ABSTRACT
Advanced liver fibrosis is generally considered to be irreversible. We studied the reversibility of marked liver fibrosis in rabbits infected with Schistosoma japonicum. We determined liver collagen content, collagen biosynthesis, and collagenase activity using serial biopsy specimens obtained 20, 40, and 60 weeks after infection. Reversibility of this process was investigated in rabbits cured of infection at 21 weeks; control rabbits not cured of infection were also studied. At 20 weeks, liver collagen content was 16-fold greater than normal, with accumulation of collagen types I, III, and V. Synthesis of collagen within fibrotic liver slices was 10-fold greater than normal. Liver collagenolytic activity for a type I substrate was 19-fold greater than normal. After parasitologic cure, a striking morphologic reversal of fibrosis occurred during the subsequent 40 weeks, with the return of liver collagen content to three-fold greater than normal and a 75% decrease in synthetic rates compared with those at 20 weeks (P < 0.01). Collagenolytic activity remained elevated to the same degree noted at 20 weeks. A similar but lesser resolution of fibrosis also occurred in untreated control rabbits, coincident with a spontaneous decrease in new egg deposition known to occur in this model system. We conclude that advanced liver fibrosis in S. japonicum-infected rabbits is slowly reversible after cure or senescence of the infection. A possible mechanism for this reversal is persistently increased collagenolysis as collagen synthesis diminishes.
Subject(s)
Liver Cirrhosis/etiology , Liver/pathology , Schistosomiasis japonica/complications , Animals , Collagen/analysis , Collagen/biosynthesis , Collagen/metabolism , Collagenases/metabolism , Diphenylamine/analogs & derivatives , Diphenylamine/therapeutic use , Isothiocyanates/therapeutic use , Liver/chemistry , Liver/parasitology , Liver Cirrhosis/pathology , Male , Parasite Egg Count , Rabbits , Schistosoma japonicum/growth & development , Schistosomiasis japonica/drug therapy , Schistosomiasis japonica/pathology , Schistosomicides/therapeutic useABSTRACT
Colorectal cancer is the second most common cause of cancer in the United States. The overall mortality rate approaches 60%. However, the detection of early lesions results in a mortality rate of 20% or less. Therefore, if improvement in survival is to occur, increased efforts need to be focused not only on primary prevention but also on early detection of malignant lesions and the eradication of potentially malignant lesions. There is no universal consensus as to how this can be accomplished. The purpose of this article is to serve as a guideline, providing a practical basis for improving early detection and management of colorectal cancer and its precursors.
