Case report: Single-cell RNA sequencing of PBMCs highlights monocyte gene expression alterations in a type A HBV-ACLF patient.

Hepatitis B Virus-related acute-on-chronic liver failure (HBV-ACLF) is a severe complication with high fatality rates. However, the underlying mechanisms are still elusive and require further investigation. In this report, we described a case of type A HBV-ACLF in which significant changes were found in monocyte gene expression through single-cell RNA sequencing (scRNA-seq). Furthermore, we observed a shifted M1/M2 polarization as well as dynamic changes in HBV-ACLF markers expression within the circulating monocyte population. The co-expression of HBV-ACLF markers (MERTK, THBS1, PPARγ, and SEMA6B) in the circulating monocyte population suggests that monocytes could play an essential role in the development of HBV-ACLF. By analyzing a public HBV-ACLF cohort with bulk RNA-seq data (64 patients), we showed that the expression level of monocytes marker CD163 gradually increased among normal control individuals (NC, n = 15), patients with liver cirrhosis (LC, n = 10), patients with chronic hepatitis B infection (CHB, n = 10), patients with acute-on-chronic hepatic dysfunction (ACHD, n = 10), and patients with HBV-ACLF (n = 20). Furthermore, the representative HBV-ACLF marker THBS1 was significantly correlated with CD163 in this large clinical cohort. It indicated that the dramatic alteration in monocytes may not be limited to our type A HBV-ACLF patient alone but rather a common phenomenon in HBV-ACLF patients. Collectively, our scRNA-seq analysis showed that the pro-inflammatory status of monocytes had shifted into an anti-inflammatory status in this patient, indicating successful treatment and benign prognosis. Although scRNA-seq is still a time-consuming procedure and difficult to apply in daily clinical practice, this report preliminarily shows the promising potential utility of scRNA-seq in HBV-ACLF patients, by which altered status of monocytes could be unbiasedly detected.