Regression of Human Cirrhosis.
The issue of regression of fibrosis or cirrhosis has been a subject of controversy for a long time. To my knowledge, the parameters described forming the "hepatic repair complex" do not constitute any set of accepted criteria suggestive or characteristic of anything known as "regressing cirrhosis." Statements are made by Wanless and colleagues that within the same liver, mixtures of morphologic parameters consistent with the diagnosis of complete or incomplete septal cirrhosis are observed. This is not surprising and is common knowledge among experienced morphologists who have studied a number of cases of cirrhosis large enough, irrespective of its type. These changes are most likely seen whenever necrosis and regeneration have taken place simultaneously or within a short period of time. They do not, however, constitute criteria of reversibility. The possibility that micronodular cirrhosis on biopsy converts to macronodular at autopsy is doubtful and in my view is most likely the result of sampling.
A number of the designations used by Wanless et al are new to me. The criteria used to characterize the hepatic repair complex have not been studied, to my knowledge, under other circumstances. Thus, I believe they represent the personal views of the authors; extinction lesions, accretion and resorption of collagen, large areas of extinction (multilobular necrosis?), and septa compressed by nodules leading to the resorption of collagen are all terms created by the authors and occasionally used by them before. These criteria have not, however, met with general acceptance. Is this the result of lack of reproducibility on different instances or an intrinsic characteristic of the criteria used? No answer is available.
In addition, as stated by the authors, several experimental models have provided data demonstrating the possibility of regressing cirrhosis in animal models. However, to support the hypothesis that incomplete septal cirrhosis might be at least in part the morphologic result of regressing cirrhosis, it would have been interesting to compare the features of the so-called hepatic repair complex in human liver with the morphologic aspects of regressing cirrhosis in animal livers, as described in the experimental studies on liver fibrogenesis. If frozen section material were available, the expression pattern of collagen types in the hepatic repair complex would have been interesting to study. It would be interesting to know what type of collagen expression in regions of extinction would be present following repair.
In summary, this is a highly speculative article in the interpretation of histologic findings. The pathologist will be inclined to find the statements of the authors highly difficult to accept, but certain clinicians would have the tendency to regard the business of regression of cirrhosis as quite attractive.
The mechanism of fibrogenesis is extremely complex. Several studies in humans have been done or are now in progress and are directed to test the efficacy of compounds such as colchicine, lecithin, and oxandrolone to either stop the progression of fibrosis in the liver or obtain its regression. Drugs directed to inhibit enzyme systems involved in the formation of fibrous tissue have the brightest future, but are still under investigation. The mechanisms involved in collagen formation have been the subject of investigation by several groups of basic researchers, but thus far no promising results have been obtained. In addition, some large clinical studies still in progress may provide in the near future at least the discriminating criteria that will permit the identification of distinct patient populations that may be responsive to some of the current forms of therapy under study. Reports such as the one presented here offer some hope that a cure may be achieved in the future and are suggestive that regression of fibrosis is possible.
[1.] Wanless IR, Nakashima E, Sherman M. Regression of human cirrhosis: morphologic features and the genesis of incomplete septal cirrhosis. Arch Pathol Lab Med. 2000;124:1599-1607. Accepted for publication June 2, 2000.
From the Department of Pathology, Finch University of Health Sciences, The Chicago Medical School, North Chicago, Ill.
Reprints: Finch University of Health Sciences, The Chicago Medical School, 3333 Green Bay Rd, North Chicago, IL 60064.
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|Publication:||Archives of Pathology & Laboratory Medicine|
|Date:||Nov 1, 2000|
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