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

Abstract

Summary 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.

Improvement of liver disease and inflammation in patients with advanced HCV-related cirrhosis after antiviral therapy

“…In our study overall, HCV clearance after DAA therapy promoted a signi cant improvement in severity scores of liver cirrhosis and many plasma biomarkers linked to in ammation (bacterial translocation, in ammatory response, and endothelial dysfunction) and coagulopathy. Our data are in concordance with a large number of previous studies that found a signi cant decrease in liver disease scores of HIV/HCV-coinfected patients [6,7,32,[43][44][45] and HCV-monoinfected patients [6][7][8][9][10][11][12][13][14] after HCV eradiation with DAA therapy; and also in plasma biomarkers of HIV/HCV-coinfected patients [18,[30][31][32][33][34] and HCV-monoinfected patients [15][16][17][18][19][20]. However, there is an important lack of consistency in these previous publications regarding the plasma biomarkers and liver severity scores evaluated, time-points used to take data or samples after the end of HCV treatment, statistical analysis used, and liver brosis stages included.…”

“…Additionally, signi cant decreases in liver disease scores [liver stiffness measurement (LSM), hepatic venous pressure gradient (HVPG) or Child-Pugh-Turcotte (CTP)] [6][7][8][9][10][11][12][13][14] and plasma biomarkers related to in ammation and immune activation [15][16][17][18][19][20] have been described in HCV-monoinfected patients after SVR with all-oral DAAs.…”

Reversal of T Cell Exhaustion in Chronic HCV Infection

“…Most studies focused on the impact of successful DAA treatment of chronic HCV infection on the status of CD4 + and CD8 + T cell activation. While one study did not show any significant changes after treatment [99], other studies did show a decline in T cell activation status, as evidenced by reduced HLA-DR and/or CD38 expression after treatment [97,[100][101][102]. This was also demonstrated in the case of HIV-1/HCV co-infection [102].…”

Editorial: microbial translocation and immune activation profiling during treatment of chronic HCV

“…Moreover, an association of MT and fibrosis was not found also in case of portal hypertension (the presence of oesophageal varices in 41% of patients) in the Lattanzi's study . The authors inferred that it was due to the mild degree of portal hypertension in the cohort, of which only 15% had varices ≥ F2.…”

“…Specifically, data regarding the role of MT in patients with chronic hepatitis or cirrhosis related to HCV infection, either during or after HCV clearance, are still lacking. Lattanzi et al have used an elegant approach to uncover an important link between direct‐acting antiviral (DAA) treatment and its impact on MT and immune activation . The objective of the study was to evaluate the MT and immune activation changes during treatment of chronic HCV in a cohort of patients with advanced fibrosis (F3‐F4) (Group ≥F3) and patients with HCV recurrence after liver transplantation (LT) and fibrosis ≥F2 (Group LT + ≥F2).…”