The Relationship Between MDSCs and NK Cells Activity of CHC Patient Treated by DAAs

Sponsor

Third Affiliated Hospital, Sun Yat-Sen University (Other)

Overall Status

Completed

CT.gov ID

NCT03188276

Collaborator

(none)

Enrollment

Arms

14.9

Actual Duration (Months)

Study Details

Study Description

Brief Summary

Hepatitis C virus (HCV) infection is easy to chronic and can progress to cirrhosis and liver cancer. Direct-acting antiviral treatment can significantly improve the prognosis of the disease and the efficacy is seemingly not affected by a variety of viral factors. In addition, direct-acting antiviral agents therapy may affect the transformation of the immune cells and ameliorate the host immune status consequently. This study mainly investigated the relationship between Direct Acting Antiviral Treatment effect and the functional activity of myeloid-derived suppressor cells (MDSCs) and natural killer cells (NK cells) in Chronic Hepatitis C.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C	Drug: Ledipasvir-Sofosbuvir Drug: Daclatasvir-Sofosbuvir	Early Phase 1

Detailed Description

32 treatment-naive CHC patients and 20 healthy controls were recruited. Patients were examined before DAAs therapy (0w) and at weeks 4 (4w) and weeks 12 (12w) and weeks24 (24w) of the therapy. The percent age of myeloid-derived suppressor cells and NK cells of the peripheral blood were analyzed by flow cytometry. The investigators discuss the relationship between direct acting antiviral treatment effect and myeloid-derived suppressor cells and NK cells activity in chronic hepatitis C.

Study Design

Study Type:

Interventional

Actual Enrollment :

52 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Intervention Model Description:

There are 32 treatment-naive CHC patients who treated by Ledipasvir-Sofosbuvir or Daclatasvir-Sofosbuvir.There are 32 treatment-naive CHC patients who treated by Ledipasvir-Sofosbuvir or Daclatasvir-Sofosbuvir.

Masking:

None (Open Label)

Masking Description:

Thr care provider, participant, investigator and outcomes assessor all konw the process.

Primary Purpose:

Prevention

Official Title:

The Relationship Between Direct Acting Antiviral Treatment Effect and Myeloid-Derived Suppressor Cells and NK Cells Activity in Chronic Hepatitis C

Actual Study Start Date :

Feb 1, 2016

Actual Primary Completion Date :

May 1, 2017

Actual Study Completion Date :

May 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: CHC patients 32 treatment-naive CHC patients treated by Ledipasvir-Sofosbuvir or Daclatasvir-Sofosbuvir.	Drug: Ledipasvir-Sofosbuvir 15 CHC patients were treated with Sofosbuvir (400mg, qd)/Ledipasvir (90mg, qd) for 12 weeks Other Names: Harvoni Drug: Daclatasvir-Sofosbuvir 17 CHC patients were treated with Sofosbuvir (400mg, qd)/Daclatasvir (60mg,qd) for 12 weeks. Other Names: Daklinza
No Intervention: Healthy controls 20 Healthy controls without any treatment

Arm

Intervention/Treatment

Active Comparator: CHC patients

32 treatment-naive CHC patients treated by Ledipasvir-Sofosbuvir or Daclatasvir-Sofosbuvir.

Drug: Ledipasvir-Sofosbuvir

15 CHC patients were treated with Sofosbuvir (400mg, qd)/Ledipasvir (90mg, qd) for 12 weeks

Other Names:

Harvoni

Drug: Daclatasvir-Sofosbuvir

17 CHC patients were treated with Sofosbuvir (400mg, qd)/Daclatasvir (60mg,qd) for 12 weeks.

Other Names:

Daklinza

No Intervention: Healthy controls

20 Healthy controls without any treatment

Outcome Measures

Primary Outcome Measures

Changes of the frequency of CD14+CD11b+CD33+HLA-DR-/low MDSCs [0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks ( 24 weeks after DAAs treatment)]
Measurement of the frequency of CD14+CD11b+CD33+HLA-DR-/low MDSCs of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)

Secondary Outcome Measures

Changes of the frequency of CD14+HLA-DR-/low M-MDSCs [0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks ( 24 weeks after DAAs treatment)]
Measurement of the frequency of CD14+HLA-DR-/low M-MDSCs of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
Changes of the frequency of CD3+CD4+ T cells [0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks ( 24 weeks after DAAs treatment)]
Measurement of the frequency of CD3+CD4+ T cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
Changes of the frequency of CD3+CD8+ T cells [0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks ( 24 weeks after DAAs treatment)]
Measurement of the frequency of CD3+CD8+ T cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
Changes of the frequency of CD3CD56+ NK cells [0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks ( 24 weeks after DAAs treatment)]
Measurement of the frequency of CD3CD56+ NK cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
Changes of the frequency of NKG2A in CD3CD56+ NK cells [0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks ( 24 weeks after DAAs treatment)]
Measurement of the frequency of NKG2A in CD3CD56+ NK cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
Changes of the frequency of NKp30 in CD3CD56+ NK cells [0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks ( 24 weeks after DAAs treatment)]
Measurement of the frequency of NKp30 in CD3CD56+ NK cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)
Changes of the frequency of NKp46 in CD3CD56+ NK cells [0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks ( 24 weeks after DAAs treatment)]
Measurement of the frequency of NKp46 in CD3CD56+ NK cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment), 12 weeks (12 weeks after DAAs treatment) and 24 weeks (24 weeks after DAAs treatment)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 76 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Positive serum Anti-HCV antibody or serum HCV-RNA, CHC patients without any treatment

Exclusion Criteria:

Patient has a history of clinical signs/symptoms of hepatic decompensation (Child-Pugh Grade B or C) or ascites, esophageal variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis.
Patient has a history of hepatocellular carcinoma (HCC) or suspected symptoms of HCC, such as suspicious foci on imaging studies and/or serum alpha-fetoprotein (AFP)>50ng/mL.
Patient has received IFN or other immunomodulatory treatment within 52 weeks before Screening.

Patient has a medical condition that requires frequent use of systemic acyclovir or famciclovir.

Patient has a medical condition that requires frequent use of systemic corticosteroids, however topical and inhaled corticosteroids are allowed.

Patient has used hepatotoxic drugs within one month. Patient has overtaken alcohol (>40g/day) or abused illicit drugs in recent one year.

Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive urine pregnancy test.
Patients who co-infected with HAV, HBV, HDV, HEV,HIV(human immunodeficiency virus ) Patient has one or more additional known primary or secondary causes of liver disease, other than hepatitis C (e.g., alcoholism, autoimmune hepatitis).

History of malignancy of any organ system.