Endorsements

1.1 According to current estimates, 20–25% of the global adult population is affected by NAFLD, and an estimated 20% of people with NAFLD will develop NASH. However, robust epidemiological estimates, disaggregated by fibrosis stage, age, gender, risk profile and geographical area, are limited. Incomplete data hinder concerted action at the national and global levels.

1.2 Data from central registries, electronic health- care records or official statistics are available for certain countries and can be useful sources of information. However, differences in reporting, including the use of different administrative codes (for example, the International Classification of Disease (ICD) codes), limit comparability.

1.3 Data on paediatric NAFLD are scarce. Prevalence estimates vary widely, whilst there is limited information on long- term health outcomes in children living with NAFLD. However, available data indicate that NAFLD is an increasing problem in paediatric populations and is especially prevalent in children with obesity.

1.4 A wide range of factors needs to be considered in developing prevention and treatment approaches for NAFLD. These factors extend from metabolic risks, including insulin resistance, to genetic, social and environmental influences that may play a part in the development and progression of the disease.

1.5 NAFLD shares a bidirectional relationship with other metabolic conditions. Addressing NAFLD will likely reduce the prevalence and severity of these conditions.

1.6 There are both economic and social arguments for taking action on NAFLD. Evidence shows that NAFLD progression is associated with substantial health- care costs, socioeconomic losses and reduced quality of life, most notably in patients with advanced fibrosis and cirrhosis. Early intervention could help reduce the burden of disease, associated health- care costs and economic losses.

2.1 Communicating about NAFLD and its consequences has proved to be a major challenge for the liver health community.

2.2 Raising the profile of NAFLD as a public health issue will require clear messages about the condition, its consequences and what action is required. These messages should be tailored to specific audiences, including the liver and gastroenterology communities, primary care providers, specialists from other relevant disciplines, as well as stakeholders such as at- risk groups, the media and policy- makers.

2.3 Primary care providers and diabetes specialists can play a critical part in identifying and referring patients with advanced fibrosis to liver specialists. Raising the awareness of these medical providers would improve their ability to play this part.

3.1 Given the broad disease spectrum of NAFLD and the different levels of care required by patients across this spectrum, having clearly defined, context- specific models of care will be important for addressing the disease burden

3.2 The majority of people living with NAFLD can be managed in primary care; only patients with advanced disease need referral to a liver specialist. NAFLD care pathways can guide care decisions, including decisions on when to refer a patient to specialist care.

3.3 People living with NAFLD, especially those with advanced fibrosis, commonly require the management of multiple comorbid conditions, including diabetes, obesity and cardiovascular disease.

3.4 There is limited evidence on the impact of different NAFLD models of care on patient outcomes and cost- effectiveness. The lack of evidence and of investment in implementation research continues to impede the design and delivery of good care in different health- care settings and contexts.

3.5 Fibrosis stage is an important predictor of long- term liver- related outcomes and overall mortality in people living with NAFLD. Evidence of advanced fibrosis is an adequate indicator of a patient’s need for referral to specialist liver care.

3.6 Non- invasive tests (NITs) can be effective at excluding advanced fibrosis and the need for further assessment or referral to specialist liver care, especially when combinations of NITs are used sequentially.

3.7 The availability and use of different NITs vary among health- care settings. Non- comercial blood- based scores could be feasibly implemented in most primary and secondary care settings, such as diabetes clinics, if they were more readily available and widely known.

3.8 People living with type 2 diabetes mellitus (T2DM) and/or obesity are recognized as being at high risk for NAFLD- related complications. Collaboration and coordination across the different components of the health- care system will be needed to care for these patients most effectively

3.9 The natural history of paediatric NAFLD is poorly understood, due to a lack of prospective studies and the complex nature of the disease, including pathologies that are unique to children living with NAFLD. Better data on the natural history, pathophysiology and risk factors for disease progression would improve the care of this population.

3.10 Models of care for children should address all care needs, including the provision of psychological support, and be designed to facilitate the smooth transfer of care from paediatric to adult services.

3.11 The lack of validated NITs for use in children is a barrier to timely diagnosis and linkage to care.

3.12 Available data show that paediatric NAFLD is associated with both hepatic and non- hepatic morbidity and mortality. Children living with NAFLD might benefit from multidisciplinary management approaches tailored to their unique health- care needs.

3.13 In low- resource settings, the availability of diagnostic tools — including NITs — is likely to be limited, especially the more expensive imaging- based tests. Diagnosis in these settings will often require practitioners to make pragmatic choices and resort to low- cost solutions.

3.14 NAFLD is not mentioned in the current guidelines from the WHO on the detection, diagnosis and treatment of major non- communicable diseases (NCDs) in primary care in low- resource settings. Inclusion of NAFLD in such guidance would help to improve care for affected populations in these settings.

4.1 Interventions aimed at modifying lifestyle risk factors are the cornerstone of NAFLD treatment. There is some evidence that these interventions can prevent disease progression and can, in some cases, reverse fibrosis, yet more data will help to identity the most effective approaches and how to implement them in clinical practice.

4.2 As the number of effective pharmacological treatments for NAFLD increases, programmes aimed at modifying lifestyle risk factors will continue to be a core element of NAFLD disease management.

4.3 Access to treatment programmes for NAFLD requires that they be incorporated into relevant national health- care policies and guidelines and be adequately funded. Private and public payers and/or funders have a key part to play in ensuring financial support (for example, reimbursement) for these services.

4.4 The invasive nature of liver biopsy, the inherent variability of histological findings and the lack of an alternative validated surrogate for long- term clinical benefit have complicated the development of efficacious treatments for NAFLD.

5.1 People living with NAFLD can provide valuable insights into the design and implementation of interventions to safeguard and improve their health. Patients and patient organizations should be actively involved in developing policies and strategies to address NAFLD; however, few such groups currently address NAFLD.

5.2 Given that NAFLD is a largely invisible public health issue, high- profile patients can be especially useful in creating awareness and advocating for greater action on prevention and treatment.

5.3 Professional and patient organizations that address NCDs, including T2DM, obesity, heart disease and cancer, can play an important part in raising the profile of NAFLD, including by providing information to at- risk groups.

5.4 Stigma can be a major barrier when seeking to address health issues. Liver disease in general is commonly associated with unhealthy alcohol use, while NAFLD is associated with obesity. Both of these associations are with highly stigmatized conditions, and the implications of such stigma need to be acknowledged and addressed when developing prevention and treatment approaches for NAFLD.

6.1 A national strategy for NAFLD is lacking in almost every country in the world, while NAFLD is explicitly mentioned in very few national strategies or clinical guidelines for related conditions such as obesity or diabetes. This fact highlights the extremely low priority the condition has in national health agendas, and the need for a concerted effort to shape and deliver a robust public health response.

6.2 Several highly prevalent NCDs share common risk factors — such as unhealthy diets, physical inactivity and unhealthy alcohol consumption — with NAFLD. Policies, fiscal measures and legislation could address many of these diseases in a coordinated, simultaneous way.

6.3 Addressing NAFLD will require collective action that spans diverse disciplines and sectors. Existing frameworks such as the United Nations Sustainable Development Goals (SDGs) can usefully inform and guide the development of multi- sectoral efforts to address the direct, underlying and cross- cutting causes of NAFLD.

7.1 National and regional liver associations, in collaboration with governments and other stakeholders, have a leading role in responding to NAFLD, including in developing public health strategies and guidelines and in collaborating with other disease associations and organizations.

7.2 Multilateral organizations such as the WHO also have a key role in shaping and helping lead the response to NAFLD, firstly by recognizing the condition as a major health issue, and secondly by supporting nationally led efforts to deliver public health responses.

7.3 Global efforts to expand universal health coverage and ensure that health systems are people- centred provide a useful mechanism for holistically addressing NCDs, including not only NAFLD, but also associated diseases such as diabetes and obesity.

1 Investment is needed in research that will improve understanding of NAFLD epidemiology, especially in under- studied population groups such as children, and people without overt metabolic risk factors.

2 In the absence of population- based and prospective longitudinal studies, alternate research methods should be considered, such as those employing electronic health records.

3 Investment cases should be developed for NAFLD at global, regional and local levels. To support these cases, toolkits should be prepared to provide guidance on obtaining the requisite economic data and communicating the findings to policy- makers, health- care funders and/or payers and other relevant stakeholders.

4 Professional societies and other relevant stakeholders, such as patient organizations, should collaborate on a transparent process to carefully reconsider the nomenclature of fatty liver diseases, with special attention to the benefits of and barriers to changing the name of ‘non- alcoholic fatty liver disease’.

5 The liver health community should engage health communication experts to jointly develop effective strategies and practical tools to increase awareness in key audiences, including the media and policy- makers.

6 The terminology and concept of ‘compensated advanced chronic liver disease’ should be adopted, as it better reflects the continuum of advanced disease and the increased risk of decompensation than the current usage of fibrosis stages 3 and 4.

7 Professional bodies should develop simple knowledge products and educational courses targeting the liver and gastroenterology communities, primary care providers and specialists from other disciplines, as well as at- risk populations, the media and policy- makers. The courses should include medical school and continuing medical education activities.

8 Health- care planners and providers should design and implement locally feasible NAFLD care pathways, utilizing available tests to efficiently determine a patient’s care needs and link them to appropriate services.

9 Health- care providers — especially primary care providers, diabetes specialists and those caring for people living with obesity — should be equipped with the tools and knowledge needed to support the care of people living with NAFLD. At a minimum, providers should be able to identify which patients require referral to a liver specialist.

10 Multidisciplinary care models should form the basis for managing people living with NAFLD, especially those with advanced fibrosis.

11 Research should focus on developing more effective and more accurate non- invasive tests (NITs) for risk- stratifying patients — including children — in primary care, and for staging fibrosis and diagnosing NASH in secondary care.

12 Implementation research should be undertaken to better understand the barriers to uptake of currently available NITs.

13 Active case finding should be considered in population groups at high risk for advanced fibrosis. The specific target populations ought to be determined locally but should include people living with type 2 diabetes mellitus and central adiposity.

14 Implementation research is needed to identify the core elements of effective NAFLD care models in different health- care settings — including low- resource settings — and to provide generalizable findings that can inform the development of models of care in different.

15 Preventing and treating childhood NAFLD should be a priority, both as a means of improving child health and as a way of reducing the burden of disease in later life.

16 Research should focus on identifying interventions, including lifestyle treatments (for example, diet and physical activity regimens) and pharmacological treatments that can help people living with NAFLD and obesity to achieve and sustain a weight loss of at least 10%.

17 Effective structured lifestyle treatment programmes should be made available to people living with NAFLD, especially those who are at high risk of advanced fibrosis and/or rapid fibrosis progression.

18 Currently accepted surrogate histological end points for conditional NASH drug approval should be standardized, with the goal of eventually replacing them with non- invasive diagnostic and surrogate end point biomarkers.

19 Medical associations and other stakeholders should support patient groups in meeting the needs of people living with NAFLD. Where possible, NAFLD- specific groups should be formed. Patient groups focused on related conditions — including diabetes and obesity — should be provided with relevant information on NAFLD to share with their members.

20 Patient groups for liver disease and related non- communicable diseases (NCDs) should be involved in the development of clinical practice guidelines for NAFLD. Medical associations should also support these patient groups in developing relevant materials on NAFLD for their members.

25 A global coalition of organizations and individuals should lead the development of a NAFLD public health roadmap and support the global health community in following it.

26 Medical societies that provide care for any aspect of metabolic syndrome should formally collaborate to address NAFLD, including by jointly developing guidelines, policy briefs and plans

21 Efforts to detect, prevent and treat NAFLD should be integrated within a broader package of cost- effective interventions that holistically address NCD risk factors, focusing specifically on unhealthy diets, physical inactivity and unhealthy alcohol consumption.

23 The WHO should dedicate a World Health Day (7 April) to liver health to highlight the global prevalence of NAFLD and its significance for public health.

22 Global health organizations (including the WHO) and national institutions should incorporate NAFLD into their technical materials on NCDs and include NAFLD among their priority NCDs.

24 The NAFLD prevention agenda should include the creation of healthier, more equitable and sustainable societies as one of its core goals. One way to do that should be to emphasize the SDG targets that are relevant to preventing and treating NAFLD.