Diagnosing chronic liver disease in primary care: developing a cost effective care pathway

Liver problems in people in the both the UK and internationally are becoming increasingly common. A number of experts in the field of liver disease study (hepatology) have called for early-identification of liver disease in the UK population, however there are large gaps in our knowledge about how to identify who will develop advanced liver disease (scarring, known as fibrosis) and in whom it will progress to cirrhosis and complications including liver failure and liver cancer.

Until recently the 'best' way of diagnosing liver scaring was by liver biopsy. An unpleasant procedure using a needle to obtain a sample of liver tissue. Over the past ten years there have been large advances in the development of non-invasive ways of measuring scarring such as blood tests and imaging. It has been suggested that these tests could be used to identify patients in primary care with liver disease earlier. We are currently unable to do this because of a number of factors, for example, we don't know how well these non-invasive tests work in the general population as they have been developed in selected hospital groups and we don't know how many people might be diagnosed with liver disease in order to plan appropriate follow-up care.

This fellowship proposal aims to address many of the missing elements in order to develop a cost effective diagnostic pathway for early-identification of liver disease in primary care in the UK. A number of projects are planned in order to develop the knowledge needed to do this.

Firstly, using a large routinely collected primary care data source (the Clinical Practice Research Datalink) I will estimate the impact of introducing different diagnostic tests for early-identification on patients and health service resources.

Secondly, using the same dataset I will compare the rate of liver complications (such as liver cancer) in the patients I have determined to have liver disease using non-invasive tests with the general population.

Thirdly, I will use a clinical study (the Nottingham Community (NCC) Study, also known as The Scarred Liver Project) to collect information about patients' quality of life. The NCC is offering high risk patients a specialist liver scan to diagnose scarring. I will measure these patients quality of life before their imaging and after to discover the impact having a diagnosis of liver disease has on them.

Together this new knowledge will allow me to estimate the impact of different strategies for early-identification on the frequency of liver disease diagnoses, rates of complications, impact on quality of life, and impact on behaviour. Together with information on the costs to the health service of different approaches to early-identification I will then determine the most efficient way to implement early identification of liver disease in primary care.

The results will guide the future clinical management of patients. I have already engaged with and have the support of a wide range of professionals who are involved in commissioning and developing clinical pathways in order to ensure the results of this work are implemented.

Rationale: CLD is one of the few diseases with an increasing incidence/prevalence both in the UK and internationally. Three independent UK reports have highlighted the need for the early detection of liver disease including the Chief Medical Officer report (2012), the All-Party Parliamentary Hepatology Group Inquiry and the Lancet commission in 2014.

Overall aim: To develop a cost-effective diagnostic strategy for CLD in primary care in the UK.

Methodology:
-The Clinical Practice Research Datalink (CPRD) will be used to phenotype CLD using easily available abnormal liver fibrosis/cirrhosis measures (AST/ALT ratio, APRI, FIB4, NAFLD Fibrosis Score) and to determine high risk target groups.
-Rates of CLD related complications over 5 and 10 years will be determined as relative and attributable risks associated with the non-invasive measure phenotyped CLD compared to the general population.
-Through primary data collection the Nottingham Community Cohort (NCC) Study will be used to collect and analyse health related quality of life data, pre- and post CLD diagnosis.
-Finally all components will be brought together in a cost-effectiveness assessment of different diagnostic strategies for CLD. The costs and benefits of alternative primary care pathways for identifying CLD against current practice will be modelled. A number of patient and societal effects are anticipated and data will be collected for analysis including: HRQoL, productivity, disease burden and health service costs and savings

Scientific and medical opportunities: This research will improve the applicability and reliability of clinical guidelines for the diagnosis of CLD in primary care. It will identify the most cost-effective strategy for integration into clinical care, with the intension of improving quality of care and outcomes for patients.

This fellowship proposal spans all three knowledge domains in the path to delivering impact: knowledge production, knowledge translation, knowledge exchange.

Given the aging population, diabetes and obesity epidemics and ongoing issues with alcohol consumption liver disease is a large and growing public health problem. Under the 2012 Health and Social Care Act, central government has given local authorities a core role in public health, with dedicated funding, supported by Public Health England. Additionally, to further support communities, Clinical Commissioning Groups (CCGS), made up of local general practitioners hold the purse strings and decide how to spend on healthcare. Not only will each of these stakeholders be impacted by this proposal directly through knowledge and actions on liver disease, but improving overall public health has significant economic impacts for industry and prosperity alongside reducing health inequalities

More specifically, this fellowship proposal has the potential to make a number of impacts:
-Policy-makers: Beyond the local and national UK interest in better understanding the use of non-invasive markers in the diagnosis of CLD this research is of interest globally. All Western countries are seeing an increase in CLD and none are currently in a position to take action due to this knowledge gap. It is essential that public health policies are driven by a sound evidence base in order to increase both the quality and effectiveness of services.
-Decision makers/budget holders: Parties commissioning healthcare services (e.g. CCGs) will benefit from local/national policy on liver disease care pathways in order to inform their spending and make cost-effective decisions.
-Commercial beneficiaries: Developers of existing or future liver fibrosis markers have the potential to be identified by this work.
-Third sector: A number of charities have an interest in liver health. For example, the British Liver Trust is a frontline organisation, communicating knowledge to the public. They provide information through a number of resources including their website which covers topics such as 'testing and screening' for liver disease. Providing the new information will strengthen their position in advocating for patients and assist with meeting their vision of 'best possible liver health for all'. This work will also inform the strategies of other groups e.g. British Society Gastroenterology, British Association for the Study of the Liver.
-Patients and the wider public: People at risk of liver disease have clear potential to benefit from this proposal through future screening for liver disease. This will in turn lead to their improved health and quality of life through a reduction in individual emergency admissions and complications of CLD.
-University of Nottingham: Building on existing skills and input from national/international experts, I will develop a research group with expertise in efficiently using routine data sets and health economics to answer applied health service research questions. My development with these skills and as an independent researcher will fill a current gap and build capacity to produce a team capable of being a resource for public and commercial researchers wishing to use this approach at other sites within the UK and Internationally. This area of work fits in with the goals of the Division of EPH to generate 'research which leads to positive changes in policy and practice across a range of clinical and public health research priority areas'.

All gains and impacts related to this proposal are foreseeable in the short to medium term (within 5 years of completion of the fellowship).