. These findings suggest strongly that liver-infiltratin
g CD56(+) T lymphocytes play an important pathologic role in hepatocellular
injury in CH-C.