Myofibroblasts in the cirrhotic rat liver reflect hepatic remodeling and correlate with fibrosis and sinusoidal capillarization.

BACKGROUND/AIMS: Myofibroblasts are essential in fibrogenesis during development of cirrhosis. In the present study we stereologically quantitated MFB's and correlated them with fibrosis and sinusoidal capillarization.
METHODS: Male SD rats were rendered cirrhotic by chronic exposure to phenobarbital/CCl4, (CIR; n = 16); untreated littermates served as controls (CTR; n = 10). Sinusoidal capillarization was assessed by a multiple indicator dilution technique as previously described. The volume fractions of myofibroblasts and other liver components were estimated by morphometry.
RESULTS: Myofibroblasts averaged 15.7 +/- SD 0.7% in CIR as compared to 6.7% +/- SD 0.4% in CTR (p < 0.01). An extra-littoral compartment of myofibroblasts was found in portal tracts and within fibrous septa. In CIR, hepatocytes showed a bimodal distribution of volume fractions, and hepatocyte volume distribution disclosed a mirror image of that of myofibroblasts. Connective tissue was markedly increased in CIR, averaging 13.2 +/- 1.2% in CIR vs. 1.2 +/- 0.3% in CTR (p < 0.0001). Extravascular albumin space--a measure of sinusoidal capillarization--was reduced by 44% in CIR (0.028 +/- 0.017 vs. 0.050 +/- 0.010 ml/g; p < 0.001). The volume fraction of myofibroblasts correlated best with extravascular albumin space (r = -0.84, p < 0.001). Multiple regression analysis selected only extravascular albumin space and connective tissue to be determined by the volume fraction of myofibroblasts (r = 0.923; p < 0.001).
CONCLUSION: We conclude that increased myofibroblasts reflect the degree of hepatic remodeling rather than cirrhosis inasmuch as myofibroblast volume fraction inversely reflects that of hepatocyte bimodality. Myofibroblasts form an extra-littoral compartment in this model of CIR and correlate with hepatic fibrosis and sinusoidal capillarization.