Transcriptome Classification Reveals Molecular Subgroups in Patients with Hepatitis B Virus.

Area of Science:

• Hepatology and Virology
• Molecular Biology
• Immunology

Background:

• Hepatitis B virus (HBV) infects hepatocytes, causing liver fibrosis and increasing liver cancer risk.
• Host genetics, virology, and immunology influence HBV infection, but mechanisms remain unclear.
• Understanding HBV infection mechanisms is crucial for managing chronic hepatitis B (CHB).

Purpose of the Study:

• To identify molecular subgroups of HBV patients using gene expression data.
• To compare clinical and molecular characteristics among identified subgroups.
• To elucidate the underlying mechanisms of HBV infection in CHB patients.

Main Methods:

• Analysis of gene expression data from 124 HBV patients (GEO accession: GSE84044).
• Identification of molecular subgroups (C1, C2, C3) based on gene expression.
• Comparison of age, fibrosis, inflammation, liver index, and immune cell profiles across subgroups.
• Enrichment analysis of metabolic and inflammatory pathways.

Main Results:

• Three molecular subgroups (C1, C2, C3) were identified in HBV patients.
• The C2 group was youngest; the C3 group showed highest fibrosis and inflammation.
• Metabolism pathways were enriched in C1/C2; inflammation and cancer pathways in C1/C3.
• The C2 group had the highest liver index; C3 had the lowest.
• Distinct immune cell profiles were observed: M1 macrophages in C3, M2 macrophages and neutrophils in C2.

Conclusions:

• Molecular subgrouping provides a novel framework for understanding HBV infection heterogeneity.
• Distinct subgroups exhibit varying degrees of liver damage and immune responses.
• These findings contribute to understanding HBV pathogenesis and may inform future therapeutic strategies for CHB.