Bedford Hospital is a 400-bed district general hospital located in the English town of Bedford, serving north and mid Bedfordshire run by Bedfordshire Hospitals NHS Foundation Trust.
Metabolic dysfunction-associated steatohepatitis (MASH), a potentially progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), increases risk of fibrosis progression, cirrhosis, and liver-related and cardiometabolic morbidity. The first licensed pharmacotherapies, resmetirom and semaglutide, mark a shift in management but practical guidance for real-world implementation is lacking. The British Association for the Study of the Liver and British Society of Gastroenterology MASLD special interest group developed consensus recommendations on patient selection, lifestyle management, and follow-up for MASLD-MASH-specific pharmacotherapy. 37 participants participated in a Delphi process where draft statements developed in working groups were anonymously rated, discussed, and refined. Consensus (≥80% agreement) was reached for 49 statements. The group agreed on the following general recommendation. Two-step non-invasive tests, including the Fibrosis-4 index and vibration-controlled transient elastography, are recommended to identify patients with presumed stage F2-F3 fibrosis (ie, at-risk MASH). Individuals with liver stiffness more than 10 kPa but without evidence of cirrhosis should be considered eligible for treatment. Lifestyle behaviour change intervention should accompany pharmacological treatment, delivered by suitably trained practitioners without delaying access to medication. Treatment discontinuation is advised with evidence of disease progression, cirrhosis development, or drug-induced liver injury. These recommendations offer pragmatic guidance to clinicians and consensus clinical opinion to regulatory bodies to support equitable and effective use of new MASLD-MASH therapies.
Background The phosphocreatine-to-ATP ratio (PCr/ATP), measurable by 31P magnetic resonance spectroscopic imaging (31P-MRSI), is a sensitive marker of myocardial energetic reserve. Regional energetic-mechanical coupling, evaluable only per-segment to avoid confounding from spatially heterogeneous disease, represents an important target for cardiac metabolic trials. We extend our previously validated 7T regional 31P-MRSI approach to patients with cardiovascular disease. Methods Twenty-one participants underwent same-day 7T 31P-MRSI and 3T CMR: 9 healthy volunteers, 4 with type 2 diabetes, 5 with heart failure, and 3 with ischaemic cardiomyopathy. PCr/ATP was mapped across six mid-ventricular AHA segments. Ejection fraction, global longitudinal strain, peak filling rate, and regional circumferential and radial strain were derived from 3T CMR. Group differences were assessed by Kruskal-Wallis test with Bonferroni-corrected pairwise comparisons; segment-level associations by per-segment Spearman correlation and linear mixed effects models. Results PCr/ATP differed significantly across groups (p = 0.005, eta^2 = 0.58), ranging from 1.78 +/- 0.21 in healthy volunteers to 1.10 +/- 0.28 in heart failure. Mean PCr/ATP correlated with ejection fraction (rs = 0.65, p = 0.002), global longitudinal strain (rs = -0.63, p < 0.001), and peak filling rate (rs = 0.52, p = 0.023). Segment-level energetic-mechanical coupling was significant in the anteroseptal and inferoseptal segments (circumferential strain rs = -0.49 to -0.56; radial strain rs = 0.43 to 0.57, all p < 0.05), with no significant associations in other segments, consistent with a displacement-related measurement quality gradient. In ischaemic patients, PCr/ATP was significantly lower in infarct segments (0.79 +/- 0.20) than remote myocardium (1.33 +/- 0.22, p = 0.008, r = 0.62). All three ischaemic patients demonstrated remote PCr/ATP below the healthy volunteer median, with two below the 5th percentile (rank-sum p = 0.018; Fisher p = 0.045). Conclusions Regional 7T 31P-MRSI detects segment-level energetic differences across cardiovascular disease states and reveals spatially specific energetic-mechanical coupling confined to the septal segments in the current ungated acquisition. Energetic impairment in ischaemic cardiomyopathy extends into structurally preserved remote myocardium. These findings support larger studies using regional 31P-MRSI to investigate regional energetic-mechanical coupling as a target for metabolic cardiac therapies. ### Competing Interest Statement The authors have declared no competing interest. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was performed in compliance with relevant laws, regulatory frameworks and guidelines where the research took place. This study was approved by the East of England - Cambridge South Research Ethics Committee. (Approval No. 23/EE/0048 ) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The 31P-MRSI analysis code, including the adapted OXSA toolbox and AHA segment assignment pipeline, is publicly available at [GitHub/GitLab repository URL to be inserted upon acceptance]. The anonymised participant data is available from the senior author upon reasonable request, subject to institutional data governance approval and a formal data transfer agreement. Horizon Europe, 101058229 NIHR Cambridge Biomedical Research Centre, NIHR203312 Medical Research Council, https://ror.org/03x94j517, MR/M009041/1, MR/M008983/1, UKRI2679, UKRI790
