Resmetirom reduces liver stiffness, portal hypertension risk in MASH cirrhosis patients

Treatment with resmetirom improves liver stiffness, fibrosis biomarkers, and risk scores for clinically significant portal hypertension (CSPH) in patients with metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis at 2 years, according to a study.

In addition, resmetirom demonstrates safety and tolerability in this population, reported lead study author Dr Naim Alkhouri of the Arizona Liver Health in Phoenix, Arizona, US.

“[Resmetirom] demonstrated broad, sustained efficacy across multiple noninvasive parameters at 2 years of treatment,” Alkhouri said in a press release. [https://stockhouse.com/news/press-releases/2025/05/10/madrigal-announces-new-clinical-data-demonstrating-rezdiffra-tm-resmetirom]

“A high, statistically significant percentage of patients with CSPH or probable CSPH at baseline shifted to lower risk categories,” he added.

In this study, 122 patients with Child Pugh A MASH cirrhosis (based on MASH F4 on histology biopsy >66 percent of clinical diagnosis) received resmetirom 80 mg for up to 2 years. They underwent assessment for baseline CSPH (Baveno VII) with FibroScan vibration-controlled transient elastography (VCTE) and platelet count. This was confirmed via magnetic resonance elastography (MRE).

Alkhouri and his team analysed the noninvasive biomarkers and imaging at baseline and at 2 years. They then presented the results as mean change or percent change from baseline.

Improvements

At baseline, the mean age of patients was 61.3 years, and their mean BMI was 35.3 kg/m². Of the participants, more than half (56 percent) were female, nearly one in four (27 percent) were Hispanic, and the majority (65 percent) had type 2 diabetes. [EASL 2025, abstract LBO-002]

Resmetirom administration resulted in significant improvements in VCTE (mean change from baseline, ‒6.1 kPa at year 1 and ‒6.7 kPa at year 2).

The study drug also improved the following at year 2: MRE (0.57 kPa), procollagen-3 N-terminal peptide (P3NP; ‒1.6 ng/ml), Agile3+ (‒0.06), Agile4 (0.09), MRI-PDFF (percent change from baseline, ‒33 percent), ALT (‒25 percent), AST (‒21 percent), GGT (‒45 percent), LDL (‒20 percent), ApoB (22 percent), and triglycerides (‒30 percent).

Of the participants, 46 percent and 52 percent achieved a ≥25-percent reduction in VCTE at year 1 and 2, respectively. On the other hand, 12 percent and 9 percent showed a ≥25-percent increase in VCTE.

Portal hypertension

Sixty-three percent of patients were diagnosed as having probable or definitive CSPH at baseline based on the Baveno criteria. However, 20 percent and 28 percent of these individuals no longer met the criteria for CSPH at years 1 and 2, respectively.

In addition, nearly a third (35 percent) of the participants with confirmed F4 at baseline (liver biopsy F4 or platelets <140/MRE ≥5 with VCTE ≥15) transitioned to F3 at year 2 (VCTE <15 and ≥25-percent decrease from baseline).

Treatment discontinuation occurred in 8 percent of patients. The most common adverse events reported were mild gastrointestinal disorders.

“These findings highlight the potential of resmetirom to demonstrate clinical benefit in MAESTRO-NASH OUTCOMES,” an ongoing trial involving 845 patients with MASH cirrhosis, Alkhouri said.

Resmetirom is a selective thyroid hormone receptor beta agonist approved for the treatment of MASH with moderate to advanced liver fibrosis. MASH cirrhosis with CSPH is associated with major adverse liver outcomes, according to the researchers.