Pan-PPAR agonist lanifibranor improves portal hypertension and hepatic fibrosis in experimental advanced chronic liver disease

• DOI: 10.1016/j.jhep.2020.11.045
• Publication Date: 2020-12-02T16:34:42Z
• Authors: Zoe Boyer-Diaz; Peio Aristu-Zabalza; María Andrés-Rozas; Claude Robert; Martí Ortega-Ribera; Anabel Fernández-...; Pierre Broqua; Jean-Louis Junien; Guillaume Wettstein; Jaime Bosch; Jordi Gracia-Sancho
• Keywords: Chronic liver disease; Hepatic fibrosis; Liver disease

In advanced chronic liver disease (ACLD), deregulated hepatic necroinflammatory processes play a key role in the development of microvascular dysfunction, fibrogenesis, and increased vascular tone, resulting progression ACLD portal hypertension. Given current lack an effective treatment, we aimed to characterise effects pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist lanifibranor 2 preclinical models ACLD, as well cells from patients with ACLD.Cirrhotic rats (thioacetamide or common bile duct ligation; TAA cBDL) randomly received (100 mg/kg/day, po) vehicle for 14 days (n = 12/group). PPAR expression, systemic haemodynamics, presence ascites, sinusoidal endothelial cell (LSEC) phenotype, stellate (HSC) activation, serum transaminases albumin, macrophage infiltration, cytokine fibrosis were determined. Hepatic isolated livers cirrhosis their phenotype was evaluated after treatment either vehicle.TAA-cirrhotic receiving showed significantly lower pressure compared vehicle-treated animals (-15%; p 0.003) without decreasing blood flow, indicating improved resistance. Moreover, lanifibranor-treated TAA-rats decreased LSEC HSC phenotypes, ameliorated function, reduced inflammation, significant regression (-32%; 0.020). These findings confirmed cBDL rat model human cirrhosis, which exhibited phenotypic improvement upon lanifibranor.Lanifibranor ameliorates hypertension decompensated cirrhosis. Promising results further support its clinical evaluation ACLD.Advanced (ACLD) constitutes serious public health issue safe treatments are lacking. This study shows that improves fibrosis, elements pathophysiology disease. Evaluation supports beneficial effects.