Imbalanced Intrahepatic Cytokine Expression of Interferon-γ, Tumor Necrosis Factor-α, and Interleukin-10 in Patients With Acute-on-Chronic Liver Failure Associated With Hepatitis B Virus Infection

Goals: This Study attempts to determine expressions of intrahepatic proinflammatory and anti-inflammatory cytokines and their secreting immunocytes to evaluate their roles in the pathogenesis of acute-on-chronic liver failure (ACLF) in chronically hepatitis B virus (HBV)-infected patients. Background: ACLF generally affects patients with established, compensated chronic liver diseases who develop an acute deterioration in liver function. In China, HBV-associated ACLF patients account for more than 80% of ACLF patients owing to a high prevalence of chronic HBV infection. Clinical observation showed that the deterioration of this disease may correlate with host immune responses, but related underlying mechanism remains largely unknown. Study: In situ expressions of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), and their secreting CD4. CD8 T cells, and Kupffer cells (KCs) were analyzed in the livers of patients with ACLF. chronic hepatitis B (CHB), and normal controls (NC) using immunohistochemistry. Results: Intrahepatic proinflammatory IFN-gamma and TNF-alpha expressions were markedly Lip-regulated in ACLF compared with CHB and NC. However, similar anti-inflammatory IL-10 expressions were observed in ACLF and CHB. INF-gamma overexpression correlated significantly with increased CD4 and CD8 T-cell accumulation. TNF-alpha up-regulation also correlated significantly with increased KCs. Conclusions: The imbalanced expression of proinflammatory and anti-inflammatory cytokines and increased accumulation of CD4, CD8 T cells, and KCs may contribute to immunopathogenesis in HBV-infected ACLF.