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Inflammation response and liver stiffness: predictive model of regression of hepatic stiffness after sustained virological response in cirrhotics patients with chronic hepatitis C

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Abstract

Cirrhotic patients with chronic hepatitis C should be monitored for the evaluation of liver function and screening of hepatocellular carcinoma even after sustained virological response (SVR). The stage of inflammatory resolution and regression of fibrosis is likely to happen, once treatment and viral clearance are achieved. However, liver examinations by elastography show that 30–40% of patients do not exhibit a reduction of liver stiffness. This work was a cohort study in cirrhotic patients whose purpose was to identify immunological factors involved in the regression of liver stiffness in chronic hepatitis C and characterize possible serum biomarkers with prognostic value. The sample universe consisted of 31 cirrhotic patients who underwent leukocyte immunophenotyping, quantification of cytokines/chemokines and metalloproteinase inhibitors in the pretreatment (M1) and in the evaluation of SVR (M2). After exclusion criteria application, 16 patients included were once more evaluated in M3 (like M1) and classified into regressors (R) or non-regressors (NR), decrease or not ≥ 25% stiffness, respectively. The results from ROC curve, machine learning (ML) and linear discriminant analysis showed that TCD4 + lymphocytes (absolute) are the most important biomarkers for the prediction of the regression (AUC = 0.90). NR patients presented levels less than R of liver stiffness since baseline, whereas NK cells were increased in NR. Therefore, it was concluded that there is a difference in the profile of circulating immune cells in R and NR, thus allowing the development of a predictive model of regression of liver stiffness after SVR. These findings should be validated in greater numbers of patients.

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Funding

The project was carried out with the financial support of FAPESP, process 2016/25416-3, and Coordination for the Improvement of Higher Education Personnel – Brazil (CAPES)—Funding Code 001 (grants).

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Authors and Affiliations

  1. Graduate Program in Pathophysiology in Clinical Medicine, Department of Clinical Medicine, São Paulo State University (UNESP), Botucatu Medical School, Botucatu, São Paulo, Brazil

    Aline Márcia Marques Braz, Fernanda Cristina Winckler & Giovanni Faria Silva

  2. Flow Cytometry Laboratory, Applied Biotechnology Laboratory - LBA, Clinical Hospital of Botucatu Medical School, Av. Prof. Mário Rubens Guimarães Montenegro, s/n, Botucatu, São Paulo, Brazil

    Aline Márcia Marques Braz, Larissa Sarri Binelli, Luis Guilherme Chimeno, Lia Beatriz Mantovani Lopes & Marjorie de Assis Golim

  3. Graduate Program in Research and Development (Medical Biotechnology, São Paulo State University (UNESP), Botucatu Medical School, Botucatu, São Paulo, Brazil

    Luis Guilherme Chimeno, Lia Beatriz Mantovani Lopes, Rafael Plana Simões, Rejane Maria Tommasini Grotto, Marjorie de Assis Golim & Giovanni Faria Silva

  4. Graduate Program in Pathology, Department of Pathology, São Paulo State University (UNESP), Botucatu Medical School, Botucatu, São Paulo, Brazil

    Rodrigo Santos Lima & Rejane Maria Tommasini Grotto

  5. Department of Biotechnology and Bioprocess Engineering, São Paulo State University (UNESP), Faculty of Agronomic Sciences, Botucatu, São Paulo, Brazil

    Rafael Plana Simões & Rejane Maria Tommasini Grotto

  6. Molecular Biology Laboratory, Applied Biotechnology Laboratory - LBA, Clinical Hospital of Botucatu Medical School, Botucatu, São Paulo, Brazil

    Rejane Maria Tommasini Grotto

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  1. Aline Márcia Marques Braz
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  2. Fernanda Cristina Winckler
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  3. Larissa Sarri Binelli
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  4. Luis Guilherme Chimeno
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Contributions

AMMB, RPS, MAG, and GFS were involved in conceptualization. AMMB, FCW, RPS, MAG, and GFS were involved in data curation. AMMB, RPS, MAG, and GFS were involved in formal analysis. AMMB, RPS, MAG, and GFS were involved in investigation. AMMB, FCW, LSB, LGC, LBML, RPS, MAG, and GFS were involved in methodology. MAG and GFS were involved in supervision. AMMB, AMMB, RSL, RPS, RMTG, MAG, and GFS were involved in writing—original draft. AMMB, RSL, RMTG, MAG, and GFS were involved in writing—review and editing.

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Correspondence to Marjorie de Assis Golim.

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This study was approved by the Research Ethics Committee of Botucatu Medical School, UNESP (protocol no. 2.810.759).

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Braz, A.M.M., Winckler, F.C., Binelli, L.S. et al. Inflammation response and liver stiffness: predictive model of regression of hepatic stiffness after sustained virological response in cirrhotics patients with chronic hepatitis C. Clin Exp Med 21, 587–597 (2021). https://doi.org/10.1007/s10238-021-00708-w

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