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.
Accuracy, repeatability, reproducibility and reference ranges of primary sclerosing cholangitis specific biomarkers from quantitative MRCP
This study assesses the repeatability and reproducibility of quantitative MRCP-derived metrics on Siemens, GE and Philips scanners at both 1.5T and 3T. All patients were scanned on a Siemens Prisma 3T scanner which acted as the reference scanner, with a subset scanned on the remaining scanners. High accuracy, repeatability and reproducibility were demonstrated for the quantitative MRCP-derived metrics. Measured accuracy had an absolute bias of 0.0-0.1 for strictures and 0.1-0.2 for dilatations across all scanners (95% limits of agreement within ± 1.0). In vivo reference ranges for healthy population and repeatability coefficients for the quantitative MRCP-derived metrics across the scanners were also calculated. Some examples of the reference ranges for the healthy population are number of ducts <38, total number of dilatations <8 and total number of strictures <6. Findings showed sufficient cross-scanner reproducibility to distinguish healthy volunteers from PSC patients and should be well suited for multi-centre trials and assessment of biliary tree health.
High prevalence of MASLD in psoriasis and psoriatic arthritis assessed with multiparametric magnetic resonance imaging
Using LiverMultiScan the prevalence of steatotic liver disease in a prospective cohort of individuals with psoriatic disease from secondary care was 44%, whereas 22% of these individuals had MASH, both higher than in individuals without PsD (fully matched controls and healthy controls). 54% of individuals with psoriatic disease and liver disease detected with LiverMultiScan had normal liver function blood tests. No significant difference in levels of liver disease was observed between those with or without prior exposure to methotrexate. This study underscores the complex interplay between MASLD and psoriatic disease, emphasising the need for early detection with multiparametric MRI.
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.