Author information
1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford and NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
2Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford and NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Barts Liver Centre, Queen Mary University London and Barts Health NHS Trust, London, UK.
3Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
4Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford and NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Oxford Liver Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; UK NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
5Royal Berkshire Hospital NHS Foundation Trust, Reading, UK.
6NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK.
7Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
8Leeds Liver Unit, St James's University Hospital Leeds, Leeds, UK.
9Institute of Translational and Stratified Medicine, University of Plymouth, Plymouth, UK.
10National Institute for Health Research Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham, UK.
11Barts Liver Centre, Queen Mary University London and Barts Health NHS Trust, London, UK; Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
12Oxford Liver Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; UK NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
13Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford and NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. Electronic address: Jeremy.tomlinson@ocdem.ox.ac.uk.
Abstract
Objectives: Currently, non-invasive scoring systems to stage the severity of non-alcoholic fatty liver disease (NAFLD) do not consider markers of glucose control (glycated haemoglobin, HbA1c); this study aimed to define the relationship between HbA1c and NAFLD severity in patients with and without type 2 diabetes.
Research design and methods: Data were obtained from 857 patients with liver biopsy staged NAFLD. Generalized-linear models and binomial regression analysis were used to define the relationships between histological NAFLD severity, age, HbA1c, and BMI. Paired biopsies from interventional studies (n = 421) were used to assess the impact of change in weight, HbA1c and active vs. placebo treatment on improvements in steatosis, non-alcoholic steatohepatitis (NASH), and fibrosis.
Results: In the discovery cohort (n = 687), risk of severe steatosis, NASH and advanced fibrosis correlated positively with HbA1c, after adjustment for obesity and age. These data were endorsed in a separate validation cohort (n = 170). Predictive modelling using HbA1c and age was non-inferior to the established non-invasive biomarker, Fib-4, and allowed the generation of HbA1c, age, and BMI adjusted risk charts to predict NAFLD severity. Following intervention, reduction in HbA1c was associated with improvements in steatosis and NASH after adjustment for weight change and treatment, whilst fibrosis change was only associated with weight change and treatment.
Conclusions: HbA1c is highly informative in predicting NAFLD severity and contributes more than BMI. Assessments of HbA1c must be a fundamental part of the holistic assessment of patients with NAFLD and, alongside age, can be used to identify patients with highest risk of advanced disease.