Introduction
NAFLD, hepatic disorder, biliary epithelial cell injury, OCA, autoimmune liver disease, fibrosis, NASH/NAFLD, NASH, PD, PBC, cholestasis, pruritus, primary biliary cholangitis
HEPATIC DISORDER, PBC, BILIARY CIRRHOSIS, PRIMARY BILIARY CHOLANGITIS, AUTOIMMUNE LIVER DISEASE, FIBROSIS, NON-ALCOHOLIC FATTY LIVER DISEASE, CHOLESTASIS, PRIMARY BILIARY CIRRHOSIS, LIVER DISEASE
Non-alcoholic fatty liver disease (NAFLD) is a common hepatic disorder with a prevalence in Western and Asian countries of 20%–30% [Studies have shown that most patients have no previous symptoms or diagnosis [Dietary modification, exercise, and management of comorbidities have guidelines for the management of NASH/NAFLD which were published by the American Association for the Study of Liver Diseases (AASLD) [Pharmacological therapies for NASH treatment are widely investigated such as insulin sensitizers (metformin and pioglitazone), antioxidants (vitamin E and pentoxifylline), cholesterol-lowering drugs (statins and aramchol), farnesoid X receptor (FXR) agonists (obeticholic acid [OCA] and tropifexor), peroxisome proliferator-activated receptors (PPARs; elafibranor and saroglitazar), thyroid hormone receptor (THR; resmetirom), and glucagon-like peptide (GLP)-1 agonist (liraglutide and semaglutide).Pioglitazone and vitamin E are recommended for NASH treatment, although their long-term efficacy and safety should be established [FXR, a nuclear receptor, regulates metabolic pathways, including glucose homeostasis and inflammatory and fibrogenic processes. Activation of FXR expression is inversely correlated with NASH severity of NASH [The original indication for OCA is primary biliary cholangitis (PBC). PBC, also known as primary biliary cirrhosis, is an autoimmune liver disease that can cause biliary epithelial cell injury, cholestasis, fibrosis, and biliary cirrhosis. FXR activation treats PBC by depressing cholesterol 7α-hydroxylase/bile acid transporters, inducing the production of fibroblast growth factor-19 (FGF-19), a negative regulator of bile acid synthesis, and up-regulating organic solute transporters and the bile salt export pump.TQA3526, developed by Chia Tai Tianqing Pharmaceutical Group Co. Ltd. (Nanjing, China), is a novel FXR developed for use in patients with NASH and/or PBC. TQA3526 is a highly selected TGR5/FXR that is predicted to reduce pruritus compared to OCA (TGR5/FXR ratio of 1:193). The half-maximal effective concentration (ECThis Phase I first-in-human study was designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TQA3526 in healthy Chinese volunteers. Furthermore, this study was used to help select the optimal dosages for subsequent phase 1b and phase 2 studies in patients with NASH or PBC.