Integrated Multi-Omics Analysis of Treatment-Naive Patients With Chronic HBV Infection (HBV-MultiOmics)
Cross-Sectional Integrated Multi-Omics Study of Treatment-Naive Patients With Chronic Hepatitis B Virus Infection
This is a single-center, cross-sectional, observational study involving approximately 1,000 treatment-naive patients with chronic hepatitis B virus (HBV) infection at Beijing Ditan Hospital, Capital Medical University.
The study aims to investigate the relationship between HBV genetic characteristics, host molecular profiles, and clinical features of chronic HBV infection. Clinical and laboratory information, including liver function tests, HBV DNA levels, hepatitis B surface antigen (HBsAg) levels, and liver fibrosis assessments, will be collected from eligible participants.
Existing clinical data and stored serum samples will be used when authorized and approved by the Ethics Committee. Newly enrolled participants will contribute residual serum samples obtained after routine clinical testing. No additional blood collection or experimental treatment will be required for this study.
HBV whole-genome sequencing data will be analyzed to characterize viral genotypes, mutations, and viral diversity. In approximately 300 selected participants, serum metabolomics, quantitative proteomics, and immune-related factors will also be examined.
By integrating viral, metabolic, protein, immune, and clinical data, this study aims to identify molecular features and potential biomarkers associated with liver inflammation, early liver fibrosis, viral replication, and HBsAg expression. The findings may help improve understanding of differences among patients with chronic HBV infection and provide a basis for future research on risk assessment and disease management.
Descripción general del estudio
Estado
Condiciones
Descripción detallada
Study Design This is a single-center, prospective, cross-sectional, observational, and non-interventional study conducted at Beijing Ditan Hospital, Capital Medical University. Approximately 1,000 treatment-naive patients with chronic HBV infection will be included, consisting of approximately 400 eligible existing cases and 600 prospectively enrolled participants.
Study Population Eligible participants will have persistent hepatitis B surface antigen (HBsAg) positivity for more than six months and a diagnosis of chronic HBV infection. Participants must not have received nucleos(t)ide analogues, interferon, or other specified treatments that may significantly affect the study-related indicators before the observation time point.
Patients with other viral hepatitis infections, autoimmune liver disease, alcoholic liver disease, advanced cirrhosis, or hepatocellular carcinoma will be excluded.
Data and Sample Collection Demographic characteristics, clinical history, liver biochemical parameters, liver fibrosis assessment results, and HBV-related virological indicators will be collected from medical records and study databases.
Existing clinical data and stored serum samples will be used only after verification of their original consent and authorization for secondary use, subject to ethics approval. For prospectively enrolled participants, residual serum samples from routine clinical testing will be collected. No additional research-related blood collection will be performed, and routine clinical management will not be altered.
Multi-Omics Analysis HBV whole-genome sequencing data will be used to characterize viral genotypes, subtypes, mutations, and quasispecies diversity. Existing authorized sequencing data will be prioritized, with supplementary sequencing performed when necessary.
Approximately 300 representative participants will be selected according to HBV genotype, HBeAg status, ALT levels, and liver fibrosis status for host multi-omics analyses, including:
- Untargeted serum metabolomics using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).
- Quantitative proteomics using tandem mass tag (TMT)-based technology.
- Multiplex immune factor analysis to measure inflammatory, anti-inflammatory, and chemokine-related molecules.
Statistical Analysis Statistical analyses will be performed using R software. Group comparisons, correlation analyses, multivariable regression, pathway enrichment, and integrated multi-omics analyses will be conducted. Machine learning methods, including LASSO regression and random forest or XGBoost when appropriate, will be explored to identify relevant molecular features and develop models for clinical phenotypes such as elevated ALT and early liver fibrosis.
Study Objectives The primary objective is to investigate associations between HBV genomic characteristics, host multi-omics profiles, and clinical phenotypes. The study also aims to identify potential biomarkers associated with liver inflammation, early fibrosis, viral replication, and HBsAg expression.
This is an observational study. No investigational drugs, medical devices, or therapeutic interventions will be administered. The study is not designed to establish causal relationships or directly evaluate long-term clinical outcomes.
Tipo de estudio
Inscripción (Estimado)
Contactos y Ubicaciones
Ubicaciones de estudio
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Beijing Municipality
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Beijing, Beijing Municipality, Porcelana, 100015
- Beijing Ditan Hospital, Capital Medical University
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Método de muestreo
Población de estudio
The study population consists of approximately 1,000 treatment-naive patients with chronic hepatitis B virus (HBV) infection at Beijing Ditan Hospital, Capital Medical University. The study includes approximately 400 eligible existing cases and 600 prospectively enrolled participants. Participants represent different clinical phases of chronic HBV infection. Approximately 300 representative participants will be selected according to HBV genotype, HBeAg status, ALT levels, and liver fibrosis status for multi-omics analyses. Both male and female participants are eligible. No healthy volunteers will be included.
Descripción
Inclusion Criteria:
- Persistent hepatitis B surface antigen (HBsAg) positivity for more than 6 months.
- Diagnosis of chronic hepatitis B virus (HBV) infection.
- No previous treatment with nucleos(t)ide analogues or interferon before the study observation time point.
- No previous use of immunomodulatory agents or hepatoprotective and anti-inflammatory medications that may significantly affect the study-related indicators before the observation time point.
- Availability of demographic, clinical biochemical, and virological data required for the study.
- Availability of stored serum samples that can be accurately matched with clinical data and meet the quality requirements for subsequent analyses.
- For existing cases, reuse of clinical data and samples must comply with the ethics committee's approval and applicable informed consent requirements. Prospectively enrolled participants must provide written informed consent.
Exclusion Criteria:
- Coinfection with other viral hepatitis infections, including hepatitis A, C, or E.
- Concurrent autoimmune liver disease.
- Alcohol-associated liver disease.
- Advanced liver cirrhosis.
- Hepatocellular carcinoma.
- Incomplete clinical records, virological data, or stored serum samples that do not meet the requirements for the planned analyses.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Modelos observacionales: CASE_ONLY
- Perspectivas temporales: CROSS_SECTIONAL
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Serum ALT Level by HBV Genomic Characteristic Group
Periodo de tiempo: Baseline
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HBV genotypes, subgenotypes, genomic mutations, and quasispecies heterogeneity will be characterized using HBV whole-genome sequencing data. Serum alanine aminotransferase (ALT) levels will be obtained from routine clinical laboratory records and expressed in units per liter (U/L). The association between HBV genomic characteristics and serum ALT levels will be evaluated using appropriate statistical methods. |
Baseline
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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APRI Score by HBV Genomic Characteristic Group
Periodo de tiempo: Baseline
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The Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) will be calculated using serum AST levels and platelet counts obtained from routine clinical laboratory records. APRI is a dimensionless index. HBV genomic characteristics will be determined using HBV whole-genome sequencing data. APRI values will be compared across prespecified HBV genomic characteristic groups. |
Baseline
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FIB-4 Index by HBV Genomic Characteristic Group
Periodo de tiempo: Baseline
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The Fibrosis-4 (FIB-4) index will be calculated using age, serum AST, serum ALT, and platelet count obtained from clinical records. FIB-4 is a dimensionless index. HBV genomic characteristics will be determined using HBV whole-genome sequencing data. FIB-4 values will be compared across prespecified HBV genomic characteristic groups. |
Baseline
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Liver Stiffness Measurement by HBV Genomic Characteristic Group
Periodo de tiempo: Baseline
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Liver stiffness measurement (LSM) will be obtained from available clinical liver elastography records and expressed in kilopascals (kPa). HBV genomic characteristics will be determined using HBV whole-genome sequencing data. LSM values will be compared across prespecified HBV genomic characteristic groups. |
Baseline
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Serum HBV DNA Level by HBV Genomic Characteristic Group
Periodo de tiempo: Baseline
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Serum HBV DNA levels will be obtained from routine clinical virological testing and expressed in international units per milliliter (IU/mL). HBV genomic characteristics, including genotypes, genomic mutations, and quasispecies features, will be determined using HBV whole-genome sequencing data. Serum HBV DNA levels will be compared across prespecified HBV genomic characteristic groups. |
Baseline
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Quantitative HBsAg Level by HBV Genomic Characteristic Group
Periodo de tiempo: Baseline
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Serum quantitative hepatitis B surface antigen (HBsAg) levels will be obtained from routine clinical laboratory records and expressed in international units per milliliter (IU/mL). HBV genomic characteristics will be determined using HBV whole-genome sequencing data. Quantitative HBsAg levels will be compared across prespecified HBV genomic characteristic groups. |
Baseline
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Serum Metabolomic Profiles
Periodo de tiempo: Baseline
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Untargeted serum metabolomic profiling will be performed in approximately 300 selected participants using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Metabolites, including lipids, amino acids, bile acids, carbohydrates, and organic acids, will be profiled. The primary data output will consist of normalized relative metabolite abundance values (arbitrary units). Metabolomic profiles will be compared across prespecified clinical and virological subgroups. |
Baseline
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Serum Quantitative Proteomic Profiles
Periodo de tiempo: Baseline
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Serum quantitative proteomic profiling will be performed in selected participants using tandem mass tag (TMT)-based quantitative proteomics. Protein expression profiles, including inflammation-related proteins and fibrosis-related proteins, will be characterized. Protein abundance will be expressed as normalized relative quantitative values derived from TMT reporter ion intensities (arbitrary units). Differential protein expression across prespecified clinical and virological subgroups will be evaluated. |
Baseline
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Serum Immune-Related Factor Profiles
Periodo de tiempo: Baseline
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Serum immune-related factors will be quantified in selected participants using a multiplex bead-based assay (Luminex technology). The panel includes tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-2 (IL-2), interferon-gamma (IFN-γ), interleukin-10 (IL-10), CXCL8, and IP-10 (CXCL10). Factor concentrations will be determined using standard calibration curves and expressed in picograms per milliliter (pg/mL), subject to assay quantification limits. Differences in immune factor concentrations across prespecified clinical and virological subgroups will be evaluated. |
Baseline
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Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Infecciones transmitidas por la sangre
- Procesos Patológicos
- Enfermedad crónica
- Atributos de la enfermedad
- Infecciones
- Enfermedades virales
- Enfermedades del Sistema Digestivo
- Enfermedades del HIGADO
- Hepatitis, Viral, Humana
- Enfermedades contagiosas
- Infecciones por virus de ADN
- Infecciones por Hepadnaviridae
- Hepatitis Crónica
- Hepatitis
- Condiciones Patológicas, Signos y Síntomas
- Hepatitis B
- Hepatitis B Crónica
Otros números de identificación del estudio
- ZZLX2026048
Plan de datos de participantes individuales (IPD)
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Información sobre medicamentos y dispositivos, documentos del estudio
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