MRC Enterprise Studentship (iCASE): An exploration of the Heart - Liver axis: using MRI to understand how and why measurements taken in the liver relate to adverse cardiovascular outcomes

About the Research

Aim:

To determine the pathophysiological mechanisms associated with changes in liver MRI biomarkers, and which relate to adverse cardiovascular outcomes.

Background:

Metabolic dysfunction associated steatotic liver disease (MASLD) is the hepatic manifestation of the metabolic syndrome. MASLD affects a quarter of the population globally and is associated with adverse cardiovascular outcomes. A variety of biomarkers of MASLD have been developed and these have been shown to predict all-cause mortality and liver related events. Our centre has been instrumental in the development of liver T1 and iron corrected T1 (cT1) as biomarkers of chronic liver disease in general and MASLD in particular. We are therefore particularly interested in the observation that liver T1 and cT1 are associated with adverse cardiovascular outcomes in the wider general population. Cross-sectional studies comparing cT1 to liver histology show that fibrosis and inflammation are the pathophysiological mechanisms related to the changes in cT1 in people with liver disease. However, it is unclear whether the same pathophysiology underpins the observed increase in liver T1 / cT1 in participants from the general population such those in the UK Biobank.

We have previously shown that in healthy people liver cT1 and T1 is closely associated with changes in fluid status and validated the ratio of the cross-sectional area of the inferior vena cava to the cross-sectional area of the aorta (IVC/Ao ratio) as a surrogate of fluid status. We therefore hypothesise that in the general population, changes in liver T1 / cT1 are most likely related to fluid congestion, that in turn may be related to subclinical heart failure with with preserved ejection fraction (HFpEF).

Plan of work:

1. UK Biobank study

We will use imaging data collected from more than 50,000 participants from the UK Biobank study to evaluate any associations between metrics of right ventricular function and liver T1 / cT1. We will assess whether T1 measured in other tissues has the same predictive value as cT1 measured in the liver. We will also evaluate the association between liver cT1 and IVC/Ao ratio. We will develop imaging analysis pipelines to allow the (semi-)automated analysis of large numbers of data sets. The fellow will therefore develop skills in image analysis including the use of machine learning tools.

2. In-depth evaluation of dynamic changes in liver T1 in people with heart failure and preserved ejection fraction (HFpEF)

We have previously shown that cardiac function in subclinical HFpEF is better evaluated during exercise, and we have established a cardiac MR (CMR) protocol to do this. We will recruit 20 patients with HFpEF to be assessed with our exercise CMR protocol. We will measure cardiac parameters and also liver T1 before and during exercise. We hypothesise that the right heart pressure increases during exercise (which defines HFpEF seen as RA dilation and reduced RV systolic augmentation on CMR during exercise) causes reduced liver venous drainage, and therefore liver congestion (leading to an increase in liver T1). This would be similar to the transient lung congestion that is now being described in HFpEF during exercise.

Value of the results:

Understanding the underlying pathophysiology that drives adverse cardiovascular outcomes will have significant implications on the choice of potential treatments and preventive strategies. In particular, evidence of an association between fluid congestion or subclinical cardiac dysfunction and adverse cardiac outcomes, but none, or only weak evidence of an association between liver inflammation or fibrosis and adverse cardiac outcomes will propel the adoption of treatments aiming to improve cardiac function over treatments aiming to address liver inflammation or fibrosis in the wider population.

Lead supervisor: Dr Michael Pavlides 

Co-supervisor: Prof. Oliver Rider

Commercial partner: Perspectum Ltd

Please note that Michael Pavlides  is also offering another project. You may apply for either or both of his standard and Enterprise projects but you must indicate which projects you wish to apply to by naming both the supervisor and project. For example Pavlides (standard) and Pavlides (enterprise).

Further information about MRC Enterprise Studentships can be found here: iCASE 2025 — University of Oxford, Medical Sciences Division