#FGDebate: Should we focus on detecting patients at risk of liver disease in the community?

Introduction

The #FGDebate series featured ‘Controversies in detecting patients with liver disease’ which was inspired by the recent review from Macpherson et al.¹ The debate was well attended and generated 1.35 million impressions across Twitter, which placed it within the top 10 #FGDebate of all time for total impressions made. The main topic for debate was whether we should focus on detecting patients at risk of liver disease in the community. Here, we aim to provide arguments for and against this issue.

Pro

What is the landscape our patients find themselves in? Liver disease is a major cause of morbidity in the UK and one of the leading causes of death in 35–49 years.² The national trainee collaborative, ToRcH-UK, involving 1168 patients with decompensated liver disease, across 104 acute trusts in UK, demonstrated 1 in 6 inpatients died during their admission.³ Over 70% of new liver disease presents acutely to hospital, many dying without the chance to change.⁴

The aim must be to reduce morbidity and mortality from liver disease. The two major leading causes of this are alcohol-related liver disease (ArLD) and non-alcoholic fatty liver disease (NAFLD), both preventable liver diseases with early intervention. Detecting liver disease early to facilitate specialist input, lifestyle and pharmacological interventions, may provide a genuine opportunity to prevent patients developing decompensated cirrhosis and hepatocellular carcinoma. While we lack prospective data, focusing on identification of patients with advanced fibrosis (ie, ≥F3 fibrosis), and thus at greater risk of future decompensating events, provides patients with the control to make supported lifestyle changes. For example, informing patients with alcohol misuse they have liver injury has been shown to trigger a substantial reduction in weekly alcohol consumption.⁵ By detecting and managing advanced fibrosis early, we can reduce admissions and mortality from liver disease while alleviating the burden on transplant services.

The standard of care for detection of liver disease has been opportunistic testing by primary care physicians who suspect their patient has liver disease. This is both inefficient and costly. Community-based early detection strategies have consistently demonstrated superiority over ‘standard of care’ for detection of advanced fibrosis.^6–9 Why advanced fibrosis and not just cirrhosis? Even in NAFLD, historically considered a slowly progressing fibrotic process,¹⁰ trial data has demonstrated over a fifth of patients with nonalcoholic steatohepatitis and F3 fibrosis progressed to cirrhosis within 2 years.¹¹ Furthermore, in studies that performed cost-effectiveness analyses, benefit over ‘standard of care’ was demonstrated.^{7 12 13} This was further supported by cost-comparison modelling of different strategies for detection fibrosis, supporting a two-step risk stratification model,¹⁴ now incorporated in international guidance.¹⁵

Early detection strategies need to be accompanied by public health strategy targeting liver disease to maximise their impact. Alcohol support services have been decimated in the last 12 years, which needs addressing. Minimum unit pricing for alcohol, shown to be effective in Scotland and Wales at reducing alcohol purchases,¹⁶ is a glaring omission from the public health strategy in England. Finally, detecting liver disease in the community is not solely the responsibility of primary care. Gastroenterologists and hepatologists must collaborate with primary care colleagues to support and identify patients with clinically significant fibrosis.

Clearly, the status quo is not working for our patients. Prospective data are vital but we already know much of what needs to be done. Detecting liver disease in patients at greatest risk early is a pragmatic and logical solution to prevent patients developing complications of liver disease and will reduce mortality.

Con

Early detection of liver disease is a key recommendation of the EASL-Lancet Commission¹⁷ and is supported by the UK Liver Alliance. Early detection offers the opportunity to introduce lifestyle measures and treatments which may, in theory, alter the trajectory of disease thereby reducing morbidity and mortality. The principal issues to tackle in early detection of liver disease in persons at risk are first; whether there is clinical benefit to the diagnosis of liver disease, and second; whether the costs of detection are justified by that benefit.

The vast majority of liver disease in the UK is a result of extremely common risk factors. One in five adults drink alcohol excessively¹⁸ and a quarter fall into the obese category,¹⁹ making the number of patients who would fulfil potential criteria for early detection interventions extremely large. The burden of this testing would fall largely to primary care clinicians, many of whom are already working beyond capacity, and this requires strong evidence to support its implementation. In addition, commonly used non-invasive tests to identify patients at increased risk of advanced fibrosis, such as FIB-4 and the NAFLD fibrosis score, are poorly validated in the primary care setting and performance may be inferior to that seen in secondary care.²⁰

Ultimately, the beneficial impact of detection or diagnosis of liver disease depends entirely on a change in treatment that favourably alters the trajectory of disease. There are no specific treatments for the patient with fatty liver due to ArLD or NAFLD and no or minimal fibrosis that depend on the diagnosis of liver disease. Reductions in alcohol consumption or dietary interventions are already recommended for those individuals to improve general health and reduce other complications of these comorbidities, questioning the impact of diagnosis. Furthermore, there is no clear evidence that the diagnosis of liver disease favourably impacts behaviour change and, in the largest primary care-based study in the UK (BALLETS) there was no net change in body weight following a diagnosis of NAFLD.²¹ In the absence of specific treatment and the absence of a favourable impact of diagnosis on behaviour change it is difficult to justify the detection of all patients with liver disease.

With potentially only marginal benefits in the detection of liver disease, it is critical to consider the costs of this approach. Without doubt, the testing strategies being advocated (and supported by national guidance) will carry substantial costs in financial terms, as well as in terms of patient and clinician time. For the most common liver diseases, in early stage, the overall number of patients who will go on to decompensate is unequivocally low over the medium or even longer term. There is therefore the risk of harm to the patient of receiving a diagnosis that in many cases will carry no clinical benefit.²² In the BALLETS study, there was a decrease in health-related quality of life following a diagnosis of fatty liver. While this did recover over time, it is clear that there is the potential for substantial harm in the population if we make a diagnosis of NAFLD in the estimated 14.1 million prevalent patients in the UK.²³

A focus on early detection alone will result in unnecessary investigations for the majority of individuals with the potential for harm, and at substantial cost. Rather than focusing on detection of patients at risk of liver disease in general, we need to move towards identifying those most likely to develop clinically relevant events, while clarifying if the interventions we offer these individuals improve outcomes at a population level. This requires prospective randomised evaluations with long-term follow-up to determine the clinical and cost-effectiveness of early detection approaches.

Conclusions

While there are key differences in both sides’ arguments (table 1), it is important to first acknowledge areas where both agree. Liver disease in the UK is driven by both ArLD and NAFLD. Both of these diseases are preventable with alcohol cessation and obesity management strategies undoubtedly leading to improvement in health beyond risk of liver disease complications. Detection of liver disease by the opportunistic finding of abnormal liver blood tests is unsatisfactory and can lead to under diagnosis as well as overinvestigation of otherwise well individuals.

Table 1.

Arguments pro and con detecting patients at risk of liver disease in the community

PRO	CON
UK liver disease morbidity and mortality is driven by preventable aetiologies	No specific liver disease intervention for early disease
Early recognition would allow for interventions to prevent these diseases	Risk of harm (particularly quality of life) of a diagnosis in patients with limited risk of liver-related complications
Community-based screening programmes are more likely to detect advanced fibrosis than standard of care and may be cost-effective	Increased financial cost and an increase burden of work to an already stretched primary care service

Early detection strategies have shown superiority in the detection of patients with advanced fibrosis compared with the use of opportunistic abnormal liver blood tests. However, with more patients highlighted as ‘at risk’, there will be an increased burden at both primary and secondary care level to ensure these patients are appropriately assessed and risk stratified. We must acknowledge the potential harm of a diagnosis of liver disease in patients at low risk of complications and aim to mitigate this within any pathway. Early detection strategies have the potential to reduce morbidity and mortality from chronic liver disease but require further finesse to allow for optimal implementation across the UK. Undoubtedly, prospective randomised controlled evaluations with appropriate follow-up will provide further pertinent information to implement these strategies.

Ethics statements

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