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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C (Disorder)
• Intervention / Treatment: Drug: Ledipasvir-Sofosbuvir; Drug: Daclatasvir-Sofosbuvir

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 25

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Third Affiliated Hospital, Sun Yat-Sen University
• Investigators: Study Chair: Zhi-Liang Gao, Third Affiliated Hospital, Sun Yat-Sen University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: February 17, 2017
• First Submitted That Met QC Criteria: February 21, 2017
• First Posted (Actual): February 24, 2017

Study Record Updates

• Last Update Posted (Actual): February 24, 2017
• Last Update Submitted That Met QC Criteria: February 21, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Chronic Hepatitis C; Monocytes; direct-acting antiviral agents; Nk cells
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir
• Other Study ID Numbers: Effect of DAAs on immune cells

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) is not available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No