Assessment of Hepatitis B Virus Intra-host Population and Host-specific Immune Marker Diversity

Study Overview
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Brief Summary
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In this project proposal, the investigators will investigate the genetic alterations of Hepatitis B Virus (HBV) strains circulating in Belgian patients who developed end stage liver disease. Additionally, the investigators will compare and link these data sets with three genetic factors involved in immune system response.

Detailed Description
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This project proposes to identify and characterize the genetic alterations associated with intra-host evolution of HBV from a chronically infection status to an end-stage liver disease status.

Official Title
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Assessment of Hepatitis B Virus Intra-host Population and Host-specific Immune Marker Diversity With Next-generation Sequencing: From Chronic Infection to End-stage Liver Disease and Liver Cancer

Conditions
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Hepatitis B, Hepatitis B, Chronic, End Stage Liver Disease, Carcinoma, Hepatocellular

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Study group: Clinical diagnosis of advanced liver disease related to chronic Hepatitis B infection (cirrhosis, hepatocellular carcinoma,..) Availability of serum samples Control group: Clinical diagnosis of liver disease related to chronic Hepatitis B infection in a pre-advanced stage Matched demographic and geographic characteristics to study group Availability of serum samples Exclusion Criteria: Liver disease caused by other hepato-tropic viruses Patients with auto-immune diseases
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Chronic Hepatitis B<br>Diagnosis of Hepatitis B related liver disease in a pre-advanced stage | |
| End stage liver disease<br>Diagnosis of advanced liver disease related to Hepatitis B | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| genetic variants of Hepatitis B | Virus variants will be identified by amino acid or nucleotide variations (insertions or deletions) in different Open Readind Frames (ORFs) of the HBV genome by using next-generation sequencing. Comparison of virus variants within one patient Comparison of virus variants between patients with end stage liver disease and patients with a chronic Hepatitis B infection. Determination of the viral load by quantitative Polymerase Chain Reaction (PCR). | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| genetic variation in host-specific immune markers | Amplification of HLA-A, HLA-B, HLA-C class I and HLA class II using PCR methods and next-generation sequencing Amplification of KIR genes: 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DS1 and 1D, 2DL1 2DL2, 2DL3, 2DL5 and 3DL1 using PCR methods and next-generation sequencing Amplification of SNPs in TNF alfa, TGF beta1 and IFN-R using PCR methods and next-generation sequencing | at day of enrollment |