The
fibrosis staging criterion (Knodell's) for viral
hepatitis in human should not be applied to experimental
liver fibrosis in rodents because of differences of species and etiology.
Liver fibrosis was induced by
carbon tetrachloride (CCl(4)) or
albumin antigen-antibody complex in Balb/C mice or Wistar rats. The degree of
fibrosis was quantified by staging scores or
hydroxyproline measurement or image analysis. Inter- and intra-observer variations of the criterion were also evaluated.
Liver fibrosis was divided into seven stages: stage 0, no
fibrosis; stage 1, short fibrous tissue in central venule (C); stage 2, fibrous C-C septa appearance; stage 3, C-C fibrous septa developed incompletely; stage 4, C-C septa completely connected (pseudo-lobule); stage 5, C-P (Portal Tract) bridging
fibrosis, nodular appearance < or =50%.; and stage 6, nodular appearance >50%. There was significant correlation between the staging scores and
hydroxyproline concentration (r = 0.708 in mice, r = 0.841 in rats) and, between staging scores and
fibrosis area (r = 0.919 in rats, P < 0.001). The interobserver and intraobserver agreement was consistent (kappa = 0.738 or 0.726, P < 0.001). This staging of hepatic
fibrosis in rodents is scientifically rational and repeatable, and is therefore suggested as the criterion for the assessment of experimental hepatic
fibrosis in rodent studies.