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TGF-beta and mesenchymal hepatic involvement after visceral leishmaniasis

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Abstract

The liver involvement in the human visceral leishmaniasis (VL) has been related to parasitism and activated Kupffer cells with further occasional fibrotic alterations, especially after long-term disease without treatment. However, fibrotic alterations have been reported after therapy, whose clinical finding is the persistence of hepatomegaly. Fibrotic involvement of the liver after therapy was never well understood, and the aim of this study was to evaluate this finding through ultrastructural and morphometric analysis. A case–control study was performed with 20 patients (15 cases and five controls). Cases included patients with persistent hepatomegaly (residual) after treatment of VL submitted to liver biopsy to exclude other causes of liver enlargement, including serum tests of viral hepatitis. The material was evaluated by electron microcopy allowing ultrastructural with morphometric analysis of medium portion of hepatic lobule. Narrow sinusoidal lumen and prominent Kupffer cells were found with insignificant alterations of hepatocytes, pit, and endothelial cells. On ultrastructural analysis, the enlargement of the space of Disse was due to fibrous collagen, increase of number of Ito cells, and nonfibrous extracellular matrix that were associated with Kupffer cells enlargement. Immunohistochemistry showed an intense expression of TGF-beta in patients with VL. These findings suggest a production of TGF-beta by Kupffer cells that resulted in the characteristic fibrotic involvement of the liver. Residual hepatomegaly in visceral leishmaniasis could result from sustained Kupffer cell activation with perihepatocytic fibrosis.

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Authors and Affiliations

  1. Laboratory of the Discipline of Pathology of Transmissible Disease, University of Sao Paulo, Faculty of Medical Sciences, Av. Dr.Arnaldo, 455-Cerqueira César, 01246-903, São Paulo, SP, Brazil

    Maria Irma Seixas Duarte, Heitor Franco de Andrade Jr., Cleusa Fumica Hirata Takamura & Antonio Sesso

  2. Laboratory of Protozoology, Tropical Medicine Institute of São Paulo, University of São Paulo, Faculty of Medical Sciences, São Paulo, SP, Brazil

    Heitor Franco de Andrade Jr.

  3. Department of Infectious Diseases, University of Sao Paulo, Faculty of Medical Sciences, São Paulo, Brazil

    Felipe Francisco Tuon

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  1. Maria Irma Seixas Duarte
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  2. Heitor Franco de Andrade Jr.
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  3. Cleusa Fumica Hirata Takamura
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  4. Antonio Sesso
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  5. Felipe Francisco Tuon
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Correspondence to Felipe Francisco Tuon.

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The authors are not part of any associations or commercial relationships that might represent conflicts of interest in the writing of this study (e.g., pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding). This article has financial support by the FAPESP (Grants 96/5875-8)

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Duarte, M.I.S., de Andrade, H.F., Takamura, C.F.H. et al. TGF-beta and mesenchymal hepatic involvement after visceral leishmaniasis. Parasitol Res 104, 1129–1136 (2009). https://doi.org/10.1007/s00436-008-1298-4

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  • DOI: https://doi.org/10.1007/s00436-008-1298-4

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