Neutrophil function changes are associated with hemolysis in HCV patients receiving DAA treatment

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.