Nottingham Community Liver Biomarkers Cohort

Objectives:

• To establish a community based cohort with risk factors for liver disease and stratification for liver disease severity using non-invasive biomarkers.
• To establish the incidence of liver and cardiovascular morbidity and mortality in a community cohort.
• To explore the quantitative and qualitative indicators to potential alterations in patient lifestyle following stratification of liver disease to inform future intervention development.
• To evaluate novel blood markers of liver fibrosis and cirrhosis on a large cohort of primary care patients

Study Configuration:

Longitudinal Cohort Study with long-term follow up

Setting:

Primary Care, Nottingham

Number of Participants:

Prospective and consecutive recruitment in the East Midlands - approximately 500 patients per annum over a 4 year cohort inception period. Total anticipated cohort size 2,000 participants.

Description of Interventions:

• Serum blood sampling (AST:ALT ratio, and serum stored for future liver biomarker development)
• Transient Elastography (Fibroscan)
• Qualitative Interviews (limited to approximately 30 patients)
• Consent to longitudinal data follow-up and approach for future lifestyle intervention trials - consenting patients will be tagged on MRIS database.

Duration of Study:

48 month cohort inception with long term longitudinal follow up of cardiovascular and liver related outcomes and mortality data.

Outcome Measures:

• Incidence of liver (cirrhosis) and cardiovascular disease (symptomatic coronary or cerebrovascular disease).
• All cause morbidity and mortality.
• Quantitative and qualitative lifestyle measures (including body mass index, exercise levels, alcohol consumption).

Patients who decide to participate in the community cohort will not be required to perform any specific actions or attend study visits (unless for the reasons stated below). Usual clinical care (both liver-related and non-liver related) will continue during the study period.

Patients will consent to long term longitudinal data follow-up using the Medical Research Information Service (MRIS) database. All patients enrolled in the community cohort will be prospectively tagged on MRIS. In particular, the investigators will request individual patient alerts on MRIS concerning prevalent cardiovascular disease events (angina, myocardial infarction and stroke), liver cirrhosis and cause of death.

Patients will consent to undertake qualitative research to evaluate the process of community stratification. A purposeful sample of patients completing the community biomarkers pathway will be invited to participate in qualitative follow up of their experiences of the pathway and any subsequent lifestyle change. A researcher, trained in qualitative research methods, will perform a semi-structured interview, which will assess any lifestyle changes occurring following liver pathway stratification. Specifically, changes in alcohol consumption, diet and exercise will be explored and evaluated, with assessment of the relationship to liver pathway stratification (both investigation results and lifestyle advice offered during the pathway). Interviews will performed either face-to-face, in which case this will be performed at the Nottingham Digestive Diseases Biomedical Research Unit, or over the telephone - in all cases voice recording will occur to allow analysis of information provided. An example interview proforma to be utilized for these qualitative interviews has been provided separately.

Patients will be consented to donate biosamples (including blood and urine) to the Nottingham Health Sciences Biobank on inception into the cohort. An appointment will be made at the NIHR Nottingham Digestive Diseases Biomedical Research Unit for witnessed written consent and to allow donation of biosamples. Samples will be collected by trained research nurses, who also form part of the research team. These biosamples will be utilized for future research into novel biomarkers of liver and cardiovascular disease, including proteomics and metabonomics. Where participants do not agree to the future use of the samples they will be destroyed in accordance with the Human Tissue Act, 2004.

In the future, the investigators will plan trials assessing novel exercise and dietary interventions, and subsequent effects on patient lifestyle parameters and future cardiovascular risk. Patients forming the community cohort will consent for contact regarding these future trials; however individual trials will be subject to their own ethical approval and written consent.

Inclusion criteria

• Adult patients aged 18 years or over (male or female) with primary risk factor for liver disease:

• Hazardous alcohol use (>14 units/week for women, >21 units/week for men)
• Type 2 Diabetes
• Obesity
• Persistently elevated ALT with normal liver serology

Exclusion criteria

• Active malignancy at study enrolment
• Inability to provide informed consent for study enrolment
• Known presence of histologically proven liver disease prior to pilot pathway participation