Moragrega Ángela B, Busca Carmen, Apostolova Nadezda, Olveira Antonio, Martín-Carbonero Luz, Valencia Eulalia, Moreno Victoria, Bernardino José I, Abadía Marta, González-García Juan, Esplugues Juan V, Montes María L, Blas-García Ana
Departamento de Farmacología, Universitat de València, Av. Blasco Ibáñez, 15, 46010 Valencia, Spain.
FISABIO (Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana), Av. de Catalunya, 21, 46020 Valencia, Spain.
Biomedicines. 2024 Jun 29;12(7):1454. doi: 10.3390/biomedicines12071454.
Liver fibrosis is a key determinant of the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Its increasing prevalence and a lack of effective treatments make it a major health problem worldwide, particularly in people living with HIV, among whom the prevalence of advanced fibrosis is higher. We have published preclinical data showing that Rilpivirine (RPV), a widely used anti-HIV drug, selectively triggers hepatic stellate cell (HSC) inactivation and apoptosis through signal transducer and activator of transcription (STAT)1-mediated pathways, effects that clearly attenuate liver fibrosis and promote regeneration. We performed a retrospective, cross-sectional study of RPV-induced effects on steatosis, inflammation, and fibrosis in liver biopsies from well-controlled HIV-infected subjects diagnosed with MASLD. Patients on RPV exhibited similar levels of HIV-related parameters to those not receiving this drug, while showing a tendency toward improved liver function and lipid profile, as well as an enhanced activation of STAT1 in hepatic non-parenchymal cells in those with identified liver injury. This protective effect, promoting STAT1-dependent HSC inactivation, was observed at different stages of MASLD. Our results suggest that RPV-based therapy is especially indicated in HIV-infected patients with MASLD-derived liver injury and highlight the potential of RPV as a new therapeutic strategy for liver diseases.
肝纤维化是代谢功能障碍相关脂肪性肝病（MASLD）进展的关键决定因素。其患病率不断上升且缺乏有效治疗方法，使其成为全球主要的健康问题，尤其是在HIV感染者中，晚期纤维化的患病率更高。我们已发表临床前数据表明，广泛使用的抗HIV药物利匹韦林（RPV）通过信号转导和转录激活因子（STAT）1介导的途径选择性地触发肝星状细胞（HSC）失活和凋亡，这些作用明显减轻肝纤维化并促进再生。我们对确诊为MASLD的病情得到良好控制的HIV感染受试者的肝活检组织中RPV对脂肪变性、炎症和纤维化的影响进行了一项回顾性横断面研究。接受RPV治疗的患者与未接受该药物治疗的患者表现出相似水平的HIV相关参数，同时肝功能和血脂谱有改善的趋势，并且在已确定肝损伤的患者中，肝非实质细胞中STAT1的激活增强。在MASLD的不同阶段均观察到这种促进STAT1依赖性HSC失活的保护作用。我们的结果表明，基于RPV的治疗尤其适用于患有MASLD所致肝损伤的HIV感染患者，并突出了RPV作为肝病新治疗策略的潜力。
