Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a liver disorder characterized by steatosis with underlying metabolic risk factors. The prevalence of MASLD continues to rise, leading to increased patient risk of various complications. Recent research has been focused on new therapeutic strategies to reduce the incidence of MASLD and provide effective treatment plans to prevent further irreversible liver damage. The treatment approach is multifactorial, with a primary focus on weight loss and management of underlying comorbidities through lifestyle modifications, pharmacotherapy, or surgical options. Ongoing research is exploring new pharmacological therapies that could enhance the treatment of MASLD.

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.

The rise in liver disease incidence and prevalence has led to increasing morbidity and mortality worldwide. Persistent hepatic inflammation drives disease progression by increasing fibrosis, advancing to cirrhosis, and potentially developing into hepatocellular carcinoma (HCC). Addressing these complications is essential to reduce liver-related mortality. Recent studies suggest that non-steroidal anti-inflammatory drugs, particularly aspirin, may play a beneficial role in managing liver disease. Aspirin’s anti-inflammatory and chemoprotective effects contribute to slowing disease progression and reducing the risks associated with chronic liver disease (CLD). This review highlights the current literature on the effects of aspirin in CLD, with a focus on patients with metabolic-associated steatotic liver disease (MASLD) and hepatitis B and C. We will examine aspirin’s potential ability to mitigate fibrosis, reduce the incidence of HCC, and lower liver-related mortality. Additionally, we will discuss its potential side effects and safety considerations, particularly in the context of liver disease, where there is an increased risk of bleeding.

Background.: Liver transplant recipients face high risks of cardiometabolic events after transplant, driven by posttransplant weight gain, diabetes, hypertension, as well as immunosuppression-related side effects. Glucagon-like peptide-1 receptor agonists (GLP1RAs) improve metabolic and cardiorenal outcomes in nontransplant populations, but their role in liver transplant recipients remains understudied. Methods.: This retrospective cohort study used TriNetX data (January 2010–December 2023) to compare outcomes in liver transplant recipients prescribed GLP1RAs (semaglutide, dulaglutide, liraglutide) within 1-mo posttransplant (n = 546) versus nonusers (n = 37 153). Propensity score matching (1:1) balanced demographics, comorbidities, and medications (n = 541 per group). Outcomes included mortality, hospitalizations, cardiovascular/renal/respiratory events, and graft outcomes. Results.: Over a mean follow-up 838.5 d (SD 291.9) in the GLP1RA cohort and 884.3 d (SD 313.7) in the non-GLP1RA group, GLP1RA use was associated with a 43% lower all-cause mortality (7.0% versus 12.9%; hazard ratio [HR], 0.566; 95% confidence interval [CI], 0.381-0.841) and 39% fewer hospitalizations (60.4% versus 74.5%; HR, 0.613; 95% CI, 0.530-0.710). Acute heart failure (HR, 0.386; 95% CI, 0.285-0.524), renal failure/dialysis (HR, 0.489; 95% CI, 0.413-0.579), and respiratory failure (HR, 0.484; 95% CI, 354-0.662) risks were significantly reduced. No differences were observed in graft failure/rejection, myocardial infarction, stroke, atrial fibrillation/flutter, ventricular tachycardia, or ischemic optic neuropathy. Conclusions.: Early GLP1RA initiation in liver transplant recipients was associated with reduced mortality, hospitalizations, respiratory, and cardiorenal complications without compromising graft safety. These findings support GLP1RAs as a promising adjunct therapy, warranting prospective trials to confirm benefits in this high-risk population.

Background: Given aspirin’s biologic plausibility for antifibrotic and antineoplastic effects, we conducted a systematic review and meta-analysis to examine the association between aspirin use and major liver-related outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD). To our knowledge, this is the first systematic review and meta-analysis restricted exclusively to patients with biopsy- or registry-confirmed MASLD. Methods: A comprehensive search of Ovid MEDLINE, Ovid EMBASE, Scopus, and Web of Science was performed in October 2025. Studies enrolling adults with a confirmed MASLD diagnosis were included; those with viral hepatitis or alcohol-related liver disease were excluded. Outcomes assessed included hepatocellular carcinoma (HCC), fibrosis progression, cirrhosis, all-cause and liver-related mortality, gastrointestinal (GI) bleeding, hemorrhagic stroke, and liver disease progression. Hazard ratios (HRs) with 95% CIs were pooled using random-effects models. Heterogeneity was assessed using I² statistics. Results: Seven studies met the eligibility criteria, with approximately 720,000 individuals included. Pooled analysis showed that aspirin use was associated with a significantly lower HCC risk (HR 0.59; 95% CI 0.43–0.81; I² = 83%). No statistically significant association was found between aspirin use and cirrhosis incidence (HR 0.55; 95% CI 0.13–2.37; I² = 83.4%) or GI bleeding (HR 1.11; 95% CI 0.74–1.66; I² = 98.9%). Among the two studies that explored all-cause mortality, aspirin was associated with a modest but statistically significant reduction in all-cause mortality (HR 0.86; 95% CI 0.78–0.95; I² = 0%). Conclusions: Aspirin use is associated with a reduced risk of HCC and all-cause mortality in MASLD without significantly increasing GI bleeding or hemorrhagic strokes. These associations may reflect aspirin’s anti-inflammatory properties in liver disease. Further RCTs are needed to verify the causal role of aspirin in MASLD management.