Dynamic Changes of Monocytes and NK Cells of CHC Patient Treated by DAAs

Study Overview
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Brief Summary
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Recently,surprisingly and unexpectedly increased aggressiveness and high rates of HCC recurrence (28%(16/58) and 29%(17/59), respectively) have been reported in patients who cleared HCV with DAAs after achieving a complete response to resection or local ablation within only 6 months of therapy. The authors hypothesized that the rapid eradication of HCV and control of liver inflammation would impact anti-tumoral immune control, which in turn might contribute to the neoplastic cells proliferation. Conversely, three independent prospective French cohorts failed to reveal an increased risk of HCC recurrence after DAAs treatment in CHC patients after receiving curative cancer treatments.Although the impact of DAAs treatment on the rate of HCC occurrence or recurrence still remain unclear, it would be more important to pay attention to the immunological changes of CHC patients treated with DAAs.Up to now, little was known about the immunological changes of chronic hepatitis C (CHC) patients treated with direct-acting antiviral agents (DAAs), here we try to explore the effect of antiviral treatment of CHC patients with DAAs on the frequency of monocytes, NK cells and cytokines that promote their activation.

Detailed Description
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15 treatment-naive CHC patients and 10 healthy controls were recruited. Patients were examined before DAAs therapy (0w) and at weeks 4 (4w) and weeks 12 (12w) of the therapy. The percentage of monocytes,NK cells of the peripheral blood were analyzed by flow cytometry. Serum cytokines IL-12, IL-18, CXCL10, CXCL11, sCD14 and sCD163 were measured by enzyme linked immunosorbent assay.

Official Title
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Dynamic Changes of the Frequency of Classic and Inflammatory Monocytes Subsets and Natural Killer Cells in Chronic Hepatitis C Patients Treated by Direct-acting Antiviral Agents

Conditions
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Chronic Hepatitis C (Disorder)

Intervention / Treatment
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* Drug: Ledipasvir-Sofosbuvir
* Drug: Daclatasvir-Sofosbuvir


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CHC patients<br>15 treatment-naive CHC patients treated by Ledipasvir-Sofosbuvir orDaclatasvir-Sofosbuvir. | Drug: Ledipasvir-Sofosbuvir<br>* 8 CHC patients were treated with Sofosbuvir (400mg, qd)/Ledipasvir (90mg, qd) for 12 weeks<br>* Other names: Harvoni;Drug: Daclatasvir-Sofosbuvir<br>* 7 CHC patients were treated with Sofosbuvir (400mg, qd)/Daclatasvir (60mg,qd) for 12 weeks.<br>* Other names: Daklinza;|
| Healthy controls<br>10 Healthy controls without any treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of the frequency of CD3-CD16+CD56+ NK cells | Measurement of the frequency of CD3-CD16+CD56+ NK cells of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment) | 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of the frequency of classic CD14++CD16- monocytes and inflammatory CD14+CD16+ monocytes. | Measurement of the frequency of classic CD14++CD16- monocytes and inflammatory CD14+CD16+ monocytes of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment). | 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment) | 
| Changes of serum levels of IL-12 | Measurement of serum levels of IL-12 of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment). | 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment) | 
| Changes of serum levels of IL-18 | Measurement of serum levels of IL-18 of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment). | 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment) | 
| Changes of serum levels of CXCL10 | Measurement of serum levels of CXCL10 of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment). | 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment) | 
| Changes of serum levels of CXCL11 | Measurement of serum levels of CXCL11 of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment). | 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment) | 
| Changes of serum levels of sCD14 | Measurement of serum levels of sCD14 of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment). | 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment) | 
| Changes of serum levels of sCD163 | Measurement of serum levels of sCD163 of peripheral blood of CHC patients at 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment). | 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Monocytes, Chronic Hepatitis C, Nk cells, direct-acting antiviral agents