Background:
Bacterial infections susceptibility is known to contribute to the higher risk of mortality
of hepatitis C (HCV) patients. Deteriorated neutrophil function in HCV patients is
one of the main reasons for higher infections rate. Neutrophils recover their function
under the direct-acting antiviral (DAA) therapy; in parallel also hemolysis is reduced.
Our aim was to study if the decrease in hemolysis explains the improvement of neutrophil
function in HCV patients under DAA therapy.
Methods:
Phagocytic and respiratory burst neutrophil function and hemolysis indicators (hemoglobin,
bilirubin, hematocrit, haptoglobin and heme) were studied in 85 HCV patients (mean
age 57 ± 11 years, 40% female) before, after 12 weeks and 12 weeks after DAA therapy.
Spearman correlation with Benjamini-Hochberg correction, linear mixed model (LMM)
with likelihood ratio test (LR), ROC curve analysis in R and SPSS 23 were used to
explain the association between hemolysis and neutrophil function. The analysis was
performed accounting for confounders such as liver function, ribavirin treatment,
presence of sustained virologic response, age and sex.
Results:
At the baseline haptoglobin had a negative partial correlation with resting burst
(burst without any stimulus) and priming (burst after stimulation with fMLP). Positive
partial correlation was found between hemoglobin and phagocytic capacity. When analyzing
all time points, LMM showed that the increase in haptoglobin was associated with an
increased phagocytic capacity, a decrease in resting burst (GMFI) and a decrease in
non-phagocyting cells. The association of non-phagocyting cells, resting burst (GMFI)
and priming (GMFI) changes with haptoglobin was also shown by ROC curve analysis as
well as an association between resting burst (%) and bilirubin levels (Table 1).
Tab. 1:
The results of analysis showing the associations between neutrophil function and hemolysis
parameters
|
Partial correlation
|
LMM (LR)
|
ROC curve
|
|
Haptoglobin & Resting burst (%)
|
R =-0.231
p = 0.038
|
|
|
|
Haptoglobin & Resting burst (GMFI)
|
R =-0.238
p = 0.033
|
χ2 (1)= 4.66
p = 0.031
|
AUC = 0.652
p = 0.050
|
|
Haptoglobin & Priming (GMFI)
|
R =-0.241
p = 0.031
|
|
AUC = 0.664
p = 0.023
|
|
Haptoglobin & Phagocytic capacity
|
|
χ2 (1)= 5.65
p = 0.017
|
|
|
Haptoglobin & Non-phagocyting cells
|
|
χ2 (1)= 4.59
p = 0.032
|
AUC = 0.692
p = 0.013
|
|
Hemoglobin & Phagocytic capacity
|
R = 0.248
p = 0.025
|
|
|
|
Bilirubin & Resting burst (%)
|
|
|
AUC = 0.635
p = 0.034
|
Conclusion:
Reduction in hemolysis in DAA treated HCV patients is associated with the improvement
of their neutrophil function.
