Cell-mediated hepatic injury in alcoholic liver disease. Veterans Affairs Cooperative Study Group 275.
BACKGROUND
The mechanism responsible for the initiation and perpetuation of alcoholic liver disease (ALD) remains poorly understood. This investigation attempted to elucidate the role of cell-mediated immune phenomena in the pathogenesis of ethanol-induced liver injury.


METHODS
Frozen liver biopsy specimens from 144 patients with moderate to severe ALD were examined by the avidin-biotin immunoperoxidase technique for the expression of antigenic markers of T and B lymphocytes, natural killer cells, and class I and II MHC molecules in the tissue.


RESULTS
Expression of CD3 by lymphocytes correlated significantly with regenerating nodules, intralobular inflammation, central sclerosis, and abnormalities of Kupffer cells. B cells were rarely present, and natural killer cells were absent. CD3+ lymphocytes expressed either CD4 or CD8 surface molecules. Enhanced class I MHC expression correlated significantly with portal inflammation, limiting plate erosion, vascular abnormalities, and hemosiderosis. Expression of class II MHC molecules correlated significantly with necrosis, bile stasis, and Mallory bodies.


CONCLUSIONS
The distribution and persistence of CD4+ and CD8+ cells in actively advancing ALD, the enhanced MHC expression on hepatocytes, and their relationship to alcoholic hyalin and necrosis lend support to the hypothesis that a cytotoxic T lymphocyte-hepatocyte interaction plays a role, perhaps via lymphokine production, in the genesis or perpetuation of ALD.
Department of Veterans Affairs Medical Center, Hines, Illinois.
A
A
Chedid
C L
CL
Mendenhall
T E
TE
Moritz
S W
SW
French
T S
TS
Chen
T R
TR
Morgan
G A
GA
Roselle
B A
BA
Nemchausky
C H
CH
Tamburro
E R
ER
Schiff
D017252:CD3 Complex / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007111:Immunity, Cellular; D007375:Interleukin-1 / Q000096:biosynthesis; D008099:Liver / Q000276:immunology / Q000473:pathology*; D008108:Liver Diseases, Alcoholic / Q000276:immunology* / Q000473:pathology; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D017252:CD3 Complex; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha