Aria Khan, MD1, Shahzaib Maqbool, MBBS2, Shahzad Zafar, MD3, Arslan Kareem, MBBS2 1NYC Health + Hospitals/Woodhull, Jamaica, NY; 2Rawalpindi Medical University, Rawalpindi, Punjab, Pakistan; 3Howard University Hospital, Washington, DC Introduction: Nonalcoholic steatohepatitis (NASH) is a progressive liver disease that can lead to cirrhosis and hepatocellular carcinoma. With no prior FDA-approved oral therapies, Resmetirom—a selective THR-β agonist—has emerged as a promising option. We performed a meta-analysis of randomized controlled trials to evaluate its efficacy and safety in patients with biopsy-proven or presumed NASH. Methods: A systematic literature search identified randomized controlled trials evaluating Resmetirom in adults with NASH. Key outcomes included NASH resolution without fibrosis worsening, ≥1-stage fibrosis improvement without NASH worsening, and liver fat reduction via MRI-PDFF. Lipid profile changes and safety data were also analyzed. Meta-analysis was conducted using the DerSimonian and Laird random-effects model, with statistical analysis performed in Review Manager (RevMan) version 5.4. Heterogeneity was assessed using the I² statistic. Results: Three randomized trials including 1,291 patients (805 Resmetirom, 486 placebo) were analyzed. NASH resolution without fibrosis worsening occurred in 26.7% of Resmetirom-treated patients versus 8.7% in the placebo group (RR = 2.66; 95% CI: 1.98–4.19; p < 0.001; I² = 0%). Fibrosis improvement by ≥1 stage without NASH worsening was seen in 23.1% vs. 13.2%, respectively (RR = 1.87; 95% CI: 1.12–2.78; p < 0.001; I² = 15%). Liver fat reduction on MRI-PDFF was significantly greater with Resmetirom (mean difference −34.6%; 95% CI: −39.2 to −31.8; p < 0.001; I² = 12%). Resmetirom also reduced LDL cholesterol (−13.7% to −21.4%) and triglycerides (−57% to −68% in those with elevated baseline levels). The most common adverse events were mild gastrointestinal symptoms, such as diarrhea and nausea. Discussion: This meta-analysis shows that Resmetirom significantly improves key histological outcomes in NASH, including resolution of inflammation and regression of fibrosis, alongside marked reductions in hepatic steatosis. It also provides cardiometabolic benefits through lipid modulation and is generally well-tolerated, with a safety profile similar to placebo. These results support Resmetirom as a promising oral therapy for NASH. Further studies should evaluate its long-term impact on cirrhosis progression and outcomes.
Disclosures: Aria Khan indicated no relevant financial relationships. Shahzaib Maqbool indicated no relevant financial relationships. Shahzad Zafar indicated no relevant financial relationships. Arslan Kareem indicated no relevant financial relationships.
Aria Khan, MD1, Shahzaib Maqbool, MBBS2, Shahzad Zafar, MD3, Arslan Kareem, MBBS2. P5853 - Targeting THR-β in Nonalcoholic Steatohepatitis (NASH): A Meta-Analysis of Resmetirom’s Efficacy and Safety, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.
