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Gastrointestinal

Metabolic dysfunction-associated steatotic liver disease

Last revised in July 2026

Non-alcoholic fatty liver disease (NAFLD) refers to excess triglyceride accumulation in the liver (steatosis), in the absence of excessive alcohol

Metabolic dysfunction-associated steatotic liver disease (MASLD): Summary

  • Metabolic dysfunction-associated steatotic liver disease (MASLD) refers to excess fat (triglyceride) accumulation in the liver (steatosis), in the absence of excessive alcohol consumption.
    • Alcohol consumption of less than 20 g (2.5 units) per day for women, and less than 30 g (3.75 units) per day for men, is used as the cut-off to diagnose MASLD.
  • The term was previously non-alcoholic fatty liver disease (NAFLD).
  • MASLD encompasses a spectrum of liver disease strongly associated with insulin resistance.
    • Up to 90% of people have simple steatosis, where the prognosis is generally good.
    • Metabolic dysfunction-associated steatohepatitis (MASH) defines a subgroup of MASLD where there is a risk of progression to advanced liver fibrosis, cirrhosis, or rarely, hepatocellular cancer.
  • MASLD is often asymptomatic, but may occasionally cause non-specific symptoms of fatigue, general malaise, and abdominal discomfort.
  • MASLD is the commonest cause of abnormal liver blood tests in the UK.
  • Metabolic risk factors for MASLD include hypertension; impaired glucose regulation or type 2 diabetes mellitus; central obesity; and hyperlipidaemia.
  • Direct liver complications include portal hypertension, variceal haemorrhage, liver failure and hepatocellular carcinoma.
  • Metabolic complications include cardiovascular disease, impaired glucose regulation, and type 2 diabetes mellitus.
    • Cardiovascular disease is the most common cause of death in people with MASLD.
  • MASLD should be suspected if a person has:
    • Risk factors for MASLD.
    • At least 3 months elevation of alanine aminotransferase (ALT) levels (up to 3 times the upper limit of normal), exceeding aspartate aminotransferase (AST) levels.
    • Upper abdominal ultrasound scan findings consistent with fatty liver changes.
  • LFTs and liver ultrasound appearances may be normal in people with MASLD, and should not be used to exclude the diagnosis.
  • If MASLD is suspected:
    • Blood tests should be arranged to exclude alternative causes of liver disease and possible metabolic complications.
    • The risk of advanced liver fibrosis should be assessed using a non-invasive scoring system, such as the NAFLD Fibrosis Score (NFS), Fibrosis (FIB)-4 score or the Enhanced Liver Fibrosis (ELF) test.
    • The risk of cardiovascular disease should be assessed using a validated tool.
  • Management of MASLD in primary care includes:
    • Giving lifestyle modification advice about diet, physical activity, and regular exercise, to encourage gradual sustained weight loss, especially if a person is overweight or obese.
    • Advice about drinking alcohol within national recommended limits.
    • Ensuring that associated conditions such as hypertension, hyperlipidaemia, and type 2 diabetes mellitus are optimally managed.
    • Giving advice about sources of information and support for people with MASLD, such as the British Liver Trust.
  • Follow-up of a person with MASLD in primary care includes:
    • Examination for signs of advanced liver disease and checking body mass index and blood pressure.
    • Blood tests to assess for associated metabolic conditions.
    • Reassessment of the risk of cardiovascular disease annually and advanced liver fibrosis every 3 years.
  • Referral to a liver specialist should be considered if:
    • There is a high risk of advanced liver fibrosis.
    • There are signs of advanced liver disease.
    • There is uncertainty about the diagnosis.

Have I got the right topic?

From age 16 years onwards.

This CKS topic covers the diagnosis, management, and referral of people with metabolic dysfunction-associated steatotic liver disease (MASLD), including metabolic dysfunction-associated steatohepatitis (MASH).

This CKS topic does not cover the diagnosis and management of MASLD in children or pregnant women, the detailed investigation and management of people with MASLD in secondary care, or the diagnosis and management of liver disease associated with alcohol.

There are separate CKS topics on Chronic kidney disease, CVD risk assessment and management, Diabetes - type 2, Gallstones, Gilbert's syndrome, Hepatitis A, Hepatitis B, Hepatitis C, Hypertension, Jaundice in adults, Lipid modification - CVD prevention, and Obesity.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary healthcare.

How up-to-date is this topic?

Changes

July 2026 — minor update. Names changed to metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH).

Previous changes

October 2023 — minor update. A typographical error has been corrected.

August 2023 — minor update. A typographical error has been corrected.

July 2023 — minor update. A broken link to the FIB-4 calculator has been replaced. 

October 2021 — reviewed. Updated evidence on prevalence, aetiology, complications, diagnosis, and management.

July 2015 to October 2016 — new topic. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

Update

New evidence

Evidence-based guidelines

  • McPherson, S., Armstrong, M., Cobbold, J., et al. (2022) Quality standard 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. The Lancet. www.thelancet.com [Free Full-text]

HTAs (Health Technology Assessments)

No new HTAs since 1 October 2021.

Economic appraisals

No new economic appraisals relevant to England since 1 October 2021.

Systematic reviews and meta-analyses

No new systematic reviews and meta-analyses since 1 October 2021.

Primary evidence

  • Jang, H., Kim, Y., Lee, D. H., et al. (2024). Outcomes of Various Classes of Oral Antidiabetic Drugs on Nonalcoholic Fatty Liver Disease. JAMA Internal Medicine. [Abstract]

New policies

No new national policies or guidelines since 1 October 2021.

New safety alerts

No new safety alerts since 1 October 2021.

Changes in product availability

No changes in product availability since 1 October 2021.

Goals and outcome measures

Goals

To support primary healthcare professionals to:

  • Make a working diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) in primary care.
  • Assess a person with suspected MASLD including their risk of advanced liver fibrosis and cardiovascular disease.
  • Offer appropriate lifestyle advice and monitoring in primary care.
  • Refer people with MASLD to hepatology specialist, if appropriate, for further investigation and management.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

No QIPP indicators were found during the review of this topic.

NICE quality standards

No NICE quality standards were found during the review of this topic.

Background information

Definition

  • Primary metabolic dysfunction-associated steatotic liver disease (MASLD) refers to excess fat (triglyceride) accumulation in the liver (steatosis), where triglycerides are present in more than 5% of hepatocytes, which is not the result of excessive alcohol consumption or other secondary causes [NICE, 2016; Perumpail, 2017; Rikhi, 2020].
  • MASLD encompasses a spectrum of liver disease strongly associated with insulin resistance.
    • Up to 80% of people have simple hepatic steatosis [Perumpail, 2017].
    • MASLD ranges from hepatic steatosis, through metabolic dysfunction-associated steatohepatitis (MASH) where there is steatosis coexisting with hepatocellular injury and inflammation, with risk of progression to advanced liver fibrosis and cirrhosis [NICE, 2016]. 
  • Secondary MASLD may be caused by drug treatments such as amiodarone or tamoxifen [Younossi, 2016], hepatitis C virus infection, and endocrine conditions such as polycystic ovary syndrome [EASL-EASD-EASO, 2016].
  • MASLD is usually asymptomatic, but may occasionally cause non-specific symptoms of fatigue, general malaise, and abdominal discomfort [World Gastroenterology Organisation, 2014].

Prevalence

MASLD is now the commonest cause of abnormal liver blood test results in the UK [British Liver Trust & RCGP, 2016], and one of the most important liver diseases worldwide affecting adults and children. It is anticipated that it will become the leading reason for transplantation [Younossi, 2018]. The rise in prevalence of MASLD parallels the rise in the prevalence of obesity [Sattar et al, 2014].

  • The reported prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) varies in Europe on the definition of MASLD and the modality used to detect it, but generally reflects the prevalence of obesity in the population studied [Younossi, 2018]:
    • Prevalence increases with increasing age, and is highest in males aged 40–65 years.
    • Global prevalence of MASLD is estimated to be 24%.
    • Highest rates are in the Middle East (32%) and South America (31%).
    • The next highest rates are Asia (27%), United States (24%) and Europe (23%). Lower rates are found in Africa (14%).

MASLD is increasingly identified in non-obese individuals. Around 40% of the global MASLD population can be classified as non-obese, and 20% as lean [Ye, 2020].

Incidence data is very uncommon. A 2007 study from England reported the incidence according to ICD-10 classification as 29 per 100,000 person-years [Whalley et al, 2007] This figure is most likely a large underestimate for the current population.

Causes

  • The exact cause of metabolic dysfunction-associated steatotic liver disease (MASLD) is not fully understood, however it is likely to be closely linked to insulin resistance, obesity, and the metabolic syndrome [World Gastroenterology Organisation, 2014].
  • Environmental factors and genetic factors are inter-related. Evidence from familial and twin studies show a significant inheritable component to MASLD.
  • Gene loci have been identified that are associated with development and severity of MASLD in people of European descent [Mancina, 2016] Similar gene variants have been identified for Latino populations in South America [Chen, 2015].
  • Alcohol consumption and obesity are known to act synergistically to increase the risk of liver disease morbidity and mortality [Hart, 2010]

Risk factors

  • Metabolic risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD) include features of the metabolic syndrome that indicate increased cardiovascular risk  [EASL-EASD-EASO, 2016; NICE, 2016; Chalasani, 2018].
    • Central obesity — 91% of people with body mass index (BMI) greater than 30 kg/m2 or increased waist circumference (greater than 94 cm in men or 80 cm in women [in white people]) have been found to have MASLD [Bedogni et al, 2014]   —  see the CKS topic on Obesity for more information.
    • Impaired glucose regulation or type 2 diabetes mellitus (T2DM). Global prevalence of MASLD among people with T2DM is 55% [Ballestri, 2016a; Younossi, 2019]  — see the CKS topic on Diabetes - type 2 for more information.
    • Hypertension — see the CKS topic on Hypertension for more information.
    • Hyperlipidaemia (hypertriglyceridaemia and/or low high-density lipoprotein [HDL]-cholesterol level) — see the CKS topic on Lipid modification - CVD prevention for more information.
  • Other possible risk factors for MASLD include [NICE, 2016; Younossi, 2018]:
    • Obstructive sleep apnoea syndrome — see the CKS topic on Obstructive sleep apnoea syndrome for more information.
    • Endocrine disorders for example, Polycystic Ovary syndrome — see the CKS topic on Polycystic ovary syndrome for more information, Hypothyroidism — see the CKS topic on Hypothyroidism for more information and Growth Hormone deficiency.
    • A family history of MASLD.
    • Ethnicity — higher risk in Hispanic and Asian people, lower risk in black people.
    • Nutritional — total parenteral nutrition (TPN) and refeeding syndrome, rapid weight loss, and jejunoileal bypass surgery.
    • Drugs — for example nonsteroidal anti-inflammatory drugs, amiodarone, corticosteroids, diltiazem, methotrexate, and tamoxifen.
    • Other liver conditions, such as hepatitis C and Wilson's disease. See the CKS topic on Hepatitis C for more information.

Complications

  • Complications of metabolic dysfunction-associated steatotic liver disease (MASLD) include morbidity and mortality from liver and (more commonly) cardiovascular disease [EASL-EASD-EASO, 2016; ] :
    • Direct hepatic complications include:
      • Portal hypertension.
      • Variceal haemorrhage.
      • Liver failure.
      • Hepatocellular carcinoma (HCC).
      • Sepsis — the liver has a major role in host-defence mechanisms and the systemic response to severe infection, and is an important target organ in the development of multi-organ failure in sepsis.
      • These complications are rare even in untreated MASLD.
    • Metabolic complications:
      • People with MASLD are more at risk of developing hypertension, chronic kidney disease, impaired glucose regulation, and type 2 diabetes mellitus [NICE, 2016]. In people with type 2 diabetes, MASLD is a risk factor for atrial fibrillation, myocardial infarction, ischaemic stroke, and death from cardiovascular disease[Mantovani, 2018; Mantovani, 2019; Wijarnpreecha, 2020].
      • A meta-analysis of 28 prospective cohort studies assessing the association between MASLD and the risk of developing type 2 diabetes (20 studies, n = 117,020) and metabolic syndrome (8 studies, n = 81,411) over a median follow-up of 5 years, found that people with MASLD have an almost two-fold increased risk of type 2 diabetes and metabolic syndrome [Ballestri, 2016b].
    • Mortality from cardiovascular and liver disease:
      • Cardiovascular disease is the most common cause of death in people with MASLD —  a meta-analysis of 16 prospective and retrospective observational studies (n = 34,043) found that people with MASLD had a significantly higher risk of fatal and/or non-fatal cardiovascular events than those without MASLD (odds ratio 1.64; 95% CI 1.26–2.13) [Targher, 2016].

Prognosis

  • The prognosis of metabolic dysfunction-associated steatotic liver disease (MASLD) depends on the stage of disease and the presence of co-morbidities.
    • If a person is overweight or obese, or has type 2 diabetes mellitus, they are at increased risk of progressive disease [NICE, 2016].
    • If a person has simple steatosis, the prognosis is generally good — cirrhosis develops in 0–4% of people with simple steatosis over 10–20 years, there is very slow, if any, histological progression.
    • If a person has the sub-group metabolic dysfunction-associated steatohepatitis (MASH), they have an increased risk of progressive liver fibrosis, cirrhosis, liver failure, and hepatocellular cancer (HCC) [World Gastroenterology Organisation, 2014; Chalasani, 2018] The average age of a person with MASH is 40–50 years [NICE, 2016].
    • All cause mortality increases with increasing fibrosis stage [Dulai, 2017] Even fibrosis stage 1 has an increased risk of mortality.
    • Risk of mortality increases on an exponential scale, rather than linear, with increasing fibrosis.
    • Genetic background (PNPLA3 variation) might influence a person's ability to reverse fibrosis with exercise [Mantovani, 2021].
  • The most common cause of death in people with MASLD is cardiovascular disease, independent of other cardiovascular co-morbidities [Chalasani, 2018]

Diagnosis of metabolic dysfunction-associated steatotic liver disease

When should I suspect MASLD?

In most people, metabolic dysfunction-associated steatotic liver disease (MASLD) is detected incidentally when liver blood tests or an abdominal ultrasound scan are performed for some other reason.

  • Suspect a person has MASLD if they have:
    • Risk factors suggestive of the metabolic syndrome or other risk factors for MASLD such as obesity, dyslipidaemia or hyperglycaemia.
    • Persistent elevation of liver blood tests for 3 months or more — typically alanine aminotransferase (ALT) levels are raised up to 3 times the upper limit of normal, and exceed aspartate aminotransferase (AST) levels.
    • Absence of excess alcohol intake.
    • Upper abdominal ultrasound scan findings consistent with fatty liver changes (increased hepatic echogenicity). Ultrasound has a pooled sensitivity of 85% and specificity of 94% for moderate to severe steatosis [Zhou, 2019]
    • Negative blood tests for other causes of hepatic disease such as viral hepatitis, autoantibody screen, immunoglobulin titres, ferritin and transferrin saturation.
    • Do not use routine liver blood tests to rule out MASLD — be aware that liver blood tests and liver ultrasound appearances may be normal in people with MASLD and do not necessarily reflect the stage of disease.
  • Use a first-line non-invasive tool to assess the level of fibrosis, such as Fibrosis- 4 (FIB-4) or NAFLD Fibrosis Score (NFS). Patients with a low score can be managed in primary care.

Basis for recommendation

The recommendations on when to suspect metabolic dysfunction-associated steatotic liver disease (MASLD) are based on the National Institute for Health and Care Excellence (NICE) clinical guideline Non-alcoholic fatty liver disease (NAFLD): assessment and management [NICE, 2016], the European Association for the Study of the Liver EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease [EASL-EASD-EASO, 2016], guidelines by the British Liver Trust and the Royal College of General Practitioners (RCGP)- Non-alcohol-related fatty liver disease and its primary care management [British Liver Trust & RCGP, 2016], Practice Guidance from the American Association for the study of liver disease [Chalasani, 2018] and Guidelines on the management of abnormal liver blood tests [Newsome, 2018a]

 MASLD is usually detected incidentally

  • The information that MASLD is usually detected incidentally following liver blood tests or an abdominal ultrasound scan is based on expert opinion in the NICE guideline [NICE, 2016], and the American guideline [Chalasani, 2018] The EASL guideline also states that MASLD is the main reason for unexpectedly elevated liver enzymes [EASL-EASD-EASO, 2016].

Risk factors for MASLD

  • The recommendation to suspect MASLD if a person has risk factors is based on the fact that 70–90% of people with the metabolic syndrome have NAFLD, and metabolic syndrome is an independent predictor of liver fibrosis in people with MASLD [Dyson et al, 2014; Chalasani, 2018]
  • The NICE clinical guideline states that early detection of MASLD may be useful to identify people with potentially silent progressive fatty liver disease [NICE, 2016].
  • Clinical guidelines state that due to variation in cost-effectiveness of different imaging and non-invasive tests to diagnose MASLD in adults, and the uncertainty in the evidence base for using non-invasive tests, the use of a specific diagnostic test to screen for and identify MASLD in people with risk factors is not recommended [NICE, 2016; Chalasani, 2018]

Persistent elevation of liver function tests (LFTs)

  • The recommendation on suspecting MASLD if there is a persistent elevation of LFTs (particularly transaminases) for 3 months is based on a regional clinical guideline, which states that short-lived abnormal LFTs for a few weeks may be due to intercurrent illness which resolves [Hudson, 2014].

Ultrasound findings of fatty liver changes

  • The recommendation to suspect MASLD if there are changes on liver ultrasound scan are based on a number of clinical guidelines and review articles (as above), however it is noted that ultrasound is operator-dependent and is insensitive in detecting MASLD unless more than 33% of hepatocytes are steatotic [Dyson et al, 2014]. A normal liver appearance on ultrasound does not rule out mild fatty liver disease [Dyson et al, 2014].
  • There are a number of additional limitations in the use of ultrasound to diagnose MASLD and this is not a recommended approach. Ultrasound cannot distinguish MASH from simple steatosis [Sattar et al, 2014], or MASLD from alcoholic fatty liver disease. There are technical difficulties of performing ultrasound in people who are obese [Sattar et al, 2014], and the sensitivity and specificity of ultrasound for detecting fatty infiltration decreases as a person's body mass index increases, and varies from 49–100% and from 75–95% respectively [Adams et al, 2005].
  • The NICE clinical guideline does not recommend the use of ultrasound as a diagnostic test if MASLD is suspected, as this would require the referral of large numbers of people to secondary care, which would place an additional burden on ultrasound services [NICE, 2016].

Not using routine liver blood tests to rule out MASLD

  • This recommendation is based on the NICE guideline that although MASLD is a very common cause of abnormal liver blood tests, more than 80% of people with MASLD have normal routine liver blood tests. As a result, clinicians should not rely exclusively on liver blood tests to rule out MASLD [NICE, 2016; Newsome, 2018a]
  • LFTs do not correlate reliably with liver histology findings, and the full spectrum of MASLD-associated liver disease may be seen in people with normal LFT results  [NICE, 2016].

How should I assess a person with MASLD?

In a person with suspected metabolic dysfunction-associated steatotic liver disease (MASLD):

  • Ask about:
    • Any symptoms, such as fatigue and right upper quadrant abdominal pain.
    • Any risk factors for MASLD.
    • Alcohol intake — consumption of less than 20 g (2.5 units) per day for women, and less than 30 g (3.75 units) per day for men, is used as the cut-off to diagnose MASLD. If a person is drinking above these levels or has a history of heavy alcohol consumption, they may have alcoholic fatty liver disease.
    • Any co-morbidities and drug history — to assess for other secondary causes of fatty liver disease.
  • Examine the person:
    • Check height and weight (to calculate body mass index [BMI]), and waist circumference.
    • Check blood pressure.
    • Assess for signs of advanced liver disease (such as jaundice, spider naevi, palmar erythema, ascites, hepatomegaly, splenomegaly, hepatic encephalopathy), and if present, refer the person to a hepatology specialist for further assessment.
  • Arrange blood tests to exclude co-existing liver disease (if there are abnormal liver blood test results) and metabolic conditions, depending on clinical judgement.
    • Liver blood tests — there may be a raised bilirubin, a high aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, and low albumin in advanced liver fibrosis.
    • Full blood count — unexplained low platelets can be a sign of advanced liver fibrosis.
    • Clotting — may be deranged in advanced liver fibrosis.
    • Hepatitis B and C viral serology — check HBsAg and anti-HCV levels to screen for chronic viral hepatitis B and C respectively. See the CKS topics on Hepatitis B and Hepatitis C for more information.
    • Auto-antibodies — high titres of anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) may suggest autoimmune hepatitis, and high titres of anti-mitochondrial antibodies (AMA) may suggest primary biliary cirrhosis. Note: low titres of auto-antibodies may be an incidental finding in people with MASLD.
    • Ferritin (and transferrin saturation if ferritin is raised) — to screen for hereditary haemochromatosis.
    • Serum caeruloplasmin — consider checking for Wilson's disease if the person is less than 40 years of age.
    • Alpha-1-antitrypsin deficiency — consider checking for alpha-1-antitrypsin deficiency if there is a positive family history or associated respiratory symptoms, but be aware that liver involvement is rare in adults.
    • HbA1c — to screen for impaired glucose regulation or type 2 diabetes mellitus. See the CKS topic on Diabetes - type 2 for more information.
    • Lipid profile — to screen for hyperlipidaemia. See the CKS topic on Lipid modification - CVD prevention for more information.
    • Renal function tests — to screen for chronic kidney disease. See the CKS topic on Chronic kidney disease for more information.
    • Thyroid function tests — to screen for hypothyroidism. See the CKS topic on Hypothyroidism for more information.
    • Immunoglobulin (IgA) tissue transglutaminase antibody (tTGA) — coeliac disease can present with cryptogenic liver disease. See the CKS topic on Coeliac disease for more information.
  • Assess the risk of advanced liver fibrosis — do not use routine liver blood tests. Consider using a non-invasive scoring system, such as the:
    • NAFLD Fibrosis Score (NFS) — an intermediate or high score (greater than minus 1.455), suggests advanced liver fibrosis.
    • Fibrosis (FIB)-4 Score (FIB-4) — a score of greater than 2.67 suggests advanced liver fibrosis.
      • If the person is at high risk of advanced liver fibrosis, refer to a hepatology specialist for further assessment and management.
      • If the person is at low risk of advanced liver fibrosis, explain they are unlikely to have advanced liver fibrosis, and follow up the person in primary care.
    • Enhanced Liver Fibrosis (ELF) test — a score of 10.51 or above suggests advanced liver fibrosis.
  • Assess the person's risk of cardiovascular disease — see the CKS topic on  CVD risk assessment and management for more information.

Advanced liver fibrosis risk scores

The National Institute for Health and Care Excellence (NICE) recommends considering the use of the Enhanced Liver Fibrosis (ELF) test to assess the risk of advanced liver fibrosis in people with suspected metabolic dysfunction-associated steatotic liver disease (MASLD) [NICE, 2016]. Later recommendations also suggest using the NAFLD Fibrosis score (NFS) or the Fibrosis 4 score [Newsome, 2018a], [Royal College of General Practitioners, 2021a]. 

  • The ELF test is an algorithm that requires the measurement of hyaluronic acid, amino-terminal propeptide of type III procollagen (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP-1) [Buzzetti, 2015].
  • The NAFLD Fibrosis Score (NFS) (available at www.nafldscore.com) which comprises 6 easily measured variables (age, body mass index, blood glucose, platelet count, albumin, and aspartate aminotransferase [AST] to alanine aminotransferase [ALT] ratio) [Chalasani et al, 2012].
  • The Fibrosis 4 (FIB-4) Score (available at https://www.mdcalc.com/), which uses the person's age, AST, ALT, and platelet count, and has been developed to assess the risk of cirrhosis in people with hepatitis C and non-alcoholic steatohepatitis (NASH) [Dyson et al, 2014].

Basis for recommendation

The recommendations on how to assess a person with suspected metabolic dysfunction-associated steatotic liver disease (MASLD) are based on the National Institute for Health and Care Excellence (NICE) clinical guideline Non-alcoholic fatty liver disease (NAFLD): assessment and management [NICE, 2016], the European Association for the Study of the Liver EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease [EASL-EASD-EASO, 2016], Practice Guidance from the American Association for the Study of Liver Diseases[Chalasani, 2018], and the Royal College of General Practitioners Liver Disease Toolkit [Royal College of General Practitioners, 2021b].

Presenting symptoms

  • The information on possible presenting symptoms is based on the NICE clinical guideline [NICE, 2016] and a review article [Adams et al, 2005] which state that MASLD is usually asymptomatic, but can present with symptoms of fatigue and abdominal pain.

Assessing for risk factors

  • The recommendation to assess for risk factors for MASLD is based on the fact that the metabolic syndrome is a strong predictor for the presence of metabolic dysfunction-associated steatohepatitis (MASH) in people with MASLD [EASL-EASD-EASO, 2016; Younossi, 2019].

Taking an alcohol history

  • The recommendation to take an alcohol history to rule out alcohol-related liver disease is based on the NICE guideline [NICE, 2016], and the cut-offs cited to diagnose MASLD are based on the EASL clinical practice guidelines [EASL-EASD-EASO, 2016], and a review article on the diagnosis and staging of MASLD [Dyson et al, 2014]. The EASL clinical practice guidelines state that alcohol consumption up to 30 g for men and 20 g for women is insufficient to induce alcoholic steatohepatitis [EASL-EASD-EASO, 2016].
  • In addition, people consuming moderate amounts of alcohol may still be at risk of MASLD if they have metabolic risk factors [EASL-EASD-EASO, 2016].

Assessing body mass index (BMI), blood pressure, and for signs of advanced liver disease

  • The recommendation on checking the person's weight and BMI is based on the EASL clinical practice guidelines which state that central obesity can predict advanced fatty liver disease [EASL-EASD-EASO, 2016].
  • The recommendation on checking the person's blood pressure is based on the fact that a person with MASLD is more at risk of components of the metabolic syndrome, including hypertension, and the rate of progression of MASLD is doubled by the presence of arterial hypertension [EASL-EASD-EASO, 2016].
  • The recommendation on assessing a person for signs of progressive advanced liver fibrosis are based on the World Gastroenterology Organisation global guidelines [World Gastroenterology Organisation, 2014].

Considering blood tests to exclude co-existing liver disease and metabolic conditions

  • Guidelines from NICE, Newsome, The American Association for the Study of Liver Diseases , and the Royal College of General Practitioners recommend screening for alternative causes of liver disease in people who present with abnormal liver blood tests and suspected or confirmed fatty liver disease [NICE, 2016; Newsome, 2018b; Chalasani, 2018; Royal College of General Practitioners, 2021b].
  • Several guidelines highlight that a person may have co-existing liver disease, and some co-morbid conditions such as viral hepatitis may increase the risk of progression of MASLD and can increase the severity of liver fibrosis. In addition, MASLD can exacerbate liver damage in chronic hepatitis C, haemochromatosis, and alcoholic liver disease.
  • The information that low titres of auto-antibodies may be an incidental finding in people with MASLD is based on expert opinion in a review article [Vuppalanchi and Chalasani, 2009].
  • The EASL clinical practice guidelines recommend that all people with a fatty liver should be screened for features of the metabolic syndrome. The risk of impaired glucose regulation and type 2 diabetes is closely associated with the severity of MASLD [EASL-EASD-EASO, 2016], and poor blood glucose control increases the risk of fibrosis in people with metabolic dysfunction-associated steatohepatitis (MASH) [Younossi, 2016].
  • The recommendation to check renal function tests is based on the fact that people with MASLD are more at risk of developing chronic kidney disease (CKD) [NICE, 2016; Mantovani, 2018] and CKD can be found in 20–50% of people with MASLD [EASL-EASD-EASO, 2016].
  • The information on alpha-1-antitrypsin deficiency is based on the World Gastroenterology Organisation global guidelines [World Gastroenterology Organisation, 2014] and a regional clinical guideline [Hudson, 2014].

Assessing the risk of advanced liver fibrosis

  • The recommendation to assess the risk of advanced liver fibrosis is based on the NICE guideline that early identification of liver fibrosis is essential for effective management [NICE, 2016]. This is also in line with the EASL clinical practice guidelines which state that identifying fibrosis is the most important prognostic factor in people with MASLD, and is correlated with liver-related outcomes and mortality [EASL-EASD-EASO, 2016].
  • The recommendation to use a first-line, non-invasive scoring system to provide an indirect measure of fibrosis is based on Newsome, The American Association for the Study of Liver Diseases practice guidance, Zhou and the Royal College of General Practitioners recommendations [Newsome, 2018a; Chalasani, 2018; Zhou, 2019; Royal College of General Practitioners, 2021a].
  • The NAFLD Fibrosis Score and FIB-4 Score perform well in comparative studies [Dyson et al, 2014; Sattar et al, 2014]. The American Association for the Study of Liver Diseases concludes that the 'NAFLD Fibrosis Score is a clinically useful tool for identifying NAFLD patients with higher likelihood of having bridging fibrosis and/or cirrhosis' [Chalasani et al, 2012]. NAFLD was the former name for MASLD.
  • The recommendation to consider using the Enhanced Liver Fibrosis (ELF) test to assess the risk of advanced liver fibrosis and liver-related complications in people who need specialist referral is based on the NICE guideline  [NICE, 2016].

Management

Scenario: Management

From age 18 years onwards.

How should I manage MASLD in primary care?

Manage a person with a working diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) in primary care if other causes of liver disease have been excluded, and there is a low risk of advanced liver fibrosis based on the non-invasive testing (NFS, FIB-4 or ELF).

  • Advise the person that there is currently no specific drug treatment licensed for the management of MASLD, but the aim of management is to reduce the risk of progression of MASLD, and to reduce the risks of cardiac and liver-related morbidity and mortality.
  • Give lifestyle modification advice on diet, physical activity, and regular exercise to all people with MASLD, and encourage gradual sustained weight loss, especially if a person is overweight or obese.
    • A recommended target of 5-10% weight loss over 6 months may be helpful with a target calorie deficit of 600kcal/day.
    • EASL recommends a Mediterranean diet which can reduce liver fat even without weight loss.
    • EASL promotes water rather than sugar sweetened beverages.
    • Aim for moderate intensity exercise training for 150-200 minutes per week in 3-5 sessions. Aerobic exercise plus diet is the most effective method of managing MASLD.
    • See the sections on lifestyle advice in the CKS topics on CVD risk assessment and management and Obesity for more information.
  • Advise on drinking alcohol within national recommended limits. Evidence suggests drinking alcohol in the presence of obesity acts synergistically to increase the risk of liver disease morbidity and mortality. See the CKS topic on Alcohol - problem drinking for more information.
  • Ensure that associated conditions such as hypertension, hyperlipidaemia, and type 2 diabetes mellitus are optimally managed. See the CKS topics on Hypertension, Lipid modification - CVD prevention and Diabetes - type 2 for more information.
    • Be aware that people with MASLD do not have any additional risks of hepatotoxicity if prescribed statin drug treatment, and people already taking statins should continue to take them as prescribed. Statin treatment is associated with improvements in steatosis, inflammation and fibrosis.
  • Provide advice on sources of information and support for people with MASLD, such as the British Liver Trust which has a patient guide on Non-alcoholic fatty liver disease. The National Institute for Health and Care Excellence (NICE, available at www.nice.org.uk) also provides a patient information leaflet on Non-alcoholic fatty liver disease (NAFLD): assessment and management.

NICE and EASL guidelines state pioglitazone may be used off-label (in the absence of type 2 diabetes mellitus) in metabolic dysfunction-associated steatohepatitis (MASH). NICE suggest Vitamin E supplementation for non-diabetic patients with MASH. They should be prescribed by secondary care. When consenting patients they should be made aware of the possible increase of 2-4% body weight (after 6-36 months of treatment) and the increased risk of bladder cancer and osteoporosis (in women).

Basis for recommendation

The recommendations on how to manage a person with suspected metabolic dysfunction-associated steatotic liver disease (MASLD) in primary care are based on the National Institute for Health and Care Excellence (NICE) clinical guideline Non-alcoholic fatty liver disease: assessment and management [NICE, 2016], guidance from the American Association for the Study of Liver Diseases[Chalasani, 2018] and European Association of the Study of the Liver (EASL) publication - EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease [EASL-EASD-EASO, 2016] and EASL Policy statement on food, obesity and non-alcoholic fatty liver disease [EASL, 2019]. In addition there are several systematic reviews [Katsagoni, 2017; Zou, 2018; Parra-Vargas, 2020; Komolafe, 2021; Gosal, 2021; Mantovani, 2021].

Weight loss and exercise advice
  • The recommendations on weight loss are based on the NICE guideline which states that there is some evidence that exercise reduces liver fat content, and weight loss achieved as part of a lifestyle modification strategy in adults with MASLD appears to reduce the risk of MASLD progression [NICE, 2016].
    • The benefits of lifestyle modification for the minority of people with MASLD who are not overweight or obese are likely to be smaller [NICE, 2016].
  • According to Zou, Katsagoni diet with aerobic exercise is the most effective intervention. Diet alone improves aminotransferases whereas exercise alone improves insulin sensitivity and BMI[Katsagoni, 2017; Zou, 2018]
  • Mantovani showed that weight loss of at least 10% can produce MASH resolution but more modest reductions will benefit various components of the fibrosis score [Mantovani, 2021] .
Advice on alcohol
  • The advice on drinking alcohol within national recommended limits is based on the NICE guideline [NICE, 2016].
  • Data from two large prospective UK cohort studies showed the effect of drinking alcohol in an obese population[Hart, 2010].
  • The EASL clinical guideline found no evidence to currently recommend abstinence from alcohol for people with MASLD, and states drinking alcohol in moderation 'might even be protective against MASLD, MASH and fibrosis as compared with total abstinence' [EASL-EASD-EASO, 2016].
Managing associated conditions
  • The recommendations on managing metabolic risk factors and associated conditions are widely cited in the literature, and it has been noted that the risk of metabolic dysfunction-associated steatohepatitis (MASH) increases with the number of metabolic risk factors a person has [Dyson et al, 2014]. The NICE guideline also notes that people who are overweight or obese, or have type 2 diabetes, are at increased risk of progressive disease [NICE, 2016].
  • Statin safety in MASLD is discussed in a 2021 systematic review and meta-analysis [Pastori, 2021]

When should I refer a person with MASLD?

 

  • Refer people with suspected or confirmed metabolic dysfunction-associated steatotic liver disease (MASLD) to a hepatology specialist for further assessment and management, if:
    • The person is at high risk of advanced liver fibrosis.
    • There are signs of advanced liver disease on examination.
    • There is uncertainty about the diagnosis.

Specialist investigations and management

Specialist investigations may include:

  • Transient elastography (fibroscan)
    • Fibrotic livers have reduced elasticity, and transient elastography is a non-invasive test which measures liver stiffness, which correlates with the degree of liver fibrosis.
  • Liver biopsy
    • Liver biopsy may be needed to confirm the diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) or cirrhosis, exclude other liver disease, and decide on the need for further management and monitoring in secondary care. It also may be needed where non-invasive tests for the evaluation of liver disease severity suggest advanced fibrosis, or indeterminate or discordant results.
    • It can assess the degree of hepatic steatosis, hepatocellular injury, inflammation, and fibrosis, and provides both diagnostic and prognostic information on liver fibrosis and the potential for progression.
    • It is an expensive and invasive procedure with a risk of morbidity and rarely mortality, with the potential for sampling errors, and is dependent on the interpretation of histopathology results.

Specialist management may include:

  • Monitoring of people with advanced liver disease
    • Surveillance programmes to monitor for hepatocellular cancer (HCC), for example using ultrasound scans and alpha-fetoprotein serum monitoring.
  • Drug treatments
    • In secondary or tertiary care, pioglitazone or vitamin E drug treatment may be considered (off-label indication) for adults with advanced liver fibrosis.
    • There is evidence that obeticholic acid (a synthetically modified analogue of chenodeoxycholic acid) improves the histological features of MASH, including fibrosis.
  • Bariatric surgery results in biopsy confirmed resolution of steatosis in 66% of patients and of fibrosis in 40% patients.
  • Liver transplantation
    • Epidemiology shows MASH will soon become the most common indication for liver transplantation in the US.
    • Outcomes are comparable to transplants for other indications and linked particularly to age, obesity, and presence of T2DM.
    • MASH may recur after liver transplantation. 

Basis for recommendation

The recommendations on when to refer a person with metabolic dysfunction-associated steatotic liver disease (MASLD) are based on the National Institute for Health and Care Excellence (NICE) clinical guideline Non-alcoholic fatty liver disease (NAFLD): assessment and management [NICE, 2016], the European Association for the Study of the Liver EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease [EASL-EASD-EASO, 2016], British Liver Trust and Royal College of General Practitioners recommendations [British Liver Trust & RCGP, 2016] and Clinical practice guidelines from the American Association for the study of liver diseases [Chalasani, 2018]. 

  • The EASL and NICE clinical guidelines highlight that the specialist treatment of metabolic dysfunction-associated steatohepatitis (MASH) should reduce the risk of progression to liver fibrosis and advanced liver disease [EASL-EASD-EASO, 2016; NICE, 2016].
  • Fibroscan was evaluated in a NICE Medtech Innovation briefing [NICE, 2020] This device is already used extensively in secondary care but a smaller version of the device could be used in primary care. The cost per device is £30-70,000 per unit, excluding VAT.
  • Bariatric surgery and its effect on metabolic syndrome and the histological features of MASLD and fibrosis, are documented in a 2019 meta-analysis and systematic review of 32 cohort studies of histological specimens [Lee, 2019] Bariatric surgery resulted in biopsy confirmed resolution of steatosis in 66% of patients. Bariatric surgery and future directions for treatments is also discussed in[Roeb, 2020]
  • Evidence for medications used in secondary care is discussed in[Sawangjit, 2016; Mantovani, 2021].

How should I follow up a person with MASLD in primary care?

Ensure a person with metabolic dysfunction-associated steatotic liver disease (MASLD) and a low risk of advanced liver fibrosis is reviewed in primary care annually, depending on clinical judgement.

  • Examine the person to check:
    • For signs of advanced liver disease, that may indicate progression of MASLD.
    • Blood pressure to assess for hypertension. See the CKS topic on Hypertension for more information.
    • Weight and body mass index (BMI) — to assess for obesity and the impact of any diet and exercise changes on weight loss. See the CKS topic on Obesity for more information.
  • Arrange blood tests to assess for metabolic risk factors, and manage accordingly.
    • Renal function tests to assess for chronic kidney disease. See the CKS topic on Chronic kidney disease for more information.
    • HbA1c to assess for impaired glucose regulation and type 2 diabetes. See the CKS topic on Diabetes - type 2 for more information.
    • Lipid profile — to assess for hyperlipidaemia. See the CKS topic on Lipid modification - CVD prevention for more information.
  • Reassess the person's risk of cardiovascular disease annually — see the CKS topic on CVD risk assessment and management for more information.
  • Reassess the person's risk of advanced liver fibrosis every 3 years — do not use routine liver blood tests. See the section on Assessment for more information.
    • If the person is at high risk of advanced liver fibrosis, refer the person to a hepatology specialist for further assessment and management.
    • If the person is at low risk of advanced liver fibrosis, reassess the risk every 3 years, and continue to manage the person in primary care.

Basis for recommendation

The recommendations on follow up of a person with metabolic dysfunction-associated steatotic liver disease (MASLD) in primary care are based on the National Institute for Health and Care Excellence (NICE) clinical guideline Non-alcoholic fatty liver disease (NAFLD): assessment and management [NICE, 2016], the European Association for the Study of the Liver EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease [EASL-EASD-EASO, 2016], and the British Liver Trust/Royal College of General Practitioners article on Non-alcohol-related fatty liver disease and its primary care management [British Liver Trust & RCGP, 2016] and the Practice guidance from the American Association for the study of liver diseases [Chalasani, 2018].

Frequency of primary care review
  • The recommendation that all people with MASLD should be reviewed in primary care annually is pragmatic, based on what CKS considers to be good medical practice, as people with MASLD are likely to have additional risk factors for developing cardiovascular disease and metabolic syndrome.
Assessing for metabolic risk factors
  • The recommendation on reassessing metabolic risk factors at review is based on the EASL and NICE clinical guidelines, that a worsening metabolic risk factor profile may increase a person's risk of developing metabolic dysfunction-associated steatohepatitis (MASH) [EASL-EASD-EASO, 2016; NICE, 2016]. Specifically, people with type 2 diabetes are at increased risk of more progressive fibrosis in MASH, so it is important that people with MASLD are regularly screened for diabetes mellitus  [NICE, 2016].
Reassessing risk of cardiovascular disease
  • The importance of reassessing cardiovascular risk is highlighted in the NICE guideline [NICE, 2016] and in a regional clinical guideline that states that people with MASLD are more at risk of cardiovascular morbidity and mortality than liver-related complications [Hudson, 2014].
Reassessing risk of advanced liver fibrosis
  • The recommendation on reassessing the risk of advanced liver fibrosis every 3 years for people with a low risk of advanced liver fibrosis is based on expert opinion in the NICE guideline [NICE, 2016].
    • NICE found that a shorter frequency for rechecking the risk of advanced liver fibrosis was not cost-effective, even if the person has additional risk factors for progressive liver disease [NICE, 2016].
    • NICE recommends against using routine liver blood tests to assess for advanced liver fibrosis. In addition, the World Gastroenterology Organisation highlights that liver function tests (LFTs) may be unreliable in monitoring MASLD disease progression to MASH. It states that MASH is often under-diagnosed as progressive fibrosis may be present with stable or improving LFT results [World Gastroenterology Organisation, 2012].

Supporting evidence

This CKS topic is based on the National Institute for Health and Care Excellence (NICE) clinical guideline Non-alcoholic fatty liver disease (NAFLD): assessment and management [NICE, 2016], The British Liver Trust and RCGP recommendations[British Liver Trust & RCGP, 2016] and EASL Policy document on food, obesity and NAFLD [EASL, 2019] and American practice guidelines[Chalasani, 2018], together with many international systematic reviews, meta-analyses and randomised controlled trials. The rationale for the primary care diagnosis, management, and referral of MASLD is discussed in the relevant basis for recommendation sections. CKS only briefly discusses the evidence for secondary care investigations and management such as may be beneficial for general awareness in primary care clinicians.

How this topic was developed

This section briefly describes the processes used in developing and updating this topic. Further details on the full process can be found in the About Us section and on the Clarity Informatics website.

Search strategy

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of non-alcoholic fatty liver disease.

Search dates

September 2016 - August 2021

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

  • non-alcoholic fatty liver disease/
  • (((fatty or fat or steato*) adj3 (liver* or hepat*)) or steatohepat* or (visceral adj2 steato*)).ti,ab
  • "non alcoholic fatty liver".tw,
  • NAFLD or NASH or MAFLD.ti,ab.

Sources of guidelines

Sources of systematic reviews and meta-analyses

  • The Cochrane Library:
    • Systematic reviews
    • Protocols
    • Database of Abstracts of Reviews of Effects
  • Medline (with systematic review filter)
  • EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

Sources of randomized controlled trials

  • The Cochrane Library:
    • Central Register of Controlled Trials
  • Medline (with randomized controlled trial filter)
  • EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Sources of national policy

Patient experiences

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

  • Clinical accuracy.
  • Consistency with other providers of clinical knowledge for primary care.
  • Accuracy of implementation of national guidance (in particular NICE guidelines).
  • Usability.

Principles of the consultation process

  • The process is inclusive and any individual may participate.
  • To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
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  • Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
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  • Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
  • All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
  • All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

  • Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
  • Stakeholders identified from the following groups are invited to review draft topics:
    • Experts in the topic area.
    • Professional organizations and societies (for example, Royal Colleges).
    • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
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Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

  • Topic selection
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  • First draft internal review
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  • Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

  • Animal studies
  • Original research is not written in English

Possible exclusions for reviewed literature:

  • Sample size too small or study underpowered
  • Bias evident or promotional literature
  • Population not relevant
  • Intervention/treatment not relevant
  • Outcomes not relevant
  • Outcomes have no clear evidence of clinical effectiveness
  • Setting not relevant
  • Not relevant to UK
  • Incorrect study type
  • Review article
  • Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

  • Feasibility
    • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
  • Organizational and Financial Impact Analysis
  • Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
    • Eligible population
    • Current interventions
    • Likely uptake of new intervention or recommendation
    • Cost of the current or new intervention mix
    • Impact on other costs
    • Condition-related costs
    • In-direct costs and service impacts
    • Time dependencies
  • Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

  • Personal financial interests
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Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

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Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.

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