Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), are among the most prevalent causes of chronic liver disease worldwide, closely linked to the global rise in overweight and obesity, type 2 diabetes, and metabolic syndrome. Until recently, treatment options were limited to lifestyle interventions, with no approved pharmacologic therapies. Resmetirom, a liver-directed, selective thyroid hormone receptor beta (THR-β) agonist, is a promising disease-modifying agent that targets hepatic lipid metabolism, inflammation, and fibrosis. Clinical trials, including the pivotal phase 3 MAESTRO-NASH and MAESTRO-NAFLD-1 trials, have demonstrated significant improvements in liver fat reduction, lipid profiles, histological endpoints, and health-related quality of life, with a favorable safety profile. In March 2024, the FDA granted accelerated approval of resmetirom for adults with MASH and moderate-to-advanced fibrosis, marking a significant milestone in MASLD treatment. This review discusses the mechanistic rationale, preclinical data, and pivotal clinical trial outcomes supporting resmetirom’s role in MASLD/MASH management, while outlining ongoing research needs, including long-term safety, pediatric evaluation, and biomarker development for optimized patient selection.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease marked by cholestasis and progressive fibrosis. While ursodeoxycholic acid (UDCA) remains the first-line therapy, approximately 30–40% of patients have an inadequate biochemical response, increasing the risk of disease progression. Obeticholic acid (OCA), a potent farnesoid X receptor (FXR) agonist, was the first second-line agent approved by the only Food and Drug Administration (FDA) and has demonstrated moderate biochemical efficacy but limited tolerability due to dose-dependent pruritus and safety concerns in cirrhosis. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, showed substantial alkaline phosphatase (ALP) reductions when added to UDCA, although its long-term benefit remains unconfirmed in large-scale trials and its use remains off-label in the United States, unlike FDA-approved agents. Seladelpar, a selective peroxisome proliferator-activated receptor delta (PPAR-δ) agonist, and elafibranor, a dual PPAR-α/δ agonist, have both recently received FDA accelerated approval after demonstrating significant improvements in ALP, biochemical response rates, and pruritus relief in phase 3 trials. This review summarizes these second-line therapies’ mechanisms, efficacy, safety, and limitations emphasizing the need for individualized treatment decisions and ongoing research into long-term clinical outcomes.

Aortic stenosis is a progressive condition with substantial implications for morbidity and mortality. In recent years, attention has shifted toward risk stratification and the development of individualized management plans to optimize treatment outcomes. The management of asymptomatic patients has become a topic of significant controversy, as emerging studies challenge traditional watchful waiting guidelines and propose the potential benefits of early intervention. While early intervention may reduce overall morbidity and mortality in this patient population, the associated procedural risks remain a critical consideration. This review seeks to analyze the existing literature, offering an updated perspective on patient risk stratification and evidence evaluating both management approaches.