Non-alcoholic fatty liver disease (NAFLD) is increasing globally, and seeking therapeutic molecule targets is urgent. Several studies have demonstrated that IL-33 plays an important role in the progression of Non-alcoholic steatohepatitis (NASH) with fibrosis and the proliferation of hepatocellular carcinoma (HCC). However, whether the inhibition of IL-33 signaling prevents NAFLD from progressing to NASH and HCC has not been clarified. We investigated the effects of a novel antibody, IL-33RAb, and luseogliflozin, a SGLT2 inhibitor, when administered to a model mouse for NASH and HCC, and their effects were compared to investigate the mechanisms of how IL-33 is involved in the pathogenesis of NASH progression. Compared with the positive control of luseogliflozin, inhibition of IL-33 signaling ameliorated decreasing hepatic fibrosis via decreasingαSMA and MCP-1, and also partially suppressed the progression of the HCC cell line in in vitro experiments. These findings suggest that inhibition of IL-33 possibly prevents progression from NASH to HCC, and their effect may be a newly arrived therapeutic agent.

非酒精性脂肪肝病（NAFLD）在全球范围内不断增加，寻找治疗分子靶点刻不容缓。多项研究表明，IL-33 在伴有纤维化的非酒精性脂肪性肝炎 (NASH) 进展和肝细胞癌 (HCC) 增殖中发挥重要作用。然而，抑制IL-33信号传导是否能阻止NAFLD进展为NASH和HCC尚不清楚。我们研究了新型抗体 IL-33RAb 和SGLT2抑制剂 luseogliflozin 给予 NASH 和 HCC 模型小鼠时的效果，并比较了它们的效果，以研究 IL-33 参与发病机制的机制NASH 进展。与 luseogliflozin 的阳性对照相比，IL-33 信号传导的抑制通过减少 αSMA 和 MCP-1 改善了肝纤维化，并且在体外实验中还部分抑制了 HCC 细胞系的进展。这些发现表明，抑制 IL-33 可能会阻止 NASH 进展为 HCC，其作用可能是一种新的治疗药物。