Case Report: dynamic monocyte reprogramming during ALSS therapy in type B HBV-ACLF revealed by single-cell transcriptomics.

BACKGROUND

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is characterized by intense systemic inflammation and immune dysregulation, with monocytes playing a central role in its progression. Patients with HBV-ACLF typically receive comprehensive treatment including artificial liver support system (ALSS). Here, we report a case of HBV-ACLF in which single-cell RNA sequencing (scRNA-seq) showing dynamic reprogramming of monocyte upon ALSS treatment.

METHODS

We conducted the single-cell and bulk RNA sequencing with peripheral blood mononuclear cells (PBMCs) from a patient with type B HBV-ACLF, both before and after ALSS therapy. The scRNA-seq data were subjected to bioinformatic analyses, including graph-based clustering, pseudotime trajectory inference, and M1/M2 polarization scoring. Findings were further validated using matched bulk transcriptomes.

RESULTS

Among PBMCs, monocytes displayed the most dramatic transcriptomic changes. A distinct inflammatory monocyte subpopulation (Mono4) was identified, featuring upregulated mitochondrial genes, and enrichment of secreted factors associated with platelet activation and systemic inflammation. During the ALSS-based comprehensive treatment course, we observed a decreased proportion of Mono4 and attenuation of its pro-inflammatory secretory signature. Pseudotime analysis further revealed a differentiation trajectory from classical monocytes (Mono1 and Mono2) to Mono4, which decreased with treatment. Consistent with these findings, bulk RNA-seq deconvolution confirmed the monocyte-centric immune landscape.

CONCLUSION

In this case report, comprehensive treatment including ALSS was linked to monocyte reprogramming and the decreased pro-inflammatory Mono4 subpopulation. Furthermore, Mono4 may play a central role in the systemic hyperinflammatory response.