Single-nucleus RNA sequencing reveals HBV-driven metabolic reprogramming and TIMP1-mediated fibrosis in human-liver-chimeric mice

Introduction: Hepatitis B virus (HBV) infection remains a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma worldwide. Despite advances in antiviral therapies, the mechanisms underlying HBV-induced metabolic reprogramming and liver fibrosis remain poorly understood. Methods: We employed single-nucleus RNA sequencing (snRNA-seq) which is particularly suitable for hepatocytic sequencing to dissect the transcriptional landscape of HBV-infected and uninfected hepatocytes in humanized URG mice (Hu-URG). Results and Discussion: phenotype was also observed in liver biopsies from chronic HBV patients, underscoring its clinical relevance. Our findings highlight HBV-driven metabolic adaptation and identify TIMP1 as a potential mediator of fibrosis in uninfected hepatocytes, offering novel insights into HBV pathogenesis and therapeutic targeting.