Zou Zhengsheng, Li Baosen, Xu Dongping, Zhang Zheng, Zhao Jing-Min, Zhou Guangde, Sun Yanling, Huang Lei, Fu Junliang, Yang Yongping, Jin Lei, Zhang Wei, Zhao Jun, Sun Ying, Xin Shaojie, Wang Fu-Sheng
Department of Severe Liver Diseases, Beijing 302 Hospital, Beijing Institute of Infectious Diseases, Beijing, China.
J Clin Gastroenterol. 2009 Feb;43(2):182-90. doi: 10.1097/MCG.0b013e3181624464.
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.
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.
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.
Intrahepatic proinflammatory IFN-gamma and TNF-alpha expressions were markedly up-regulated in ACLF compared with CHB and NC. However, similar anti-inflammatory IL-10 expressions were observed in ACLF and CHB. IFN-gamma overexpression correlated significantly with increased CD4 and CD8 T-cell accumulation. TNF-alpha up-regulation also correlated significantly with increased KCs.
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.
本研究旨在确定肝内促炎和抗炎细胞因子及其分泌免疫细胞的表达情况，以评估它们在慢性乙型肝炎病毒（HBV）感染患者的慢加急性肝衰竭（ACLF）发病机制中的作用。
ACLF通常影响已确诊的代偿性慢性肝病患者，这些患者肝功能会急性恶化。在中国，由于慢性HBV感染的高流行率，HBV相关的ACLF患者占ACLF患者的80%以上。临床观察表明，该疾病的恶化可能与宿主免疫反应相关，但相关的潜在机制仍 largely unknown。
采用免疫组织化学方法分析了ACLF患者、慢性乙型肝炎（CHB）患者和正常对照（NC）肝脏中干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）及其分泌的CD4、CD8 T细胞和库普弗细胞（KC）的原位表达。
与CHB和NC相比，ACLF患者肝内促炎IFN-γ和TNF-α表达明显上调。然而，在ACLF和CHB中观察到相似的抗炎IL-10表达。IFN-γ的过表达与CD4和CD8 T细胞积累增加显著相关。TNF-α的上调也与KC增加显著相关。
促炎和抗炎细胞因子的表达失衡以及CD4、CD8 T细胞和KC的积累增加可能导致HBV感染的ACLF的免疫发病机制。
