Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Osaka, Japan.
Department of Clinical Research and Genetic Oncology, Osaka International Cancer Institute, Osaka, Japan.
PLoS One. 2024 Oct 24;19(10):e0311930. doi: 10.1371/journal.pone.0311930. eCollection 2024.
Treatment strategies for preventing liver fibrosis have not yet been established. Letrozole, widely used for breast cancer, has recently been reported to suppress liver fibrosis in murine models. Therefore, we aimed to validate the suppressive effects of letrozole on liver fibrosis in the clinical setting. From 2006 to 2020, 23 consecutive patients who received continuous letrozole treatment for 24 months or more and had a liver fibrosis marker FIB-4 index of ≥ 2.30, were included. Forty-three patients who underwent anastrozole treatment for 24 months or more and had a liver fibrosis marker FIB-4 index of ≥ 2.30, were also included as controls. The Fisher exact, chi-square, unpaired Student t, and paired Student t test were used to analyze the data. The patient characteristics were similar between the letrozole- and anastrozole-treated patient groups. Among the letrozole-treated patients, the mean FIB-4 index tended to decline during letrozole treatment; a significant decrease was observed at 18 and 24 months compared with the baseline values (p = 0.044 and p = 0.013). In addition, the mean aspartate aminotransferase-to-platelet ratio index (APRI) decreased during letrozole treatment; the values at 18 and 24 months were significantly lower than those at baseline (p = 0.024 and p = 0.026). In contrast, among anastrozole-treated patients, the mean FIB-4 index and APRI did not change during anastrozole treatment. When changes in the FIB-4 index were further examined in a limited number of patients with a FIB-4 index ≥ 2.67, a significant reduction in the FIB-4 index at 24 months compared with baseline was also observed in letrozole-treated patients (p = 0.023), but not in anastrozole-treated patients. In conclusion, our findings support a possible suppressive effect of letrozole on liver fibrosis in the clinical setting. Further studies are required to better understand the pharmacological effects of letrozole.
治疗肝纤维化的策略尚未确立。来曲唑广泛用于治疗乳腺癌，最近有报道称其可抑制鼠模型的肝纤维化。因此，我们旨在验证来曲唑在临床环境中对肝纤维化的抑制作用。2006 年至 2020 年，连续 23 例接受来曲唑治疗 24 个月或以上且肝纤维化标志物 FIB-4 指数≥2.30 的患者纳入研究。43 例接受阿那曲唑治疗 24 个月或以上且肝纤维化标志物 FIB-4 指数≥2.30 的患者作为对照。采用 Fisher 确切检验、卡方检验、独立样本 t 检验和配对 t 检验分析数据。来曲唑组和阿那曲唑组患者的特征相似。在来曲唑治疗的患者中，FIB-4 指数在来曲唑治疗期间呈下降趋势；与基线值相比，18 个月和 24 个月时显著下降（p=0.044 和 p=0.013）。此外，来曲唑治疗期间天门冬氨酸氨基转移酶-血小板比值指数（APRI）下降；18 个月和 24 个月时的值明显低于基线值（p=0.024 和 p=0.026）。相比之下，在阿那曲唑治疗的患者中，FIB-4 指数和 APRI 在阿那曲唑治疗期间没有变化。当进一步在 FIB-4 指数≥2.67 的有限数量患者中检查 FIB-4 指数的变化时，也观察到来曲唑治疗的患者在 24 个月时与基线相比 FIB-4 指数显著降低（p=0.023），而阿那曲唑治疗的患者则没有。总之，我们的研究结果支持来曲唑在临床环境中对肝纤维化的抑制作用。需要进一步的研究来更好地了解来曲唑的药理作用。
