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临床试验/NCT04170452
NCT04170452Unknown不适用

HBV DNA Replication in Hepatocytes in HBV and HDV Co-infection

Tokhirbek Dolimov1 个研究点 分布在 1 个国家目标入组 30 人开始时间: 2019年10月10日最近更新:
适应症

试验速览

阶段
不适用
发起方
入组人数
30
试验地点
1
主要终点
The study the content of the HBV DNA in liver biopsy

研究概览

简要总结

Study the content of the HBV DNA in liver biopsy in the patients with the Chronic Hepatitis Delta in absence of the HBV DNA in the blood plasma

详细描述

Investigators interpreted the data of several researchers that studied suppression of the HBV DNA replication in the Delta infection within this article. Co-infection and superinfection of hepatitis B virus (HBV) with hepatitis delta virus (HDV) leads to suppression of HBV replication in both patients as well as animals and cell models. The mechanisms underlying this suppression were not fully studied before.

Jaw-Ching Wu et al. described the suppression of HBV DNA replication during HBV and HDV co-infection for the first time in 1991. The results of studies in the liver experimental models HuH-7 clearly demonstrated that one delta HDV antigen can suppress the expression of HBV RNA.

Dulce Alfaiate et al. conducted studies on the experimental models proving that HBV replication markers, including HBeAg, total HBV DNA and pregenomic RNA were significantly reduced after superinfection with HDV which confirming the effect of HDV on HBV. But thereby, the levels of circularly covalently closed levels of HBV DNA (cccDNA) and HBsAg were not decreased. At the peak of HDV-RNA accumulation and appearance of the interference in HBV replication, a strong I type IFN response was observed with highly induced genes stimulated by the interferon, RSAD2 (Viperin) and IFI78 (MxA). Both mono- and superinfected dHepaRG cells maintained strong intracellular replication of HDV, which was accompanied with the strong secretion of infectious HDV virions.

The following analysis of the data in the experimental studies by Zhenfeng Zhang et al. proved that the HDV virus activated strongly IFN-β and IFN-λ in the hepatocyte cell lines. The active HDV replication induces the IFN-β/λ response. Unlike hepatitis B virus, hepatitis D virus infection causes a strong IFN-β/λ response in the innate immunocompetent cell lines. The activated IFN did not suppress replication of hepatitis D virus in vitro, which indicatesthat Delta hepatitis virus is resistant to the self-induced innate immune responses and therapeutic treatment for IFN.

According to the authors, this stimulation of the synthesis of endogenous IFN-β and IFN-λ inside the hepatocyte by the HDV virus caused suppression of the HBV virus replication.

研究设计

研究类型
Observational
观察模型
Cohort
时间视角
Prospective

入排标准

年龄范围
18 Years 至 40 Years(Adult)
性别
All
接受健康志愿者

入选标准

  • patients with the Chronic Hepatitis Delta in absence of the HBV DNA in the blood plasma

排除标准

  • patient's with the Chronic Hepatitis Delta in absence of the HBV DNA in the blood plasma but: inability to remain still and to maintain brief expiration for the procedure, suspected vascular lesion (eg, hemangioma), bleeding tendency (eg, INR > 1.2 despite receiving vitamin K, bleeding time > 10 min), severe thrombocytopenia (< 50,000/mL)

结局指标

主要结局

The study the content of the HBV DNA in liver biopsy

时间窗: up to 3 months

In this study we are going to do liver biopsy in 30 patients with a diagnosis of Chronic Viral Hepatitis B and Delta.

次要结局

未报告次要终点

研究者

发起方
Tokhirbek Dolimov
申办方类型
Other Gov
责任方
Sponsor Investigator
主要研究者

Tokhirbek Dolimov

Research Institute of Epidemiology, Microbiology and Infectious deseases

Research Institute of Epidemiology, Microbiology and Infectious Diseases, Uzbekistan

研究点 (1)

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