Progress is impossible without change: understanding the evolving nomenclature of steatotic liver disease and its effect on hepatology practice.

The American, European, and Latin American liver societies have proposed a change in the nomenclature we use to describe alcohol-related liver disease and non-alcoholic fatty liver disease. Additionally, a term encompassing both is now advocated: steatotic liver disease, which includes metabolic dysfunction associated steatotic liver disease (MASLD) and MASLD with greater alcohol consumption (MetALD). These classifications offer increased relevance for clinicians, researchers, and patients alike. In this Viewpoint, we discuss the basis for this nomenclature shift and how it was developed. We also explore the challenges that will be faced in the adoption of such change. The proposed change seeks to banish stigma associated with phrasing such as alcoholic and fatty. However stigma, particularly related to the term fatty, is culturally nuanced, and reflects different entities depending on location. If such a change is internationally accepted, there will be wide-reaching effects on practitioners in primary care and metabolic medicine, and on patients. We discuss those effects and the opportunities the nomenclature change could offer, particularly for patients with alcohol and metabolic risk factors who represent a group previously ignored by clinical trials.

Prevalence of Skeletal Fluorosis in Northern Tanzania: A Follow-Up Study.

OBJECTIVES: Skeletal fluorosis is a metabolic bone disease caused by excessive exposure to fluoride, predominantly through contamination of drinking water. This study aimed to identify all cases of skeletal fluorosis in Tindigani village situated in Northern Tanzania. This was done following changes in drinking water sources after a previous prevalence study in 2009 in this population. METHODS: In a door-to-door cross-sectional study of Tindigani village, a sample of residents was assessed for skeletal fluorosis and dental fluorosis. Diagnosis of skeletal fluorosis was based on pre-defined angles of deformity of the lower limbs. Dental fluorosis was diagnosed and graded using the Thylstrup and Fejerskov Index. Samples from current drinking water sources underwent fluoride analysis. RESULTS: Tindigani village had a population of 1,944 individuals. Of the 1,532 individuals who were screened, 45 had skeletal fluorosis, giving a prevalence of 3.3% (95% CI=2.4, 4.3). Dental fluorosis was present in 82.5% of those examined (95% CI=79.8, 85.3). Dental fluorosis was present in all individuals with skeletal fluorosis and at higher grades than in the rest of the population. Drinking water samples were collected from 28 sources. These included piped, surface, well, and borehole water sources. Fluoride concentrations ranged from 0.45-38.59 mg/L of fluoride. CONCLUSIONS: Skeletal fluorosis is an ongoing but preventable health problem in the current population. The delivery of sustainable low fluoride piped water to this community would be of clear health benefit. This has been addressed at a local level.

Exploring changing attitudes to non-invasive liver fibrosis tests in secondary care pathways: comparison of two national surveys.

Introduction: The increasing availability of non-invasive tests (NITs) has created the opportunity to explore their use in improving risk stratification of advanced liver disease. The study aimed to determine the attitudes and practices among UK secondary care specialists, focusing primarily on attitudes to fibrosis assessment and the use of NITs. Methods: Two web-based surveys were circulated, first between 2014 and 2015 (survey 1), and again in 2021 (survey 2). The surveys were promoted via the British Society of Gastroenterology, the British Association for the Study of the Liver and using Twitter. Results: In survey 1, 215 healthcare professionals (HCPs) completed the online survey. 112 HCPs completed survey 2. 71 acute UK trusts were represented in survey 1 compared with 60 trusts in survey 2. Between the two surveys, the proportion of HCPs performing fibrosis assessment in all or nearly all cases rose from 45.1% to 74.1% (χ2=25.01; p<0.0001). 46.5% (n=33/71) respondents in acute services reported the use of NITs in clinical pathways in survey 1, rising to 70.0% (n=42/60) in survey 2 (χ2=7.35; p=0.007). Availability of tests has increased but is not universal. The proportion reporting availability as a barrier to uptake fell from 57.2% of responses in survey 1 to 38.4% in 2021 χ2=11.01; p=0.0009). Conclusion: Between 2014 and 2021, the role of NITs in fibrosis assessment has risen substantially, as has the proportion of clinicians using NITs in clinical pathways to assess risk of liver disease. Poor access to NITs remains the predominant barrier.

Stratification Of LIver Disease (SOLID): protocol for a prospective observational cohort study to determine the optimum biomarker strategies for the detection of advanced liver disease at the primary-secondary care interface.

INTRODUCTION: Undiagnosed fatty liver disease is prevalent in the community, due to high rates of harmful alcohol consumption and/or obesity. Fatty liver disease can progress to cirrhosis and its complications. Early identification of liver disease and treatment may prevent progression to cirrhosis. Biomarkers including FIB-4, enhanced liver fibrosis (ELF), PRO-C3 and vibration controlled transient elastography (VCTE) can stage liver fibrosis, but it is not known how well they perform in a primary care population. Moreover, no assessment of long-term prognostic ability of these biomarkers has been conducted in primary care. We aim to evaluate the performance of fibrosis biomarkers in primary care to develop a pathway to detect advanced fibrosis. METHODS AND ANALYSIS: This prospective, observational cohort study will recruit 3000 individuals with fatty liver disease risk factors (obesity, type 2 diabetes or hazardous alcohol consumption) at their primary care 'annual chronic disease review'. Participants will have a 'liver health check'. Two pathways will be evaluated: (1) all have FIB-4, ELF and VCTE performed, and (2) patients have an initial assessment with FIB-4 and ELF, followed by VCTE in only those with increased FIB-4 and/or ELF. Individuals with suspected significant/advanced liver fibrosis (liver stiffness measurement>8 kPa), will be reviewed in secondary care to confirm their fibrosis stage and institute treatment. The performance of FIB-4, ELF, PRO-C3, VCTE and novel biomarkers alone or in combination for advanced fibrosis/cirrhosis will be evaluated. Participants will be followed longitudinally via their electronic health records to assess long-term clinical outcomes. ETHICS AND DISSEMINATION: Ethical approval was obtained from the London-Chelsea Research Ethics Committee (22/PR/0535; 27 June 2022). Recruitment began on 31 October 2022. Outcomes of this study will be published in peer-reviewed journals and presented at scientific meetings. A lay summary of the results will be available for study participants and will be disseminated widely by LIVErNORTH.

Liver disease management as routine work in primary care: a qualitative interview study to guide implementation.

BACKGROUND: Morbidity from liver disease is rising in the UK. Most cases are caused by alcohol or non-alcoholic fatty liver disease (NAFLD) and treatable if caught early. Liver disease pathways have been shown to increase detection in the community, but have not been adopted into routine primary care work. AIM: To explore primary care healthcare professional (HCP) experiences and understanding of chronic liver disease, and where it might fit into management of long-term conditions. DESIGN AND SETTING: Qualitative interview study with 20 HCPs in primary care in the north of England. METHOD: A semi-structured approach informed by a theory of implementation (normalisation process theory [NPT]). Data collection and analysis were concurrent. Interview data were analysed using thematic analysis. RESULTS: Participants identified the following key areas for action: incentivised frameworks and protocols to drive understanding, organise, and sustain practice; inclusion of common liver diseases into multimorbidity care to reduce complexity and workload; a need to define the GP role within a lifestyle-focused treatment pathway; and education/local champions to initiate and legitimise individual and organisational participation in change. CONCLUSION: To embed chronic liver disease management in routine primary care work, researchers and policymakers must be aware of the implementation challenges. These findings can guide the adoption of effective pathways and help bridge the implementation gap.

Quality standards for the management of non-alcoholic fatty liver disease (NAFLD): consensus recommendations from the British Association for the Study of the Liver and British Society of Gastroenterology NAFLD Special Interest Group.

Non-alcoholic fatty liver disease (NAFLD) is common, affecting approximately 25% of the general population. The evidence base for the investigation and management of NAFLD is large and growing, but there is currently little practical guidance to support development of services and delivery of care. To address this, we produced a series of evidence-based quality standard recommendations for the management of NAFLD, with the aim of improving patient care. A multidisciplinary group of experts from the British Association for the Study of the Liver and British Society of Gastroenterology NAFLD Special Interest Group produced the recommendations, which cover: management of people with, or at risk of, NAFLD before the gastroenterology or liver clinic; assessment and investigations in secondary care; and management in secondary care. The quality of evidence for each recommendation was evaluated by the Grading of Recommendation Assessment, Development and Evaluation tool. An anonymous modified Delphi voting process was conducted individually by each member of the group to assess the level of agreement with each statement. Statements were included when agreement was 80% or greater. From the final list of statements, a smaller number of auditable key performance indicators were selected to allow services to benchmark their practice. It is hoped that services will review their practice against our recommendations and key performance indicators and institute service development where needed to improve the care of patients with NAFLD.

Developing a primary care-initiated hepatitis C treatment pathway in Scotland: a qualitative study.

BACKGROUND: The ease of contemporary hepatitis C virus (HCV) therapy has prompted a global drive towards simplified and decentralised treatment pathways. In some countries, primary care has become an integral component of community-based HCV treatment provision. In the UK, however, the role of primary care providers remains largely focused on testing and diagnosis alone. AIM: To develop a primary care-initiated HCV treatment pathway for people who use drugs, and recommend theory-informed interventions to help embed that pathway into practice. DESIGN AND SETTING: A qualitative study informed by behaviour change theory. Semi-structured interviews were undertaken with key stakeholders (n = 38) primarily from two large conurbations in Scotland. METHOD: Analysis was three-stage. First, a broad pathway structure was outlined and then sequential pathway steps were specified; second, thematic data were aligned to pathway steps, and significant barriers and enablers were identified; and, third, the Theoretical Domains Framework and Behaviour Change Wheel were employed to systematically develop ideas to enhance pathway implementation, which stakeholders then appraised. RESULTS: The proposed pathway structure spans broad, overarching challenges to primary care-initiated HCV treatment. The theory-informed recommendations align with influences on different behaviours at key pathway steps, and focus on relationship building, routinisation, education, combating stigmas, publicising the pathway, and treatment protocol development. CONCLUSION: This study provides the first practicable pathway for primary care-initiated HCV treatment in Scotland, and provides recommendations for wider implementation in the UK. It positions primary care providers as an integral part of community-based HCV treatment, providing workable solutions to ingrained barriers to care.

Does moderate alcohol consumption accelerate the progression of liver disease in NAFLD? A systematic review and narrative synthesis.

OBJECTIVES: Liver disease is a leading cause of premature death, partly driven by the increasing incidence of non-alcohol-related fatty liver disease (NAFLD). Many people with a diagnosis of NAFLD drink moderate amounts of alcohol. There is limited guidance for clinicians looking to advise these patients on the effect this will have on their liver disease progression. This review synthesises the evidence on moderate alcohol consumption and its potential to predict liver disease progression in people with diagnosed NAFLD. METHODS: A systematic review of longitudinal observational cohort studies was conducted. Databases (Medline, Embase, The Cochrane Library and ClinicalTrials.gov) were searched up to September 2020. Studies were included that reported progression of liver disease in adults with NAFLD, looking at moderate levels of alcohol consumption as the exposure of interest. Risk of bias was assessed using the Quality in Prognostic factor Studies tool. RESULTS: Of 4578 unique citations, 6 met the inclusion criteria. Pooling of data was not possible due to heterogeneity and studies were analysed using narrative synthesis. Evidence suggested that any level of alcohol consumption is associated with worsening of liver outcomes in NAFLD, even for drinking within recommended limits. Well conducted population based studies estimated up to a doubling of incident liver disease outcomes in patients with NAFLD drinking at moderate levels. CONCLUSIONS: This review found that any level of alcohol intake in NAFLD may be harmful to liver health.Study heterogeneity in definitions of alcohol exposure as well as in outcomes limited quantitative pooling of results. Use of standardised definitions for exposure and outcomes would support future meta-analysis.Based on this synthesis of the most up to date longitudinal evidence, clinicians seeing patients with NAFLD should currently advise abstinence from alcohol. PROSPERO REGISTRATION NUMBER: The protocol was registered with PROSPERO (#CRD42020168022).

Engagement with community liver disease management across the UK: a cross-sectional survey.

BACKGROUND: Liver disease is an increasing cause of premature mortality in the UK. Its management in primary care is not well understood. It is unclear what role commissioning bodies are playing in liver disease in the UK. AIM: To assess the level of engagement with community chronic liver disease management among clinical commissioning groups (CCGs) and health authorities across the UK. DESIGN & SETTING: A cross-sectional survey to all UK CCGs and health authorities. METHOD: Survey questions were developed by the British Liver Trust, in collaboration with topic experts, and evaluated structures in place relating to liver disease management at commissioning and health board level. RESULTS: There were 159 responses representing 99% UK coverage of CCGs and health boards. Twenty per cent reported an individual responsible for liver disease within their organisation, with 40% and 29% reporting having pathways in place to respond to abnormal liver blood tests and liver disease more generally, respectively. All those reporting use of pathways reported using national guidelines to guide content. Twenty-five per cent made use of transient elastography (FibroScan) and 16% of direct serum fibrosis markers (for example, enhanced liver fibrosis [ELF] score), which are both part of current National Institute for Health and Care Excellence (NICE) guidelines. There was marked regional variation in all areas of engagement surveyed, with Wales having exceptionally high levels of engagement in all areas in contrast to the other nations. CONCLUSION: The results of this survey should be used as a catalyst to highlight necessary regional improvements to the primary care management of chronic liver disease across the UK.

Provider-related barriers and enablers to the provision of hepatitis C treatment by general practitioners in Scotland: A behaviour change analysis.

The ease of direct-acting antiviral (DAA) medications for hepatitis C virus (HCV) has provided an opportunity to decentralize HCV treatment into community settings. However, the role of non-specialist clinicians in community-based pathways has received scant attention to date. This study examined barriers and enablers to expanding the role of general practitioners (GPs) in HCV treatment provision, using simple behaviour change theory as a conceptual framework. A maximum variation sample of 22 HCV treatment providers, GPs and HCV support workers participated in semi-structured interviews. Data were inductively coded, and the resulting codes deductively mapped into three principal components of behaviour change: capability, opportunity and motivation (COM-B). By this process, a number of provider- and systemic-level barriers and enablers were identified. Key barriers included the pre-treatment assessment of liver fibrosis, GP capacity and the 'speciality' of HCV care. Enablers included the simplicity of the drugs, existing GP/patient relationships and the provision of holistic care. In addition to these specific factors, the data also exposed an overarching provider understanding of 'HCV treatment' as triumvirate in nature, incorporating the assessment of liver fibrosis, the provision of holistic support and the treatment of disease. This understanding imposes a further fundamental barrier to GP-led treatment as each of these three components needs to be individually addressed. To enable sustainable models of HCV treatment provision by GPs, a pragmatic re-examination of the 'HCV treatment triumvirate' is required, and a paradigm shift from the 'refer and treat' status quo.

Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. Many individuals have risk factors associated with NAFLD, but the majority do not develop advanced liver disease: cirrhosis, hepatic decompensation, or hepatocellular carcinoma. Identifying people at high risk of experiencing these complications is important in order to prevent disease progression. This review synthesises the evidence on metabolic risk factors and their potential to predict liver disease outcomes in the general population at risk of NAFLD or with diagnosed NAFLD. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis of population-based cohort studies. Databases (including MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov) were searched up to 9 January 2020. Studies were included that reported severe liver disease outcomes (defined as liver cirrhosis, complications of cirrhosis, or liver-related death) or advanced fibrosis/non-alcoholic steatohepatitis (NASH) in adult individuals with metabolic risk factors, compared with individuals with no metabolic risk factors. Cohorts selected on the basis of a clinically indicated liver biopsy were excluded to better reflect general population risk. Risk of bias was assessed using the QUIPS tool. The results of similar studies were pooled, and overall estimates of hazard ratio (HR) were obtained using random-effects meta-analyses. Of 7,300 unique citations, 22 studies met the inclusion criteria and were of sufficient quality, with 18 studies contributing data suitable for pooling in 2 random-effects meta-analyses. Type 2 diabetes mellitus (T2DM) was associated with an increased risk of incident severe liver disease events (adjusted HR 2.25, 95% CI 1.83-2.76, p < 0.001, I2 99%). T2DM data were from 12 studies, with 22.8 million individuals followed up for a median of 10 years (IQR 6.4 to 16.9) experiencing 72,792 liver events. Fourteen studies were included in the meta-analysis of obesity (BMI > 30 kg/m2) as a prognostic factor, providing data on 19.3 million individuals followed up for a median of 13.8 years (IQR 9.0 to 19.8) experiencing 49,541 liver events. Obesity was associated with a modest increase in risk of incident severe liver disease outcomes (adjusted HR 1.20, 95% CI 1.12-1.28, p < 0.001, I2 87%). There was also evidence to suggest that lipid abnormalities (low high-density lipoprotein and high triglycerides) and hypertension were both independently associated with incident severe liver disease. Significant study heterogeneity observed in the meta-analyses and possible under-publishing of smaller negative studies are acknowledged to be limitations, as well as the potential effect of competing risks on outcome. CONCLUSIONS: In this review, we observed that T2DM is associated with a greater than 2-fold increase in the risk of developing severe liver disease. As the incidence of diabetes and obesity continue to rise, using these findings to improve case finding for people at high risk of liver disease will allow for effective management to help address the increasing morbidity and mortality from liver disease. TRIAL REGISTRATION: PROSPERO CRD42018115459.

Unacceptable failures: the final report of the Lancet Commission into liver disease in the UK.

This final report of the Lancet Commission into liver disease in the UK stresses the continuing increase in burden of liver disease from excess alcohol consumption and obesity, with high levels of hospital admissions which are worsening in deprived areas. Only with comprehensive food and alcohol strategies based on fiscal and regulatory measures (including a minimum unit price for alcohol, the alcohol duty escalator, and an extension of the sugar levy on food content) can the disease burden be curtailed. Following introduction of minimum unit pricing in Scotland, alcohol sales fell by 3%, with the greatest effect on heavy drinkers of low-cost alcohol products. We also discuss the major contribution of obesity and alcohol to the ten most common cancers as well as measures outlined by the departing Chief Medical Officer to combat rising levels of obesity-the highest of any country in the west. Mortality of severely ill patients with liver disease in district general hospitals is unacceptably high, indicating the need to develop a masterplan for improving hospital care. We propose a plan based around specialist hospital centres that are linked to district general hospitals by operational delivery networks. This plan has received strong backing from the British Association for Study of the Liver and British Society of Gastroenterology, but is held up at NHS England. The value of so-called day-case care bundles to reduce high hospital readmission rates with greater care in the community is described, along with examples of locally derived schemes for the early detection of disease and, in particular, schemes to allow general practitioners to refer patients directly for elastography assessment. New funding arrangements for general practitioners will be required if these proposals are to be taken up more widely around the country. Understanding of the harm to health from lifestyle causes among the general population is low, with a poor knowledge of alcohol consumption and dietary guidelines. The Lancet Commission has serious doubts about whether the initiatives described in the Prevention Green Paper, with the onus placed on the individual based on the use of information technology and the latest in behavioural science, will be effective. We call for greater coordination between official and non-official bodies that have highlighted the unacceptable disease burden from liver disease in England in order to present a single, strong voice to the higher echelons of government.

Does older adults' use of social care influence their healthcare utilisation? A systematic review of international evidence.

Improving our understanding of the complex relationship between health and social care utilisation is vital as populations age. This systematic review aimed to synthesise evidence on the relationship between older adults' use of social care and their healthcare utilisation. Ten databases were searched for international literature on social care (exposure), healthcare use (outcome) and older adults (population). Searches were carried out in October 2016, and updated May 2018. Studies were eligible if they were published after 2000 in a high income country, examined the relationship between use of social care and healthcare utilisation by older adults (aged ≥60 years), and controlled for an indicator of need. Study quality and bias were rated using the National Institute of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Study data were extracted and a narrative synthesis was conducted. Data were not suitable for quantitative synthesis. Thirteen studies were identified from 12,065 citations. Overall, the quality and volume of evidence was low. There was limited evidence to suggest that longer lengths of stay in care homes were associated with a lower risk of inpatient admissions. Residents of care homes with onsite nursing had fewer than expected admissions to hospital, compared to people in care homes without nursing, and adjusting for need. Evidence for other healthcare use outcomes was even more limited and heterogeneous, with notable gaps in primary care. We conclude that older adults' use of care homes may moderate inpatient admissions. In particular, the presence of registered nurses in care homes may reduce the need to transfer residents to hospital. However, further evidence is needed to add weight to this conclusion. Future research should build on this evidence and address gaps regarding the influence of community based social care on older adults' healthcare use. A greater focus on primary care outcomes is imperative.

Gathering momentum for the way ahead: fifth report of the Lancet Standing Commission on Liver Disease in the UK.

This report presents further evidence on the escalating alcohol consumption in the UK and the burden of liver disease associated with this major risk factor, as well as the effects on hospital and primary care. We reiterate the need for fiscal regulation by the UK Government if overall alcohol consumption is to be reduced sufficiently to improve health outcomes. We also draw attention to the effects of drastic cuts in public services for alcohol treatment, the repeated failures of voluntary agreements with the drinks industry, and the influence of the industry through its lobbying activities. We continue to press for reintroduction of the alcohol duty escalator, which was highly effective during the 5 years it was in place, and the introduction of minimum unit pricing in England, targeted at the heaviest drinkers. Results from the introduction of minimum unit pricing in Scotland, with results from Wales to follow, are likely to seriously expose the weakness of England's position. The increasing prevalence of obesity-related liver disease, the rising number of people diagnosed with type 2 diabetes and its complications, and increasing number of cases of end-stage liver disease and primary liver cancers from non-alcoholic fatty liver disease make apparent the need for an obesity strategy for adults. We also discuss the important effects of obesity and alcohol on disease progression, and the increased risk of the ten most common cancers (including breast and colon cancers). A new in-depth analysis of the UK National Health Service (NHS) and total societal costs shows the extraordinarily large expenditures that could be saved or redeployed elsewhere in the NHS. Excellent results have been reported for new antiviral drugs for hepatitis C virus infection, making elimination of chronic infection a real possibility ahead of the WHO 2030 target. However, the extent of unidentified cases remains a problem, and will also apply when new curative drugs for hepatitis B virus become available. We also describe efforts to improve standards of hospital care for liver disease with better understanding of current service deficiencies and a new accreditation process for hospitals providing liver services. New commissioning arrangements for primary and community care represent progress, in terms of effective screening of high-risk subjects and the early detection of liver disease.

GPs' experiences and perceptions of early detection of liver disease: a qualitative study in primary care.

BACKGROUND: The incidence of liver disease is increasing in the UK and primary care is a key setting where improvement in the detection and management of liver disease is required. Little is known about GPs' understanding and confidence in detecting liver disease. AIM: To explore GPs' experiences of liver disease with a focus on early detection and interpretation of liver function tests (LFTs). DESIGN AND SETTING: A qualitative study employing semi-structured interviews of a purposive sample of GPs from five UK primary care study sites. METHOD: Telephone and face-to-face interviews of GPs were undertaken. Data were analysed thematically, using a constant comparative approach. RESULTS: From a total of 25 GP interviews (N = 25), four themes were identified from the data: test-requesting behaviour, confidence and challenges in diagnosing disease, access to specialist tests, and guidance and education. Participants' descriptions of how they request and interpret LFTs varied widely. Concern over missing diagnoses was a common reason for requesting blood tests; patients with mildly abnormal LFTs and those at risk of non-alcoholic fatty liver disease (NAFLD) were a particular cause of concern. GPs saw themselves as generalists, with a reluctance to take on specialist investigations. Guidelines promoted confidence for some clinicians, but others felt that liver disease was too complex to be amenable to simple instructions. Most felt that they did not have access to relevant, focused education on liver disease. CONCLUSION: Liver disease is not perceived as a priority in primary care. If GPs are to take on a greater role in identification and management of liver disease, support is needed to promote awareness, knowledge, and confidence.

How can primary care enhance end-of-life care for liver disease? Qualitative study of general practitioners' perceptions and experiences.

BACKGROUND: Liver disease is the third most common cause of premature death in the UK. The symptoms of terminal liver disease are often difficult to treat, but very few patients see a palliative care specialist and a high proportion die in hospital. Primary care has been identified as a setting where knowledge and awareness of liver disease is poor. Little is known about general practitioners' (GPs) perceptions of their role in managing end-stage liver disease. OBJECTIVE: To explore GPs' experiences and perceptions of how primary care can enhance end-of-life care for patients with liver disease. DESIGN: Qualitative interview study, thematic analysis. PARTICIPANTS: Purposive sample of 25 GPs from five regions of England. RESULTS: GPs expressed a desire to be more closely involved in end-of-life care for patients with liver disease but identified a number of factors that constrained their ability to contribute. These fell into three main areas; those relating directly to the condition, (symptom management and the need to combine a palliative care approach with ongoing medical interventions); issues arising from patients' social circumstances (stigma, social isolation and the social consequences of liver disease) and deficiencies in the organisation and delivery of services. Collaborative working with support from specialist hospital clinicians was regarded as essential, with GPs acknowledging their lack of experience and expertise in this area. CONCLUSIONS: End-of-life care for patients with liver disease merits attention from both primary and secondary care services. Development of care pathways and equitable access to symptom relief should be a priority.