Clinical trial NCT03210467: The Changes of Plasmacytoid Dendritic Cells Frequency and Function During Antiviral Therapy
Official title: The Changes of Plasmacytoid Dendritic Cells Frequency and Function During Pegylated Interferon α-2a and Entecavir(ETV) Treatment in Patients With Chronic Hepatitis B.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Hepatitis B Infection
Keywords: chronic hepatitis B
hepatitis B virus
Pegylated Interferon α-2a
entecavir
Plasmacytoid Dendritic Cells
Lead sponsor: Beijing Ditan Hospital
Sponsor class: OTHER
First posted: 2017-07-07
Enrollment: 120
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: the population in this study was composed of HBeAg positive chronic hepatitis B patients defined as HBsAg positive, HBeAg positive, and detectable HBVDNA load with ALT(alanine aminotransferase) level ≥190 U/L for more than 6 months.

Brief summary: Pegylated interferon(IFN) α-2a(Peg-IFN-α) not only inhibit viral replication, but also play an important role in immune regulation, while entecavir(ETV) drugs only inhibit viral replication. In hepatitis B infection, Plasmacytoid Dendritic Cells（pDCs） are the main effector cells in early antiviral innate immune response. This study was aimed at investigating the changes of pDCs frequency and function, and the expression of costimulatory molecules CD86(Cluster of Differentiation antigen 86) during Peg-IFN-αand entecavir(ETV) therapy.Meanwhile, investigators want to verify whether Peg-IFN-α suppressed the virus and the reduction of virus led to the recovery of pDCs function, or Peg-IFN-α enhanced pDCs function which gave rise to the decline of the virus.

Detailed description: Pegylated interferon α-2a(Peg-IFN-α)and entecavir(ETV) drugs can inhibit viral replication , but Peg-IFN-α also play an important role in immune regulation . In hepatitis B infection, Plasmacytoid Dendritic Cells (pDCs) are the main effector cells in early antiviral innate immune response.Peg-IFN-α recommended as the first-line treatment has a higher chance to achieve HBeAg seroconversion and even HBsAg disappearance than entecavir(ETV) drugs, which may be related to the functional activation of pDCs in the case of hepatitis and the function enhancement of pDCs during Peg-IFN-α therapy. This study was aimed at investigating the changes of pDCs frequency and function, and the expression of costimulatory molecules CD86 during Peg-IFN-αandentecavir(ETV) therapy.Meanwhile,investigators want to explore whether the decline of HBsAg and HBeAg resulted in recovery of CD86+pDC function, or recovery of CD86 + pDC function led to the decrease of HBsAg and HBeAg. Several studies demonstrated that HBsAg and HBeAg could damage pDC function, and the loss of HBsAg and HBeAg led to recovery of CD86+pDC function.

Eligibility criteria: Inclusion Criteria:

* HBsAg and HBeAg positive for more than 6 months, HBVDNA detectable with ALT(alanine aminotransferase) level abnormal lasted for three months and at least time190 IU/L or liver puncture biopsy demonstrated apparent inflammation, never treated before enrolled.

Exclusion Criteria:

* Active consumption of alcohol and/or drugs
* Co-infection with human immunodeficiency virus, hepatitis C virus, or hepatitis D virus
* History of autoimmune hepatitis
* Psychiatric disease
* Evidence of neoplastic diseases of the liver

Primary outcomes:
measure: the change of pDC%
timeFrame: after treatment 24 weeks
measure: the change of CD86+pDC%
timeFrame: after treatment 24 weeks
measure: the change of mean fluorescence intensity of costimulatory molecules CD86(CD86-MFI)
timeFrame: after treatment 24 weeks
measure: the change of absolute molecular counting of costimulatory molecules CD86
timeFrame: after treatment 24 weeks
Secondary outcomes:
measure: the change of HBVDNA levels (IU/ML)
timeFrame: after treatment 48 weeks
measure: the change of ALT levels(U/L)
timeFrame: after treatment 48 weeks
measure: the change of AST levels(U/L)
timeFrame: after treatment 48 weeks
measure: the change of HBsAg levels (IU/ML)
timeFrame: after treatment 48 weeks
measure: the change of HBeAg levels (IU/ML)
timeFrame: after treatment 48 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Ditan hospital,Capital Medical University
state: Beijing
Study officials:
References: