Microbial translocation and T cell activation are modified by direct-acting antiviral therapy in HCV-infected patients

Barbara Lattanzi, Silvia Baroncelli, Adriano De Santis, Clementina Maria Galluzzo, Gianluca Mennini, Zuleika Michelini, Marinella Lupo, Stefano Ginanni Corradini, Massimo Rossi, Lucia Palmisano, Manuela Merli

Research output: Contribution to journalArticle

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Abstract

Background: Microbial translocation from the gut lumen has been involved in the pathogenesis of liver damage in hepatitis C virus (HCV) infection. Aim: To investigate the impact of direct-acting antiviral treatment on microbial translocation and T-cell activation, in patients with hepatitis C-related liver disease. Methods: We enrolled two groups of HCV-infected patients undergoing direct-acting antiviral treatment: patients with fibrosis ≥F3 according to Metavir (Group ≥F3); patients with hepatitis C recurrence after liver transplantation and Metavir ≥F2 (Group Liver Transplantation + ≥F2). All patients were treated with direct-acting antivirals based on ongoing guidelines. Surrogate biomarkers of microbial translocation (plasma concentrations of soluble-CD14, lipopolysaccharide-binding protein and intestinal fatty acid-binding protein) were evaluated at baseline, at first month, at the end of treatment and 3 months later. T-cell activation was measured by expression of CD38+ HLA-DR at the same time points, only in Group ≥F3. Results: There were 32 patients in Group ≥F3 and 13 in Group LT + ≥F2. At baseline, levels of soluble-CD14 and lipopolysaccharide-binding protein were significantly higher in both groups vs healthy controls. Baseline soluble-CD14 correlated with glutamic-oxalacetic transaminase (r = 0.384, P = 0.009) and glutamic-pyruvic transaminase (r = 0.293, P = 0.05). A significant decrease in plasma levels of surrogate microbial translocation biomarkers was observed during and after treatment in the two groups although values were not normalised. In Group ≥F3, CD38+ HLADR+ T-cell expression was significantly decreased by direct-acting antiviral treatment. Relapsers (9%) showed higher soluble-CD14 levels at baseline. Conclusion: Surrogate microbial translocation markers and T cell activation are increased in HCV-infected patients with liver fibrosis and decrease during direct-acting antiviral treatment.

Original languageEnglish
Pages (from-to)1146-1155
Number of pages10
JournalAlimentary Pharmacology and Therapeutics
Volume48
Issue number10
DOIs
Publication statusPublished - Nov 1 2018

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Hepacivirus
Antiviral Agents
T-Lymphocytes
Hepatitis C
Liver Transplantation
Therapeutics
Biomarkers
Fatty Acid-Binding Proteins
HLA-DR Antigens
Virus Diseases
Transaminases
Alanine Transaminase
Liver Cirrhosis
Liver Diseases
Fibrosis
Guidelines
Recurrence
Liver

Keywords

  • HIV patients
  • T-cell activation
  • microbial translocation

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)

Cite this

Microbial translocation and T cell activation are modified by direct-acting antiviral therapy in HCV-infected patients. / Lattanzi, Barbara; Baroncelli, Silvia; De Santis, Adriano; Galluzzo, Clementina Maria; Mennini, Gianluca; Michelini, Zuleika; Lupo, Marinella; Ginanni Corradini, Stefano; Rossi, Massimo; Palmisano, Lucia; Merli, Manuela.

In: Alimentary Pharmacology and Therapeutics, Vol. 48, No. 10, 01.11.2018, p. 1146-1155.

Research output: Contribution to journalArticle

Lattanzi, Barbara ; Baroncelli, Silvia ; De Santis, Adriano ; Galluzzo, Clementina Maria ; Mennini, Gianluca ; Michelini, Zuleika ; Lupo, Marinella ; Ginanni Corradini, Stefano ; Rossi, Massimo ; Palmisano, Lucia ; Merli, Manuela. / Microbial translocation and T cell activation are modified by direct-acting antiviral therapy in HCV-infected patients. In: Alimentary Pharmacology and Therapeutics. 2018 ; Vol. 48, No. 10. pp. 1146-1155.
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T1 - Microbial translocation and T cell activation are modified by direct-acting antiviral therapy in HCV-infected patients

AU - Lattanzi, Barbara

AU - Baroncelli, Silvia

AU - De Santis, Adriano

AU - Galluzzo, Clementina Maria

AU - Mennini, Gianluca

AU - Michelini, Zuleika

AU - Lupo, Marinella

AU - Ginanni Corradini, Stefano

AU - Rossi, Massimo

AU - Palmisano, Lucia

AU - Merli, Manuela

PY - 2018/11/1

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N2 - Background: Microbial translocation from the gut lumen has been involved in the pathogenesis of liver damage in hepatitis C virus (HCV) infection. Aim: To investigate the impact of direct-acting antiviral treatment on microbial translocation and T-cell activation, in patients with hepatitis C-related liver disease. Methods: We enrolled two groups of HCV-infected patients undergoing direct-acting antiviral treatment: patients with fibrosis ≥F3 according to Metavir (Group ≥F3); patients with hepatitis C recurrence after liver transplantation and Metavir ≥F2 (Group Liver Transplantation + ≥F2). All patients were treated with direct-acting antivirals based on ongoing guidelines. Surrogate biomarkers of microbial translocation (plasma concentrations of soluble-CD14, lipopolysaccharide-binding protein and intestinal fatty acid-binding protein) were evaluated at baseline, at first month, at the end of treatment and 3 months later. T-cell activation was measured by expression of CD38+ HLA-DR at the same time points, only in Group ≥F3. Results: There were 32 patients in Group ≥F3 and 13 in Group LT + ≥F2. At baseline, levels of soluble-CD14 and lipopolysaccharide-binding protein were significantly higher in both groups vs healthy controls. Baseline soluble-CD14 correlated with glutamic-oxalacetic transaminase (r = 0.384, P = 0.009) and glutamic-pyruvic transaminase (r = 0.293, P = 0.05). A significant decrease in plasma levels of surrogate microbial translocation biomarkers was observed during and after treatment in the two groups although values were not normalised. In Group ≥F3, CD38+ HLADR+ T-cell expression was significantly decreased by direct-acting antiviral treatment. Relapsers (9%) showed higher soluble-CD14 levels at baseline. Conclusion: Surrogate microbial translocation markers and T cell activation are increased in HCV-infected patients with liver fibrosis and decrease during direct-acting antiviral treatment.

AB - Background: Microbial translocation from the gut lumen has been involved in the pathogenesis of liver damage in hepatitis C virus (HCV) infection. Aim: To investigate the impact of direct-acting antiviral treatment on microbial translocation and T-cell activation, in patients with hepatitis C-related liver disease. Methods: We enrolled two groups of HCV-infected patients undergoing direct-acting antiviral treatment: patients with fibrosis ≥F3 according to Metavir (Group ≥F3); patients with hepatitis C recurrence after liver transplantation and Metavir ≥F2 (Group Liver Transplantation + ≥F2). All patients were treated with direct-acting antivirals based on ongoing guidelines. Surrogate biomarkers of microbial translocation (plasma concentrations of soluble-CD14, lipopolysaccharide-binding protein and intestinal fatty acid-binding protein) were evaluated at baseline, at first month, at the end of treatment and 3 months later. T-cell activation was measured by expression of CD38+ HLA-DR at the same time points, only in Group ≥F3. Results: There were 32 patients in Group ≥F3 and 13 in Group LT + ≥F2. At baseline, levels of soluble-CD14 and lipopolysaccharide-binding protein were significantly higher in both groups vs healthy controls. Baseline soluble-CD14 correlated with glutamic-oxalacetic transaminase (r = 0.384, P = 0.009) and glutamic-pyruvic transaminase (r = 0.293, P = 0.05). A significant decrease in plasma levels of surrogate microbial translocation biomarkers was observed during and after treatment in the two groups although values were not normalised. In Group ≥F3, CD38+ HLADR+ T-cell expression was significantly decreased by direct-acting antiviral treatment. Relapsers (9%) showed higher soluble-CD14 levels at baseline. Conclusion: Surrogate microbial translocation markers and T cell activation are increased in HCV-infected patients with liver fibrosis and decrease during direct-acting antiviral treatment.

KW - HIV patients

KW - T-cell activation

KW - microbial translocation

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