Quantitative morphometric and immunohistochemical analysis and their correlates in cirrhosis – A study on explant livers

Rókusz, András; Nagy, Eszter; Gerlei, Zsuzsanna; Veres, Dániel Sándor; Dezső, Katalin; Paku, Sándor; Szücs, Armanda; Hajósi-Kalcakosz, Szofia; Pávai, Z; Görög, Dénes; Kopper, László; Fehérvári, Imre; Nemes, Balázs; Nagy, Péter

doi:10.3109/00365521.2015.1067902

Cited by 3 publications

(3 citation statements)

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“…Therefore, although the extent of fibrosis and ductular reaction correlate, their ratio depends on the initiating event. Interestingly, we could not detect correlation between the extent of ductular reaction and etiology in human cirrhotic livers but the fibrotic area was larger in non-viral hepatitis than in viral hepatitis related cases [14], which also indicates that the ratio of ductular reaction and fibrosis varies according to the etiology. Ductular reaction can potentially contribute to fibrogenesis by transition into myofibroblasts (epithelial-to-mesenchymal transition—EMT) [28] but this aspect has not been addressed in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, our data do not support the existence of an inverse linkage between declining hepatocyte and increasing ductular proliferation during the progression of liver fibrosis. The Ki-67 index of hepatocytes and ductular reaction showed a positive correlation in advanced human cirrhotic cases [14] and Eleazar et al [13] did not find any inverse correlation between the proliferation of hepatocytes and ductular reaction in chronic hepatitis either. In our models, the expanding ductular reaction together with a declining proliferative activity do not support the regenerative role of ductular reaction during fibrosis progression.…”

Section: Discussionmentioning

confidence: 99%

“…The progenitor cell origin of regenerating hepatocytes was excluded in several experimental models applying the cre-lox based lineage tracing technique [10–12]. Others and we [13, 14] failed to determine inverse relationship between the proliferative activity of hepatocytes and ductular reaction in human cirrhotic livers. These considerations led us to perform experiments where the dynamics of fibrosis, ductular reaction and hepatocyte proliferation can be continually monitored throughout the development of cirrhosis.…”

Section: Introductionmentioning

confidence: 99%

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Ductular reaction correlates with fibrogenesis but does not contribute to liver regeneration in experimental fibrosis models

et al. 2017

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Background and aimsDuctular reaction is a standard component of fibrotic liver tissue but its function is largely unknown. It is supposed to interact with the matrix producing myofibroblasts and compensate the declining regenerative capacity of hepatocytes. The relationship between the extent of fibrosis—ductular reaction, proliferative activity of hepatocytes and ductular reaction were studied sequentially in experimental hepatic fibrosis models.MethodsLiver fibrosis/cirrhosis was induced in wild type and TGFβ overproducing transgenic mice by carbon tetrachloride and thioacetamide administration. The effect of thioacetamide was modulated by treatment with imatinib and erlotinib. The extent of ductular reaction and fibrosis was measured by morphometry following cytokeratin 19 immunofluorescent labeling and Picro Sirius staining respectively. The proliferative activity of hepatocytes and ductular reaction was evaluated by BrdU incorporation. The temporal distribution of the parameters was followed and compared within and between different experimental groups.ResultsThere was a strong significant correlation between the extent of fibrosis and ductular reaction in each experimental group. Although imatinib and erlotinib temporarily decreased fibrosis this effect later disappeared. We could not observe negative correlation between the proliferation of hepatocytes and ductular reaction in any of the investigated models.ConclusionsThe stringent connection between ductular reaction and fibrosis, which cannot be influenced by any of our treatment regimens, suggests that there is a close mutual interaction between them instead of a unidirectional causal relationship. Our results confirm a close connection between DR and fibrogenesis. However, since the two parameters changed together we could not establish a causal relationship and were unable to reveal which was the primary event. The lack of inverse correlation between the proliferation of hepatocytes and ductular reaction questions that ductular reaction can compensate for the failing regenerative activity of hepatocytes. No evidences support the persistent antifibrotic property of imatinib or erlotinib.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%