Rilpivirine Activates STAT1 in Non-Parenchymal Cells to Regulate Liver Injury in People Living with HIV and MASLD

• Published in: Biomedicines Vol. 12; no. 7; p. 1454
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.06.2024
• Subjects: antiretroviral therapy; Apoptosis; Biopsy; Cell activation; Fatty liver; Fibrosis; hepatic stellate cells; Hepatocytes; HIV; Human immunodeficiency virus; Liver cirrhosis; Liver diseases; MASH; Metabolism; Metabolites; Patients; Population; Stat1 protein; Steatosis; Transcription factors; Ultrasonic imaging; Madrid Spain; Spain; hepatic stellate cells; MASH; fibrosis; antiretroviral therapy
• ISSN: 2227-9059; 2227-9059
• 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.