Clinical trial NCT03188276: The Relationship Between MDSCs and NK Cells Activity of CHC Patient Treated by DAAs
Official title: The Relationship Between Direct Acting Antiviral Treatment Effect and Myeloid-Derived Suppressor Cells and NK Cells Activity in Chronic Hepatitis C
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Chronic Hepatitis C
Keywords: Chronic Hepatitis C
direct-acting antiviral agents
Myeloid-Derived Suppressor Cells
NK cells
Lead sponsor: Third Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2017-06-15
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 76
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: There are 32 treatment-naive CHC patients who treated by Ledipasvir-Sofosbuvir or Daclatasvir-Sofosbuvir.
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes of the frequency of CD14+CD11b+CD33+HLA-DR-/low MDSCs
timeFrame: 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 outcomes:
measure: Changes of the frequency of CD14+HLA-DR-/low M-MDSCs
timeFrame: 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)
measure: Changes of the frequency of CD3+CD4+ T cells
timeFrame: 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)
measure: Changes of the frequency of CD3+CD8+ T cells
timeFrame: 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)
measure: Changes of the frequency of CD3CD56+ NK cells
timeFrame: 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)
measure: Changes of the frequency of NKG2A in CD3CD56+ NK cells
timeFrame: 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)
measure: Changes of the frequency of NKp30 in CD3CD56+ NK cells
timeFrame: 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)
measure: Changes of the frequency of NKp46 in CD3CD56+ NK cells
timeFrame: 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)
Other outcomes:
Locations:
Study officials:
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
name: Zhi-liang Gao, PhD
role: STUDY_CHAIR
References: