INFLAMMATORY MARKERS IN CHRONIC HEPATITIS-C

To test the hypothesis that inflammation in hepatitis C follows mechan isms common to immune-activated pathways, the distributions of T and B cells, adhesion molecules and transforming growth factor-beta (TGF-be ta) were assessed in liver biopsies with chronic inflammation due to h epatitis C (HCV, n=8) and other causes (non-HCV, n=10). Frozen section s were immuno-stained using primary antibodies to CD2, CD20, CD4, CD8, intercellular adhesion molecule (ICAM-1), vascular cell adhesion mole cule (VCAM)-1, HLA-DR, lymphocyte function-associated antigen (LFA)-1, and TGF-beta. Inflammatory cells positive for each immunophenotypic m arker were counted, and positive staining for adhesion molecules, HLA- DR and TGF-beta was graded in triads and lobules and compared in HCV a nd non-HCV biopsies. In all biopsies, T cells were more frequent than B cells, both in triads and lobules. CD20+, CD4+, CD8+ and LFA-1+ cell s were increased in HCV compared to non-HCV biopsies. Portal lymphoid aggregates were present in 6 of 8 HCV biopsies and 3 of 10 non-HCV bio psies. Aggregates consisted of CD20+, CD4+, CD8+ and LFA-1+ cells, and ICAM-1 and VCAM-1 were increased. Sinusoidal lining cells in HCV biop sies and non-HCV biopsies with inflammation expressed HLA DR, ICAM-1, and CD4. TGF-beta was increased in foci of necrosis. Inflammation in c hronic HCV involves common immune-mediated cellular effector pathways and the inflammation in the portal triads represents aggregation of bo th T and B cells, mediated in part by upregulation of adhesion molecul es on portal stromal cells; this is possibly in response to antigens d raining from necroinflammatory foci in the lobules. TGF-beta is increa sed in active necroinflammatory foci, but not in portal lymphoid aggre gates.