During progression from normal liver to
cirrhosis, total
collagen increases nearly 10-fold with an abnormal increase in fibril-forming
collagen and other extracellular matrix molecules. However, little is known regarding the changes each
collagen type undergoes during fibrogenesis. We assessed the different
collagen types by immunohistochemistry at various stages of
hepatitis C-related
liver fibrosis in core biopsies and compared changes in each with
trichrome stain to better understand fibrogenesis. The possible utility in staging
fibrosis was investigated. We found
collagens III, IV, V, VI,
vitronectin, and trichrome all showed statistically significant increases from early to late stages of
fibrosis, but with temporal and quantitative differences. During the transition from early to late
fibrosis, trichrome (stains primarily
collagen I) and
collagen IV showed the steepest increase and appear to be the most useful discriminators between early and late stages of
fibrosis.
Collagens V and VI have strong reactivity even in stage 1, which may be helpful in identifying early
fibrosis when trichrome is weak or negative.
Collagen III and
vitronectin showed the most gradual increase. Interestingly,
collagen V also showed increased staining in areas around
inflammation/
edema, which may overestimate established
fibrosis as compared with trichrome.