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Liver Disease Call Specification Document


Published: 10 May 2024

Version: 1.0 - May 2024

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The National Institute for Health and Care Research (NIHR) invites high quality, evaluative, applied healthcare research proposals to address important and enduring evidence gaps in liver disease research through the following research funding programmes:

Proposals should support health and care services to facilitate joined up care, helping people with liver disease to access the best advice, treatment and care possible.


In recognition of the need to support the building of capacity and capability in liver disease research, and to ensure that NIHR research is conducted in geographical areas and with populations where health and social care needs are greatest, NIHR commissioned 15 Liver Disease research partnerships across the UK in 2022. Details of these can be found in the supporting information document (available on request from

Most liver disease is preventable – only about 5% of deaths are attributable to autoimmune and genetic disorders – and over 90% are due to 3 main risk factors: alcohol, viral hepatitis and obesity. The last decade has witnessed significant advances in the management of viral hepatitis, and in particular cure rates for hepatitis C have increased dramatically. Despite this, liver disease mortality has increased by over 250% since 1971 in contrast with mortality from the other major causes of premature mortality (diabetes, cancer, heart disease etc.) which has reduced. [The 2nd Atlas of Variation in risk factors and healthcare for liver disease in England: September 2017]

People in deprived groups in England are more likely to develop, be hospitalised by, and die from liver disease than the most affluent. There is a negative correlation between deprivation and age of death. Notably, there is a 9 year gap between the median age at death for patients with liver disease residing in the 5 most deprived areas (62 yrs) compared to those from the least deprived 5 (71 yrs). This is even more pronounced for deaths from alcohol-related liver disease, where there is a 6 year gap between the 5 most (53 yrs) and least (59 yrs) deprived areas.

These deprived areas where disease burden is greatest have invariably been the same areas where research has traditionally not been conducted. In its 5th report, The Lancet Standing Commission on Liver Disease in the UK (Williams et al, 2018) highlighted the growing burden of liver disease. It included a financial analysis estimating the full societal costs for alcohol misuse – including crime, lost productivity, and child services – to be circa £21 billion per year in England and Wales (although this figure could be as high as £52 billion). The report also noted that for obesity, the total cost to society was circa £27 billion per annum, with some estimates as high as £45 billion.

It can take many years for liver disease to progress to a stage where symptoms develop and/or there is an impact on quality of life. Increasing levels of obesity, type 2 diabetes and alcohol consumption all have significant implications for a future increase in associated liver disease prevalence. Increasing collaboration through truly multidisciplinary partnerships and integrating care between and across health and care services (for people of all ages, as this is not just a disease of older people) has potential to make significant impact to what is a large group of patients.

Key information

Please note that this funding opportunity is open to researchers from across the UK, regardless of whether they received NIHR Research Partnership funding. However, applicants submitting proposals to this funding opportunity that did receive NIHR Research Partnership funding must make reference to this in both Stage 1 and Stage 2 application forms, to enable us to track progress.

General questions about the funding opportunity and programme remits may be obtained by sending a short summary (max 1 A4 page) of the proposal to the following address:

Four NIHR research programmes will be participating in this funding opportunity, and applications that span the remit of one or more of the following programme are welcomed. Proposals that fall outside of the overarching programme remits involved in this funding opportunity may be suitable for other NIHR funding programmes. Therefore, applicants are advised to pay close attention to the information in the links below about programme remit and tips for success:

Areas of particular interest

Areas of particular interest with outstanding evidence gaps include, but are not limited to:

Reducing health inequalities

  1. Applications addressing differences in outcomes, as well as inequity of access to high quality care, preventative interventions, and research.

Identification strategies and engagement between services

  1. Strategies to identify patients with liver disease, or at high risk of developing liver disease, at earlier stages in their natural history, including non-invasive testing and determination of cost-effectiveness
  2. Evaluation of integrated pathways between primary and secondary care as well as public health and social care, including long-term data follow-up and consideration of referral pathways

Behavioural interventions

  1. For prevention and for post diagnosis self-management, including brief interventions, use of technology and consideration of the determinations of durability of effect

What to do once liver disease has been identified

  1. Delivery of secondary care after admission with liver disease (e.g. care bundle to prevent re-admission)
  2. Appropriate management in primary care

Non alcohol related fatty Liver

  1. Diagnostic tests/biomarkers
  2. Prevention and management
  3. Evaluation of new treatments/precision medicine


  1. Identification strategies, particularly in underserved groups


  1. Prevention and management of fatty liver
  2. Management of chronic liver disease(s) including transition to adult services, particularly in those with other long term/chronic conditions

Services and workforce

  1. Variation in access to services and evaluation of targeted interventions to reduce inequalities
  2. Communication and working across relevant general and specialist services (including information-sharing). This will include interface between central liver units and others from endoscopy to alcohol care teams, as well as wider services in the community.
  3. Evaluation of new models of care, including one-stop shops and new forms of multidisciplinary teams and outreach services
  4. Patient, carer and staff experience of service delivery and models of care
  5. Transitions of care and support for self-management, taking into account needs of vulnerable populations, carers and families
  6. Optimal skill mix, training and experience of workforce to support quality care, including role of specialist nurses and those providing care in the community for patients with liver disease and multimorbidity

Proxy measures for health

NIHR recognizes that it can take many years for symptoms or impact on quality of life to manifest in liver disease. Definitive proof of disease can often only be ascertained by invasive biopsy. Understandably the aim is to avoid such procedures wherever possible. Taken together, proxy outcome measures might therefore be needed in order to diagnose and/or monitor the development/changes in liver disease in an efficient, timely and non-invasive patient-centric manner. As such, for this particular call, the NIHR will consider the use of proxy outcome measures, for example, alcohol consumption and BMI. Such outcome measures need to be appropriately defined in the application and the link to health must be clearly justified.

Underserved communities

Specifically for the purposes of this funding opportunity, applicants are strongly encouraged to include geographic areas where liver disease is prevalent and where populations have historically been underserved by research activity, in order to ensure that NIHR research is conducted in the areas where health needs are greatest.

Information is included in the supporting documentation to illustrate the potential mismatch between levels of research and burden of disease. This can be explored in greater levels of detail through the NIHR Clinical Research Network Research Targeting Tool (Liver Disease), which has been created to support identification of the geographical mismatch between where research has historically been conducted and where health needs are greatest across the whole of the UK. This geographical information reinforces the need to expand research activity into under-represented areas, aligning with NIHR’s ambition to increase research taking place in underserved communities, and ultimately increase patient benefit through participation in research. Guidance on how to use the Targeting Tool is included in the supporting information document (available on request from

General guidance

For support developing applications, applicants are also encouraged to contact their local NIHR Research Support Service (RSS) or equivalent in the devolved administrations in the first instance. Early contact with Clinical Trials Units, if appropriate, will also be beneficial. A list of clinical trials units that prospectively expressed interest in participating in this funding opportunity are shown in the supporting information document (available on request from