Characteristics of systemic inflammation in hepatitis B-precipitated ACLF: Differentiate it from No-ACLF

Background & Aims: Patients with severe exacerbation of chronic hepatitis B (SE-CHB) are at risk of developing acute-on-chronic liver failure (ACLF). Systemic inflammation (SI) is a major driver of ACLF. The aim of this study was to identify characteristics of SI in hepatitis B-precipitated-ACLF (HB-ACLF), which may be distinct from No-ACLF patients with SE-CHB. Methods: Two cohorts of patients with SE-CHB were enrolled in two tertiary hospitals. The associations between circulating leucocyte counts/subsets and ACLF progression and prognoses were analysed in Cohort A. Cytokine measurements, leucocyte phenotyping and whole blood transcriptomic analyses were performed using peripheral blood samples obtained from patients in Cohort B. Results: Circulating leucocyte counts were higher in the HB-ACLF patients than in the No-ACLF patients (P < .001). Peripheral neutrophilic leucocytosis and monocytosis were associated with lymphopenia. The neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) were correlated with risk of death in patients with SE-CHB. NLR independently predicted progression to ACLF in patients without ACLF at enrolment and short-term mortality in ACLF patients. Plasma IL-6, IL-10, G-CSF and GM-CSF levels were higher in ACLF patients (P < .05). Blood transcriptome analyses showed that genes associated with cell migration and mobility and responses to wounding and bacteria were expressed at higher levels while genes involved in lymphocyte-mediated immunity were expressed at lower levels in HB-ACLF patients than in No-ACLF patients. Conclusions: Systemic inflammation in HB-ACLF was characterized by an excessive innate immune response, which was associated with disease progression and mortality.