Clinical trial NCT03063723: Dynamic Changes of Monocytes and NK Cells of CHC Patient Treated by DAAs
Official title: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Hepatitis C (Disorder)
Keywords: Chronic Hepatitis C
Monocytes
Nk cells
direct-acting antiviral agents
Lead sponsor: Third Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2017-02-24
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 15 treatment-naive CHC patients and 10 healthy controls were recruited.

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.

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.

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 CD3-CD16+CD56+ NK cells
timeFrame: 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment)
Secondary outcomes:
measure: Changes of the frequency of classic CD14++CD16- monocytes and inflammatory CD14+CD16+ monocytes.
timeFrame: 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment)
measure: Changes of serum levels of IL-12
timeFrame: 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment)
measure: Changes of serum levels of IL-18
timeFrame: 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment)
measure: Changes of serum levels of CXCL10
timeFrame: 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment)
measure: Changes of serum levels of CXCL11
timeFrame: 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment)
measure: Changes of serum levels of sCD14
timeFrame: 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment)
measure: Changes of serum levels of sCD163
timeFrame: 0 week (before DAAs treatment),4 weeks (4 weeks after DAAs treatment) and 12 weeks (12 weeks after DAAs treatment)
Other outcomes:
Locations:
Study officials:
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
name: Zhi-Liang Gao
role: STUDY_CHAIR
References:
citation: 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.