Prospectively mapping the development of liver disease amongst young adults. Who is developing it early and why?

Rationale

Historically, cirrhosis (irreversible liver scarring), often due to alcohol-related liver disease (ARLD) and non-alcoholic fatty liver disease (NAFLD), presents in the 5th and 6th decade. 1 in 6 inpatients die during hospital admission (1), with over 70% of new liver disease presenting acutely, many dying without the chance to change their lifestyle (2).

Liver disease presents is now one of the leading causes of death in 35-49 year olds, overtaking suicide (3). Early detection of liver disease is crucial to prevent progression to advanced disease and facilitate treatment. Young adults represent the next frontier in tackling the public health crisis of liver disease (4). In this regard, the Avon Longitudinal Study of Parents and Children (ALSPAC) is uniquely placed to provide normative data and evaluate the rising burden of liver disease.

When aged 17 years, ALSPAC participants were offered liver scans to assess NAFLD, revealing a 2.7% prevalence (5). When aged 24 years, 20.7% of participants had steatosis and 1 in 40 had liver scarring, the precursor to cirrhosis (6). Our participants are now 30 and over 4000 are set to receive further liver scan measurements.

Aims & Objectives

1. Estimating prevalence of NAFLD and ARLD in young adults in the general population aged 30 years.

2. Studying early life course determinants to understand why some participants are developing liver scarring earlier than others.

3. Evaluating if existing polygenic risk scores can be used to detect and predict individuals with subclinical liver scarring.

Methods

Examining and presenting normative data from the 30 year liver clinic to determine the prevalence of NAFLD and ARLD amongst ALSPAC participants. Use of linear and logistic regression to explore the strength of associations of common exposures associated with liver disease e.g. alcohol use, body mass index and sociodemographics. Mapping progression of disease from participants who had fibrosis aged 24 years.

Using the existing data within ALSPAC with outcomes of steatosis and fibrosis across ages 17, 24 and now 30 years, evaluate if there are sensitive periods for an impact of change in, or accumulation of, exposures including adiposity, cardiometabolic factors, and alcohol on liver steatosis/fibrosis at 30 years and its progression from 17 to 30 years. This will involve linear and logistic regression modelling and interaction analyses.

Finally, polygenic risk scores for detection of chronic liver disease exist (7). Using existing genomic data from ALSPAC, work will be done to explore if such scores are useful in this different ages (17, 24, 30 years), and whether they can be combined with clinical markers to improve detections and prediction of liver fibrosis.

How to apply for this project

This project will be based in Bristol Medical School - Population Health Sciences in the Faculty of Health Sciences at the University of Bristol.

If you have secured your own sponsorship or can self-fund this PhD please visit our information page here for further information on the department of Population Health Science and how to apply.