Sequencing-Based Tracking of Entecavir Resistance-Associated Mutations in Chronic Hepatitis B Patients: A Multicenter Observational Study (STREAM)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 700
- 试验地点
- 1
- 主要终点
- Prevalence of entecavir resistance-associated mutations in the HBV polymerase/RT region detected by Oxford Nanopore sequencing.
研究概览
简要总结
Chronic hepatitis B is a long-term viral infection that affects millions of people worldwide. Patients usually require lifelong antiviral treatment to control the virus and prevent liver damage.
Some older antiviral medications, such as lamivudine, can lead to the development of viral resistance. This means the virus changes in a way that makes certain treatments less effective. Even though newer drugs like entecavir are stronger and more resistant to these changes, previous exposure to lamivudine may increase the risk of developing additional resistance mutations.
By analyzing viral genetic material from blood samples using advanced sequencing technology, this research will help improve understanding of antiviral resistance patterns in patients with chronic hepatitis B in Turkey and may support better treatment decisions in the future.
详细描述
Hypothesis
- Entecavir resistance-associated mutations are detectable in both naïve and lamivudine-experienced patients.
- Prevalence is higher in lamivudine-experienced patients compared to treatment-naïve patients.
- Longer lamivudine exposure and higher HBV-DNA are associated with resistance.
- Nanopore sequencing detects minor resistance variants not captured by conventional methods.
Sample size: 700 estimated participants
Pre-existing lamivudine-induced resistance mutations create a genetic background that facilitates the emergence of secondary entecavir resistance mutations, even in patients currently receiving tenofovir-based therapy.
Investigators further hypothesize that peripheral blood-derived cccDNA sequencing can serve as a minimally invasive method to characterize transmitted and acquired resistance mutation profiles in chronic HBV infection.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •HBsAg positive
- •Group 1: Either treatment-naïve participants with HBV DNA>2000 IU/ml
- •Group 2: Prior lamivudine therapy ≥6 months with switch to ADVor TDF or TAF
- •Ability to provide informed consent
排除标准
- •Prior entecavir exposure
- •Prior telbivudine exposure
- •Age <18 years
- •Inability to provide informed consent Note: Previous adefovir or (pegylated) interferon use is not an exclusion criterion.
- •Patients with insufficient sample volume or inadequate DNA quality for sequencing will be excluded from final analysis.
研究组 & 干预措施
Treatment-Naïve Chronic HBV Patients
Adult (≥18 years) HBsAg-positive patients with HBV-DNA >2,000 IU/mL who have not received prior nucleos(t)ide analogue therapy.
干预措施: Viral genetic material from blood samples using advanced sequencing technology (Diagnostic Test)
Lamivudine-Experienced Chronic HBV Patients
Adult (≥18 years) HBsAg-positive patients with a documented history of lamivudine therapy for ≥6 months who were subsequently switched to tenofovir-based therapy (ADV, TDF, or TAF) and have not received entecavir or telbivudine.
干预措施: Viral genetic material from blood samples using advanced sequencing technology (Diagnostic Test)
结局指标
主要结局
Prevalence of entecavir resistance-associated mutations in the HBV polymerase/RT region detected by Oxford Nanopore sequencing.
时间窗: March 15th, 2026-March 15th, 2027
Detection of entecavir resistance-associated mutations (T184, S202, M250), with or without lamivudine resistance background mutations (L180M, M204V/I), in the HBV polymerase/RT region by Oxford Nanopore sequencing of peripheral blood-derived cccDNA. Mutations will be reported if detected at an allele frequency ≥5%.
次要结局
- Comparison of mutations between two groups.(March 15th, 2026-March 15th, 2027)
- Association between HBV-DNA level and resistance-associated mutation presence.(March 15th, 2026-March 15th, 2027)
- Duration of lamivudine exposure and secondary mutations.(March 15th, 2026-March 15th, 2027)
- Classical lamivudine resistance mutations and their co-occurrence with ETV resistance mutations.(March 15th, 2026-March 15th, 2027)
研究者
Yaşar Bayındır, MD
Chief Physican
Guven Health Group