Browsing by Author "Arrese, M."

Now showing 1 - 4 of 4
  • No Thumbnail Available
    Item
    Aramchol in patients with nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase 2b trial
    (2021) Ratziu, V.; de Guevara, L.; Safadi, R.; Poordad, F.; Fuster, F.; Flores-Figueroa, J.; Arrese, M.; Fracanzani, Anna L.; Ben Bashat, D.; Lackner, K.; Gorfine, T.; Kadosh, S.; Oren, R.; Halperin, M.; Hayardeny, L.; Loomba, R.; Friedman, S.; Sanyal, Arun J.
    Y Nonalcoholic steatohepatitis (NASH), a chronic liver disease without an approved therapy, is associated with lipotoxicity and insulin resistance and is a major cause of cirrhosis and hepatocellular carcinoma. Aramchol, a partial inhibitor of hepatic stearoyl-CoA desaturase (SCD1) improved steatohepatitis and fibrosis in rodents and reduced steatosis in an early clinical trial. ARREST, a 52-week, double-blind, placebo-controlled, phase 2b trial randomized 247 patients with NASH (n = 101, n = 98 and n = 48 in the Aramchol 400 mg, 600 mg and placebo arms, respectively; NCT02279524). The primary end point was a decrease in hepatic triglycerides by magnetic resonance spectroscopy at 52 weeks with a dose of 600 mg of Aramchol. Key secondary end points included liver histology and alanine aminotransferase (ALT). Aramchol 600 mg produced a placebo-corrected decrease in liver triglycerides without meeting the prespecified significance (-3.1, 95% confidence interval (CI) -6.4 to 0.2, P = 0.066), precluding further formal statistical analysis. NASH resolution without worsening fibrosis was achieved in 16.7% (13 out of 78) of Aramchol 600 mg versus 5% (2 out of 40) of the placebo arm (odds ratio (OR) = 4.74, 95% CI = 0.99 to 22.7) and fibrosis improvement by >= 1 stage without worsening NASH in 29.5% versus 17.5% (OR = 1.88, 95% CI = 0.7 to 5.0), respectively. The placebo-corrected decrease in ALT for 600 mg was -29.1 IU l(-1) (95% CI = -41.6 to -16.5). Early termination due to adverse events (AEs) was <5%, and Aramchol 600 and 400 mg were safe, well tolerated and without imbalance in serious or severe AEs between arms. Although the primary end point of a reduction in liver fat did not meet the prespecified significance level with Aramchol 600 mg, the observed safety and changes in liver histology and enzymes provide a rationale for SCD1 modulation as a promising therapy for NASH and fibrosis and are being evaluated in an ongoing phase 3 program.
  • No Thumbnail Available
    Item
    Gastrointestinal neuroendocrine tumor with unresectable liver metastases: An example of multimodal therapeutic approach
    (2015) Martínez, J.; Besa, S.; Arab, J.P.; Quintana, J.C.; Regonesi, C.; Huete, A.; Jarufe, N.; Guerra, J.F.; Benítez, C.; Arrese, M.
  • Thumbnail Image
    Item
    Incidence and prevalence of hepatitis C virus infection in Chile.
    (2005) González, R.; Soza, A.; Hernández, V.; Pérez, R.M.; Alvarez, M.; Morales, A.; Arellano, M.; Riquelme, A.; Viviani, P.; Covarrubias, C.; Arrese, M.; Miquel, J.F.; Nervi, F.
  • No Thumbnail Available
    Item
    Nuclear Receptors, Inflammation, and Liver Disease: Insights for Cholestatic and Fatty Liver Diseases
    (2010) Arrese, M.; Karpen, S. J.
    Members of the nuclear receptor (NR) superfamily of ligand-activated transcription factors are players of substantial relevance in the regulation of hepatic gene expression. NRs direct normal physiology and metabolism, adaptations to liver disease, and responses to inflammation and toxins. They also contribute to the regenerative response. In this review, we summarize currently available experimental and clinical data, focusing on the role of NRs in cholestasis and nonalcoholic fatty liver disease (NAFLD). We also highlight the potential of NRs as targets for safe and effective therapeutic interventions.