Hepatitis B, Chronic
Conditions
Keywords
Chronic hepatitis B, Lamivudine, Entecavir, Antiviral resistance
Brief summary
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.
Detailed description
Hypothesis 1. Entecavir resistance-associated mutations are detectable in both naïve and lamivudine-experienced patients. 2. Prevalence is higher in lamivudine-experienced patients compared to treatment-naïve patients. 3. Longer lamivudine exposure and higher HBV-DNA are associated with resistance. 4. 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. Clinical Significance Chronic hepatitis B management relies on long-term antiviral therapy, and resistance-associated mutations significantly influence treatment success and future therapeutic strategies. Although entecavir has a high genetic barrier, prior lamivudine exposure may predispose patients to secondary resistance mutations, potentially compromising antiviral efficacy. However, the prevalence and distribution of such mutations in the Turkish HBV population remain insufficiently characterized This study will provide: * National-level data on entecavir resistance-associated mutations * Comparative analysis between treatment-naïve and lamivudine-experienced patients * Insight into the clinical relevance of minor resistance variants detected by long-read sequencing Peripheral blood-derived cccDNA sequencing may represent a minimally invasive resistance monitoring tool. The findings may contribute to optimizing antiviral selection strategies, guiding individualized treatment decisions, and informing national hepatitis B management policies. This study will provide national-level data on entecavir resistance mutations in Turkey. It may support individualized antiviral selection and contribute to national HBV management strategies.
Interventions
DIAGNOSTIC_TESTViral genetic material from blood samples using advanced sequencing technology
No intervention
Sponsors
Yaşar Bayındır, MD
SOUTHEAST NEUROLOGY AND INFECTIOUS DISEASES SOCIETY
Study design
Observational model
OTHER
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of entecavir resistance-associated mutations in the HBV polymerase/RT region detected by Oxford Nanopore sequencing. | 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%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of mutations between two groups. | March 15th, 2026-March 15th, 2027 | Comparison of mutation frequency between treatment-naïve and lamivudine-experienced patients. Comparison of mutation frequency between treatment-naïve and lamivudine-experienced patients. Comparison of mutation frequency between treatment-naïve and lamivudine-experienced patients. |
| Association between HBV-DNA level and resistance-associated mutation presence. | March 15th, 2026-March 15th, 2027 | Association between HBV-DNA level and resistance-associated mutation presence in all groups. |
| Duration of lamivudine exposure and secondary mutations. | March 15th, 2026-March 15th, 2027 | Association between duration of lamivudine exposure and secondary mutations. |
| Classical lamivudine resistance mutations and their co-occurrence with ETV resistance mutations. | March 15th, 2026-March 15th, 2027 | Detection of classical lamivudine resistance mutations (M204V/I, L180M) and their co-occurrence with ETV resistance mutations. |
Countries
Turkey (Türkiye)
Outcome results
None listed