Metabolic dysfunction associated steatotic liver disease (MASLD)

As part of the Hepatology Research Group
Non-alcoholic fatty liver disease
Paralleling the increasing prevalence of obesity, diabetes mellitus, and the metabolic syndrome in the general population, metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common cause of chronic liver disease worldwide. 
MASLD represents a spectrum of long-term conditions characterised by fat deposition in the liver. In the UK, MASLD is the most prevalent cause of chronic liver disease, estimated to affect 1 in 3 adults. 
The liver receives 75% of its blood flow directly from the intestinal portal circulation and due to the strong anatomical link between the gut and the liver, it is suggested that gut dysbiosis affects hepatic function and contributes to the pathogenesis of MASLD.
To this extent, the gut-liver axis has emerged as being critical to understanding the mechanisms and previously hidden aetiologies of liver disease progression. Early onset of MASLD and disease severity has been linked to high levels of TMAO, PAA, TCA and GCA in mice and humans. Investigating the impact of these gut metabolites and harmful bile acids in lipid accumulation is an important step for further understanding MASLD pathogenesis. 
Led by Dr David Sheridan we have been working in exposing different MASLD models to gut metabolites. We have been optimising Precision cut liver slices (PCLS) from human liver samples. PCLS are an emerging state-of-the-art technology where thin slices are prepared from liver resections sustained in tissue culture. These slices are extremely versatile and an ideal tool to investigate MASLD development and progression.
Non-alcoholic fatty liver disease. Preparation and incubation of liver slices

Non-alcoholic fatty liver disease. Preparation and incubation of liver slices

Alcohol-related liver disease

Rates of hospital admissions and deaths from alcohol-related liver disease (ARLD) have been steadily increasing for several decades. Despite this, there is inadequate research attention and activity in this field. The Hepatology Research Group aims to bridge the gap with a programme of translational research.
We are conducting a variety of projects to tackle important research questions. We aim to answer the following:
  • how can we predict response to treatment and outcome in people with alcohol-related hepatitis?
  • what are the barriers to accessing treatment for people with ARLD?
  • is treatment with functional imagery training effective in people with ARLD and alcohol use disorder?
  • what are the important research priorities in the field of ARLD?
  • how can we tackle stigma and how can we improve inclusion and engagement in people with ARLD?
Find out about our ongoing work in more detail below. Contact the theme lead, Dr Ashwin Dhanda for more information or to get involved.

Projects

Minimising mortality from alcohol-related hepatitis (MIMAH)

This MRC-funded precision medicine consortium, led from Imperial College London, aims to identify new biomarkers and treatments for alcohol-related hepatitis, an acute inflammatory liver disease with a high risk of mortality. The only treatment currently available is steroids but many patients don’t respond to this. We are working on a new bioassay to measure steroid responsiveness in people with this condition. We are also trying to understand mechanisms of steroid resistance, looking at changes in epigenetic regulation.
We have recently investigated markers of immune dysfunction as predictors of survival in people with alcohol-related hepatitis. We have shown that a measure of global immune function predicts survival and infection.
Together with Dr Lynne Callaghan, we are conducting semi-structured interviews with people with alcohol-related hepatitis recruited to a cohort study. We are trying to understand their experience of living with alcohol-related liver disease and how to reduce barriers to access treatment.

Mental Imagery to Reduce alcohol-related harm in people with alcohol dependence and alcohol-related liver damAGE (MIRAGE)

In collaboration with Professor Jackie Andrade, we have just completed this pilot randomised trial of Functional Imagery Training (FIT) in people with alcohol use disorder and alcohol-related liver disease. In the study funded by the Jon Moulton Charity Trust, we have shown that FIT can be delivered by NHS workers but that we need better support to engage participants in the trial and the treatment. Further feasibility work is ongoing before proceeding to a definitive trial.

An alcohol-related liver disease (ARLD) multi-stakeholder hub (ARMS-Hub) to improve and enhance research in under-served population in the UK

Dr Dhanda leads this NIHR-funded liver disease research partnership that is bringing together professionals from different disciplines and people with lived experience of ARLD to prioritise research questions and co-design studies to address these. We have a particular focus on themes of stigma, inclusion and engagement. The team are holding a series of virtual meetings in 2023 and 2024.