Department of Hepatology, Qilu Hospital of Shandong University, Jinan 250012, China.
Institute of Hepatology, Shandong University, Jinan 250012, China.
Int J Med Sci. 2019 Mar 9;16(3):461-469. doi: 10.7150/ijms.30424. eCollection 2019.
Acute-on-chronic hepatitis B liver failure (ACHBLF) refers to the acute deterioration of liver function during chronic hepatitis B virus infection, and is associated with high mortality, with rapid progression to death. Nucleotide-binding oligomerisation domain-like receptors (NLRs) Family Pyrin Domain Containing 3(NLRP3) inflammasome contributed to the pathogenesis of D-galactosamine and lipopolysaccharide-induced acute liver failure. However, the profile of NLRP3 in patients with ACHBLF has not been demonstrated. This study was therefore conducted to investigate the expression of NLRP3 in patients with ACHBLF and identify the effect of glucocorticoid on NLRP3. We recruited 70 patients with ACHBLF undergoing glucocorticoid treatment for 28 days, 30 patients with chronic hepatitis B (CHB), and 24 healthy controls (HCs) in this study. The relative messenger RNA (mRNA) level of NLRP3 and related genes were measured by reverse transcription polymerase chain reaction, the plasma levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were measured by enzyme-linked immunosorbent assay. The mRNA level of NLRP3 was significantly higher in patients with ACHBLF than in patients with CHB as well as HCs (<0.05). The plasma levels of IL-1β and IL-18 in patients with ACHBLF were significantly higher than in patients with CHB and HCs (<0.05). The relative mRNA level of NLRP3 in surviving patients decreased significantly compared with that in patients who did not survive after glucocorticoid treatment (<0.05). In conclusion, NLRP3 increased in patients with ACHBLF. Glucocorticoid could downregulate the expression of NLRP3 in surviving patients with ACHBLF.
慢加急性乙型肝炎肝衰竭（ACHBLF）是指在慢性乙型肝炎病毒感染过程中出现的肝功能急性恶化，其死亡率高，病情迅速进展至死亡。核苷酸结合寡聚化结构域样受体（NLRs）家族包含pyrin 结构域蛋白 3（NLRP3）炎症小体参与了 D-半乳糖胺和脂多糖诱导的急性肝衰竭的发病机制。然而，ACHBLF 患者中 NLRP3 的特征尚未得到证实。因此，本研究旨在探讨 NLRP3 在 ACHBLF 患者中的表达情况，并确定糖皮质激素对 NLRP3 的影响。本研究共纳入 70 例接受糖皮质激素治疗 28 天的 ACHBLF 患者、30 例慢性乙型肝炎（CHB）患者和 24 例健康对照（HCs）。采用逆转录聚合酶链反应（RT-PCR）法检测 NLRP3 及相关基因的相对信使 RNA（mRNA）水平，酶联免疫吸附试验（ELISA）法检测白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）的血浆水平。ACHBLF 患者的 NLRP3 mRNA 水平明显高于 CHB 患者和 HCs（<0.05）。ACHBLF 患者的 IL-1β和 IL-18 血浆水平明显高于 CHB 患者和 HCs（<0.05）。糖皮质激素治疗后存活患者的 NLRP3 相对 mRNA 水平与未存活患者相比明显降低（<0.05）。结论：ACHBLF 患者的 NLRP3 增加。糖皮质激素可下调 ACHBLF 存活患者 NLRP3 的表达。
