Non-alcoholic fatty liver disease (NAFLD) is the term used for a build-up of fat in the liver, in the absence of significant alcohol intake. Risk factors are thought to include obesity and diabetes. It is estimated that up to one in every three people in the UK may have early stages of NAFLD. NAFLD may progress to liver scarring (non-alcoholic steatohepatitis - NASH), ultimately causing liver failure (cirrhosis). The underlying inflammation in the liver may be a further risk factor for heart disease and cancer, due to the important roles of the liver in a number of pathways including the immune system, cholesterol metabolism and blood thinning regulation. We will use a large database of electronic health records to explore a) how common NAFLD is and how often it progresses to significant liver scarring c) whether NAFLD is associated with a range of cardiovascular diseases and cancers d) how people with NASH cirrhosis use healthcare services. Our findings, may allow for new screening strategies in individuals at risk of these conditions.
Non-alcoholic fatty liver disease (NAFLD) exists within a syndrome of disturbed metabolism, including increased total body adiposity, insulin resistance, impaired glucose tolerance and dyslipidaemia. NAFLD covers a spectrum of lesions ranging from steatosis to a complex pattern of hepatocellular injury and inflammation (non-alcoholic steatohepatitis [NASH]) in the absence of substantial alcohol intake. NAFLD is associated with an increased risk of mortality, with cardiovascular disease (CVD) being the most common cause; increasingly, NAFLD is also emerging as a risk factor for pre-malignant and malignant disease; the validation of NAFLD as a significant additional risk factor would have direct relevance for primary preventive strategies. We will use linked primary care, hospitalisation, disease registry and mortality data in England, to investigate associations of NAFLD with progression to cirrhosis and hepatocellular cancer, as well as incident cardiovascular disease and malignancies. We will include people aged 18 or older, with no prior liver disease or excess alcohol use. We will use time series analysis to compare incidence of disease between individuals with and without NAFLD/ NASH. Since NAFLD exists within a metabolic syndrome we will also examine the healthcare utilisation of individuals with NASH cirrhosis as an important secondary outcome measure. Our findings may be used to design new screening strategies in individuals at risk of these conditions.
Primary Outcomes:
1) All-cause mortality
2) Liver related mortality
3) Cardiovascular related mortality
4) Cancer related mortality
5) Disease progression to liver cirrhosis or hepatocellular carcinoma
Secondary Outcomes:
1) Incidence rates of cardiovascular disease (stable angina, unstable angina or coronary disease not further specified, heart failure, non-fatal myocardial infarction, peripheral arterial disease, ischaemic stroke, aortic aneurysm, arrhythmia/sudden cardiac death, unheralded coronary death). Cardiovascular phenotype definitions based on the CALIBER data sources are curated on the CALIBER data portal (https://caliberresearch.org/portal).
2) Incidence rates of non HCC malignancies (lung, breast, renal, prostate, pancreas, oesophageal, colorectal)
3) Healthcare utilisation in patients with cirrhosis (phenotypes relating to admissions will be required including varices, hepatic encephalopathy, hepatocellular carcinoma, ascites, spontaneous bacterial peritonitis, liver transplantation, jaundice)
Harry Hemingway - Chief Investigator - University College London ( UCL )
Constantinos Parisinos - Corresponding Applicant - University College London ( UCL )
Alvina Lai - Collaborator - University College London ( UCL )
Amitava Banerjee - Collaborator - University College London ( UCL )
Anoop Shah - Collaborator - University College London ( UCL )
Arturo Gonzalez-Izquierdo - Collaborator - University College London ( UCL )
Emmanouil Tsochatzis - Collaborator - University College London ( UCL )
Hanane Issa - Collaborator - University College London ( UCL )
Jane Elizabeth Carolan - Collaborator - University College London ( UCL )
Michail Katsoulis - Collaborator - Farr Institute of Health Informatics Research
Sheng-Chia Chung - Collaborator - University College London ( UCL )
Spiros Denaxas - Collaborator - University College London ( UCL )
Suvi Harmala - Collaborator - University College London ( UCL )
HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation