Stromal mast cells and nerve fibers in various chronic liver diseases: relevance to hepatic fibrosis

Abstract

OBJECTIVE: Recently, mast cells have been postulated to play a role in fibrogenesis in primary biliary cirrhosis (PBC) and alcoholic liver disease (ALD). There are only a few reports on nerve fibers in normal and pathological human livers. METHODS: We simultaneously investigated mast cells and nerve fibers in the stroma by single and double immunostainings and by quantitative morphometry in six normal livers and in 178 liver biopsies of PBC (n = 49), autoimmune hepatitis (n = 12), chronic hepatitis B (n = 37), chronic hepatitis C (n = 41), and ALD (n = 39). RESULTS: The densities of tryptase-positive mast cells, chymase-positive mast cells, and S-100-positive nerve fibers in the stroma were significantly higher in these chronic liver diseases than in normal livers. There were no significant differences in their densities among these chronic liver diseases. The densities of tryptase- and chymase-positive mast cells correlated significantly with degree of fibrosis, and density of nerve fibers correlated roughly with degree of fibrosis. Double immunostainings showed that some mast cells were in close contact with nerve fibers, and that, in selected cases, the percentages of mast cells positive for only tryptase (MC T) and those positive for both tryptase and chymase (MC TC) were 26% and 74%, respectively. CONCLUSIONS: These results suggest that mast cells and nerve fibers are involved in fibrogenesis in chronic liver diseases, regardless of their etiologies, probably by secreting fibrogenic substances. Some mast cells are innervated, and this innervation may stimulate mast cells to secrete fibrogenic substances, leading to hepatic fibrosis.