Non-alcoholic fatty liver disease in young adults

: exploring burden and risk factors for early development

Abstract

Non-alcoholic fatty liver disease (NAFLD) is now one of the leading causes of liver disease across the world and has recently overtaken viral hepatitis as the second commonest indication for a liver transplant in the UK. However this condition is often considered a disorder of the 4th-6th decade and little is known about its prevalence and drivers in young adults.

Using clinic data collected from the Avon Longitudinal Study of Parents and Children (ALSPAC), the results of over 4000 transient elastography assessments were examined, performed on participants when they were 24 years old. The overall prevalence of steatosis and fibrosis was 20.7% and 2.7% respectively. The prevalence of NAFLD fibrosis specifically was 2.4%, but the participants with the highest odds of fibrosis were those with both alcohol use disorder and steatosis.

Following this the effect of early life exposures on offspring NAFLD development were examined, including longer and exclusive breastfeeding duration (≥6months), as well as maternal pre-pregnancy body mass index (BMI). No association was found with breastfeeding duration and outcomes of offspring NAFLD, but maternal pre-pregnancy BMI was strongly associated with outcomes of offspring NAFLD. A causal inference for an in utero effect was strengthened through a parental negative control test which confirmed a greater effect of maternal pre-pregnancy BMI on offspring NAFLD compared to paternal BMI.

Finally, the predictive ability of models consisting of different clinical measures collected in adolescents to determine future NAFLD fibrosis risk was explored in participants with an overweight or obese standardised BMI. BMI with sex, had the greatest explanatory power for understanding future risk of NAFLD fibrosis. A decision curve analysis was performed comparing different models in adolescents with an overweight standardised BMI. The model with the greatest net benefit was the model including all routine clinical measures, although the net benefit was marginal, equivalent to 5 more NAFLD fibrosis cases being detected per 1000 patients.

Date of Award	12 May 2022
Original language	English
Awarding Institution	University of Bristol
Supervisor	Matt Hickman (Supervisor), Jon E Heron (Supervisor), Fiona H Gordon (Supervisor) & James Orr (Supervisor)