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Recovery of natural killer cells is mainly in post-treatment period in chronic hepatitis C patients treated with sofosbuvir plus ledipasvir.

ABSTRACT: AIM:To investigate how natural killer (NK) cells are affected in the elimination of hepatitis C virus (HCV) by sofosbuvir/ledipasvir, two highly effective direct-acting antivirals (DAAs). METHODS:Thirteen treatment-naïve and treatment-experienced chronic hepatitis C (CHC) patients were treated with sofosbuvir/ledipasvir, and NK cells were detected at baseline, weeks 2, 4, 8 and 12 during therapy, and week post of treatment (Pt)-12 and 24 after the end of therapy by multicolor flow cytometry and compared with those from 13 healthy controls. RESULTS:All patients achieved sustained virological response. There was a significant decline in CD56bright NK cell frequencies at week 8 (P = 0.002) and week 12 (P = 0.003), which were altered to the level comparable to healthy controls at week Pt-12, but no difference was observed in the frequency of CD56dim NK cells. Compared with healthy controls, the expression levels of NKG2A, NKp30 and CD94 on NK cells from CHC patients at baseline were higher. NKG2A, NKp30 and CD94 started to recover at week 12 and reached the levels similar to those of healthy controls at week Pt-12 or Pt-24. Before treatment, patients have higher interferon (IFN)-? and perforin levels than healthy controls, and IFN-? started to recover at week 8 and reached the normalized level at week Pt-12. CONCLUSION:NK cells of CHC patients can be affected by DAAs, and phenotypes and function of NK cells recover not at early stage but mainly after the end of sofosbuvir/ledipasvir treatment.

SUBMITTER: Wang XX

PROVIDER: S-EPMC6209576 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

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Recovery of natural killer cells is mainly in post-treatment period in chronic hepatitis C patients treated with sofosbuvir plus ledipasvir.

Wang Xiao-Xiao XX Luo Bi-Fen BF Jiang Han-Ji HJ Cong Xu X Jin Qian Q Ma Dan-Li DL Wei Lai L Feng Bo B

World journal of gastroenterology 20181001 40

<h4>Aim</h4>To investigate how natural killer (NK) cells are affected in the elimination of hepatitis C virus (HCV) by sofosbuvir/ledipasvir, two highly effective direct-acting antivirals (DAAs).<h4>Methods</h4>Thirteen treatment-naïve and treatment-experienced chronic hepatitis C (CHC) patients were treated with sofosbuvir/ledipasvir, and NK cells were detected at baseline, weeks 2, 4, 8 and 12 during therapy, and week post of treatment (Pt)-12 and 24 after the end of therapy by multicolor flow ...[more]

PMID: 30386105

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Project description:Chronic hepatitis C virus (HCV) infection is characterized by dysregulated natural killer (NK) cell responses. NKs play a critical role in achieving sustained responses to interferon (IFN)-?-based therapy. Rapid sustained HCV-RNA clearance is now achieved with direct-acting antivirals (DAAs). Studies of patients receiving first-wave DAAs suggest NK functional restoration. Here, we investigate the effect of mainstream DAA treatment on NKs. We collected a prospective cohort of male HCV genotype 1-infected patients treated with ledipasvir/sofosbuvir (n = 22). Peripheral blood was obtained at treatment start, week 2 (W2), W4, W8, and W12 of treatment and 12 weeks posttreatment. Flow cytometry was used to characterize NK responses to therapy. Mean baseline viral load was 1.75 million IU/mL. All subjects rapidly cleared virus and remained HCV RNA-negative posttreatment. No change was seen in total NK levels; however, the frequency of immature NKs (clusters of differentiation [CD]56bright) decreased by W2 and was maintained throughout the study. Phenotypic changes were evident by W2/W4, coincident with rapid viral clearance. At W2, T-cell immunoglobulin and mucin-domain containing-3 and CD161 were significantly increased, returning to pretreatment levels by W12. Some changes were not evident until late (W12 or posttreatment). Down-regulation of several activation markers, including NKp30 and tumor necrosis factor-related apoptosis-inducing ligand, was observed at W12 and sustained posttreatment. No difference was observed in IFN-? production or cytokine-mediated killing of NK-sensitive cell line K562 posttreatment compared to pretreatment. Conclusion: Our phenotype data suggest transient activation followed by dampening of NK cell activity to pretreatment levels. The NK response to ledipasvir/sofosbuvir is not universal in a homogeneous patient cohort. More studies are needed to elucidate the roles of NK cells in IFN-free regimens, which will have implications for protection from re-infection and fibrosis progression. (Hepatology Communications 2018;2:364-375).

Dataset Information

Recovery of natural killer cells is mainly in post-treatment period in chronic hepatitis C patients treated with sofosbuvir plus ledipasvir.

Publications

Recovery of natural killer cells is mainly in post-treatment period in chronic hepatitis C patients treated with sofosbuvir plus ledipasvir.

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