Immunological and Virological Characterization of Patients With Chronic HBV-HDV Infection: Association With Disease Outcomes and Response to Bulevirtide Treatment
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 192
- 试验地点
- 1
- 主要终点
- Calculate the prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection naïve to treatment with Bulevirtide
研究概览
简要总结
Pharmacological, single-center, non-profit observational study.
The present study is part of a cooperation project between the SC Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Milan, Italy), the University of Milan, the University of Parma and Rome Tor Vergata, funded under the call for Research Projects of Significant National Interest - 2022 PNRR Call (Prot. P2022WEXP2).
Hepatitis D virus (HDV) is a defective RNA virus, which requires the presence of hepatitis B virus (HBV) to infect liver cells and propagate. To date, the mechanisms underlying the accelerated disease progression in the natural history of Delta hepatitis are poorly understood, as is the course of the HDV-specific immune response (CD4 and CD8 T cells). As in chronic HBV and HCV infections, the outcome of chronic HDV infection appears to be dictated primarily by the host immune response, which represents a key determinant for virus control or persistence. For HBV/HDV coinfection, the role of T cells has not been well defined, as suitable animal models are lacking and so far few HDV-specific T cell epitopes have been precisely mapped, mainly limited to HLA-B alleles.
The study is divided into two substudies (cross-sectional and longitudinal). The primary objective of the cross-sectional study is to calculate the prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection naïve to treatment with Bulevirtide. The primary objective of the longitudinal study is the change in the prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection during treatment with Bulevirtide compared to baseline (pre-treatment).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years of age or older
- •Ability to understand and sign the informed consent
- •Chronic HDV infection defined by positivity of HBsAg antigen (HBV) and HDV RNA (HBV-HDV co-infection) for at least 6 months at the time of enrollment.
排除标准
- •Co-infection with other viruses (HCV, HIV)
- •Treatment with immunosuppressive/immunomodulatory drugs
- •Other congenital and/or acquired immunodeficiency conditions
研究组 & 干预措施
Hepatis Delta in therapy
Patients with HDV cirrhosis consecutively started on Bulevirtide therapy during the study enrollment period
干预措施: Bulevirtide (Drug)
Hepatis Delta naive
Patients with HDV infection naïve to Bulevirtide therapy
结局指标
主要结局
Calculate the prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection naïve to treatment with Bulevirtide
时间窗: through study completion, an average of 2 year
Prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection naïve to treatment with Bulevirtide
Change in the prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection during treatment with Bulevirtide compared to baseline (pre-treatment)
时间窗: Month 12
Prevalence of HDV-specific T responses in patients with chronic HBV-HDV infection after 12 months of treatment with Bulevirtide compared to baseline (pre-therapy)
次要结局
- Correlate HDV-specific T cell response with stage of liver disease(through study completion, an average of 2 year)
- Analyze the role of new HBV serum biomarkers (HBcrAg, HBV RNA, HBsAg isoforms) in predicting the stage of liver disease(through study completion, an average of 2 year)
- Correlate the quantification of HDV RNA within exosomes with the stage of liver disease(through study completion, an average of 2 year)
- Investigate the correlation between the genetic heritage of HDV and the stage of liver disease(through study completion, an average of 2 year)
- Define the transcriptional and molecular signatures of CD8 T cell dysfunction in patients with chronic HBV/HDV coinfection(through study completion, an average of 2 year)
- Understanding the role of virus mutations in the virus's ability to escape CD8 T cell surveillance(through study completion, an average of 2 year)
- Correlate the prevalence of HDV-specific T cell responses with response to treatment over time(through study completion, an average of 2 year)
- Analyze the role of new HBV serum biomarkers (HBcrAg, HBV RNA, HBsAg isoforms) in predicting response to treatment with Bulevirtide;(through study completion, an average of 2 year)
- Correlate quantification of HDV RNA within exosomes with response to Bulevirtide treatment(through study completion, an average of 2 year)
- Investigate the correlation between the genetic heritage of HDV and the response to treatment with Bulevirtide(through study completion, an average of 2 year)
- Correlate the prevalence of HDV-specific T cell responses with response to treatment over time(Month 6)
- Correlate the prevalence of HDV-specific T cell responses with response to treatment over time(Month 18)