Publications (New)
TERN-501 monotherapy and combination therapy with TERN-101 in metabolic dysfunction-associated steatohepatitis: the randomized phase 2a DUET trial
This study evaluated the efficacy of the THR-beta agonist TERN-501 as a monotherapy or in combination with TERN- 101 (farnesoid X receptor agonist) in patients with presumed MASH. With 162 patients randomized, the primary endpoint of relative changes in liver fat content at week 12 with TERN-501 monotherapy versus placebo, using MRIPDFF, showed least squares mean (s.e.) of: −15.4% (5.2%) with 1 mg (ns), −27.5% (5.7%) with 3 mg (P = 0.0036) and −44.8% (5.9%) with 6 mg (P<0.0001), versus −4.0% (5.4%) with placebo. cT1 decreased significantly from baseline in the TERN-501 6-mg monotherapy group at week 12 (LS mean (s.e.) change: −72.0 (16.1) ms) versus placebo (3.6 (14.9) ms; P = 0.0008), a significance already seen at week 6. Furthermore, at week 12, significantly more patients who received TERN-501 6 mg achieved a response of ≥80ms reduction in cT1 from baseline compared to placebo (31.8% versus 8.3%, P = 0.0449). Transient elastography (TE) and FibroScan-AST (FAST) score decreased non-significantly in all TERN-501 monotherapy and combination therapy groups. TERN-501 was well tolerated with incidence of adverse events similar to placebo, showing promise as a treatment for MASLD.
Left atrial volume quantification by transthoracic echocardiography versus cardiovascular magnetic resonance imaging: a systematic review and meta-analysis
CMR demonstrates superior technical performance over echocardiography for diagnosing left atrial enlargement, with significantly lower measurement failure rates and more precise volumetric assessment. This meta-analysis of paired studies reveals that echocardiography misdiagnoses left atrial enlargement in 38% of cases, a critical concern given that LA enlargement serves as an important marker of cardiac dysfunction and contributes to pathophysiology in obesity and heart failure with preserved ejection fraction. The documented limitations of echocardiography should be carefully considered when designing clinical pathways for HFpEF and developing interventional clinical trials to ensure optimal diagnostic accuracy and patient outcomes.
Genetic risk amplifies lifestyle effects on hepatic steatosis and its progression: Insights from a population-based cohort.
This study examined the interaction between genetic risk and lifestyle factors on hepatic steatosis and its progression in a large UK Biobank cohort. Results showed that healthy lifestyle behaviours, such as physical activity, diet, reduced sedentary behaviour, and social connections, significantly reduced liver fat content (LFC), especially in individuals with higher genetic risk (PNPLA3 rs738409, TM6SF2 rs58542926, and polygenic risk scores). Lifestyle effects were up to 7-fold stronger in high-risk genetic groups compared to low-risk groups. Additionally, genetic and lifestyle interactions influenced liver inflammation (cT1) and cardiovascular events, highlighting the potential for targeted lifestyle interventions in genetically susceptible populations. Participants with hepatic steatosis also showed a higher prevalence of diabetes, hypertension, and elevated cT1 levels (742ms; p<0.001).
A fasting-mimicking diet programme reduces liver fat and liver inflammation/fibrosis measured by magnetic resonance imaging in patients with type 2 diabetes.
The FIT trial assessed the impact of a fasting-mimicking diet (FMD) on liver health in type 2 diabetes. In 89 participants, monthly 5-day FMD cycles for 12 months significantly reduced cT1 (-29.9 ms, p < 0.01), indicating lower liver inflammation/fibrosis, and PDFF (-2.8%, p < 0.01), reflecting reduced liver fat. Improvements in cT1 and PDFF correlated with reductions in HbA1c, fasting glucose, triglycerides, weight, and total cholesterol, suggesting FMD as a beneficial adjunct to diabetes care.
Severe Dietary Energy Restriction for Compensated Cirrhosis Due to Metabolic Dysfunction-Associated Steatotic Liver Disease: A Randomised Controlled Trial
In this small RCT of adults with obesity diagnosed with compensated cirrhosis due to metabolic dysfunction-associated steatotic liver disease (CC-MASLD), low energy total diet replacement over 12 weeks resulted in weight loss and significant reduction in c T1 (−149.9 ms [95% CI −258.1, −41.7, p = 0.01]), compared to standard of care. In contrast to the observed improvement in cT1, neither liver biochemistry markers (alanine transaminase, aspartate transaminase, and total bilirubin) not liver stiffness changed.
Cardiac and liver impairment on multi-organ MRI and risk of major adverse cardiovascular and liver events
Cardiovascular disease and metabolic dysfunction-associated steatotic liver disease (MASLD) are common conditions associated with high mortality and morbidity, yet opportunities for integrated prevention are under-investigated. We explored the association between impairment in the liver (defined by increased iron-corrected T1 (cT1) time) and/ or heart (reduced left ventricular ejection fraction, LVEF ≤50) and risk of experiencing cardiovascular- or liver-related events or all-cause mortality among 28,841 UK Biobank participants who underwent magnetic resonance imaging (MRI). Cardiac and liver impairment are independently, or in combination, associated with cardiovascular or liver events, suggesting a dual role for MRI in integrated prevention pathways.
Phase 3 trial of semaglutide in metabolic dysfunction–associated steatohepatitis. New England Journal of Medicine.
This paper is an interim analysis of an ongoing phase 3 trial of weekly semaglutide treatment for 72 weeks in people with MASH with significant fibrosis. Results reported show a significant improved liver histology in patients with MASH and stage 2 or 3 fibrosis. Resolution of steatohepatitis without worsening fibrosis occurred in 62.9% of semaglutidetreated patients vs. 34.3% with placebo (difference: 28.7 percentage points; 95% CI, 21.1–36.2; P<0.001). Importantly, in contrast to the phase 2 results, they also observed a modest but significant affect of improvement fibrosis with treatment compared to placebo (14.4 percentage points; 95% CI, 7.5 to 21.3; P<0.001). As expected, semaglutide resulted in significantly greater weight loss compared to the placebo, with a mean reduction of 10.5% vs. 2.0% (P<0.001). Noninvasive markers also showed marked improvement with semaglutide where 55.8% had a ≥0.5-point reduction in ELF score vs. 25.5% with the placebo; 52.0% had ≥30% reduction in liver stiffness (VCTE) vs. 30.3%. PRO-C3 and FAST scores also declined significantly after 72 weeks, aligning with histologic improvements. The high response rates in the placebo group in histology and in crude ultrasound-based NITs highlight the need to more precise noninvasive tests for monitoring treatment response.
Multiparametric magnetic resonance imaging may improve detection of patients with at-risk MASH: Real world experience in hepatology clinics
This real-world study demonstrates the value of iron-corrected T1 (cT1) mapping in identifying at-risk MASLD patients. Among patients with low FIB-4 (<1.3 if ≤65 years of age; <2 if >65 years of age, 58.2% had elevated cT1 (≥800 ms), suggesting increased MASH risk. Elevated cT1 was more common in women (63.6% vs. 36.4%, p<0.01) and those with diabetes (30.3% vs. 5.3%, p=0.03). Results also show that among 79 patients with low FIB-4, 58.2% had elevated cT1, 46.4% had high MRE, and 42.9% (of 49 with available data) had high VCTE. These findings highlight that a substantial proportion of low FIB-4 patients exhibit imaging biomarkers above clinical thresholds, particularly cT1.
Quantitative MRCP metrics as imaging biomarkers to differentiate benign from malignant bile duct obstructions
This retrospective study in 38 patients with biopsy diagnosed malignant (n=23) or benign (n=15) biliary obstructions evaluates whether MRCP+ could be used to differentiate cholangiocarcinoma (CCA) associated malignant obstructions from benign. All bile duct metrics calculated using MRCP+ were found to be significantly higher in malignant biliary obstruction (p<0.05). Total biliary tree volume was found to be the most clinically meaningful predictor of malignant obstructions, with a volume of ≥25ml differentiating between the two populations. As current pathways require either contrast administration or ERCP, quantitative MRCP may be an objective, non-invasive tool to identify CCA.