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

NCT03063723 | Completed DMC

• 1 other identifier: Effect of DAAs on immune cells
• Study Type: observational
• Target: 25
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Chronic Hepatitis C (Disorder)

Keywords

Chronic Hepatitis C; Monocytes; Nk cells; direct-acting antiviral agents

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Changes of the frequency of classic CD14++CD16- monocytes and inflammatory CD14+CD16+ monocytes.

  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

  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

  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

  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

  0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment)

Study Arms (2)

CHC patients

15 treatment-naive CHC patients treated by Ledipasvir-Sofosbuvir orDaclatasvir-Sofosbuvir.

Drug: Ledipasvir-Sofosbuvir; Drug: Daclatasvir-Sofosbuvir

Healthy controls

10 Healthy controls without any treatment

Interventions

Ledipasvir-Sofosbuvir DRUG

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

Also known as: Harvoni

CHC patients

Daclatasvir-Sofosbuvir DRUG

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

Also known as: Daklinza

CHC patients

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

15 treatment-naive CHC patients and 10 healthy controls were recruited.

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Third Affiliated Hospital, Sun Yat-Sen University: lead

Related Publications (1)

• Ning G, Li YT, Chen YM, Zhang Y, Zeng YF, Lin CS. 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. Can J Gastroenterol Hepatol. 2017;2017:3612403. doi: 10.1155/2017/3612403. Epub 2017 May 8.

  PMID: 28567369 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

peripheral blood

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

ledipasvir, sofosbuvir drug combination; daclatasvir

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Zhi-Liang Gao

  Third Affiliated Hospital, Sun Yat-Sen University

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 17, 2017
• First Posted: February 24, 2017
• Study Start: January 1, 2016
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: February 24, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share