Non Alcoholic Fatty Liver Disease (NAFLD) - Adult Leeds

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1.  Background Information

Quick info:

This pathway has been developed with the Department of Hepatology at St. James's University Hospital (Drs Rebecca Jones and Lee Claridge) and the Leeds pan-city Liver Collaboration with the Leeds CCGs, University of Leeds and Leeds City Council (Public Health). A formal evaluation project is running alongside its publication.

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2.  Information for Patients and Carers

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The British Liver Trust has an excellent patient information leaflet on NAFLD - www.britishlivertrust.org.uk/liver-information/liver-conditions/non-alcohol-related-fatty-liver-disease/

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3.  Updates to this Care Map

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Date of publication: March 2015

The content of this pathway has been agreed and approved by the Dept of Hepatology (LTHT) and the Leeds CCGs.

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4.  Non Alcoholic Fatty Liver Disease (NAFLD) - Suspected

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NAFLD is one of the commonest causes of chronic liver disease in the UK. The spectrum of disease ranges from simple fat (steatosis) through to fat plus inflammation (Non-alcoholic steatohepatitis or NASH) with various stages of fibrosis, through to Cirrhosis. Based on our current knowledge most patients will have low risk of developing significant liver related disease and can be either managed in primary care along, or in low intensity secondary care follow-up.

Patients with NAFLD, and especially those with NASH, have a high risk of morbidity and mortality from cardiovascular disease, and any management must address treatable risk factors and primary prevention interventions for this.

The typical patient with NAFLD will be overweight, if not obese, and have one or more manifestations of the metabolic syndrome:

type 2 diabetes or pre-diabetes, hypertension or dyslipidaemia. Hypertriglyceridaemia is especially recognised.

By definition, alcohol has been excluded as a significant co-factor. This can be difficult and excess alcohol and the metabolic syndrome are of course not mutually exclusive and often coexist. GPs need to be careful with taking an accurate alcohol history. Alcohol plus obesity together act in synergy to increase the risk of significant liver disease, and when taken in excess alcohol intake must be addressed as an essential part of management.

Patients may have normal liver function tests, even with significant liver damage; or may have had an ultrasound which shows a fatty liver - other terms used in the report might refer to the liver as "bright" or "echogenic." Where liver function tests are abnormal, it is most usually as an isolated rise in ALT and most usually < x 3 the upper limit of normal. Often GPs will find that the abnormality has been seen before perhaps as part of diabetes, statin or CVD monitoring.

Other causes of liver disease which require specific treatments or different management approaches should be excluded. The relevant tests for other chronic liver diseases are explained in the abnormal isolated ALT pathway. A small proportion of patients with NAFLD will have a positive yield from one of these tests e.g. a raised ferritin or a positive immunology screen. In such cases, although the patient phenotype fits the typical presentation it is not possible to be confident of the diagnosis in primary care, and we advise referring for a specialist review where consideration will be given to a liver biopsy.

Because patients with advanced liver disease are often asymptomatic until the liver starts to fail, other surrogate markers in this context which might point to a significant fibrosis or cirrhosis include splenomegaly on ultrasound, thrombocytopenia on a full blood count or a reduced albumin. All these should act as "alarm signs" and trigger referral for specialist opinion.

Aetiology Screening Tests:

(a) Ultrasound of liver and upper abdomen

(b) Hepatitis B serology results - NB if positive please refer as hepatitis B

© Hepatitis C serology results - NB if positive please see hepatitis C referral guidance

(d) Liver auto antibodies (Anti-nuclear antibody, anti smooth muscle antibody, anti mitochondrial antibody, anti LKM antibody)

€ Immunoglobulins (IgA, IgM and IgG)

(f) Coeliac serology

(g) Thyroid function tests

(h) Serum ferritin

(i) Alpha-1-antitrypsin level

(j) If patient is ≤ 50 years of age then a serum caeruloplasmin is required

(k) HbA1c

(l) Liver function tests

(m) Full blood count

(n) Lipids

(o) AST (request AST:ALT ratio)

(p) BMI

Features allowing confident diagnosis of NAFLD in Primary Care

  • ALT Normal-x3ULN
  • BMI >28
  • BMI <28 plus any metabolic syndrome history
  • Negative aetiology screen
  • Fatty liver on USS
  • Asymptomatic and otherwise well patient

GP Diagnosis: Not Confident

  • ALT >x3ULN
  • BMI <28, no other metabolic syndrome history
  • Normal USS
  • ALP rise only abnormality, even with features
  • Any positivity on aetiology screen
  • Symptomatic patient
  • Hepatomegaly
  • Thrombocytopaenia, low albumin, raised bilirubin, splenomegaly on USS

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5.  Confident of NAFLD Diagnosis

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GP Diagnosis: Confident

  • ALT N-x3ULN
  • BMI >28
  • BMI<28 plus any metabolic syndrome history
  • Negative aetiology screen
  • Fatty liver on USS
  • Asymptomatic and otherwise well patient

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6.  Not Confident of NAFLD Diagnosis Refer Hepatology

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GP Diagnosis: Not confident

  • ALT >x3ULN
  • BMI <28, no other metabolic syndrome history
  • Normal USS
  • ALP rise only abnormality, even with features
  • Any positivity on aetiology screen
  • Symptomatic patient
  • Hepatomegaly
  • Thrombocytopaenia, low albumin, raised bilirubin, splenomegaly on USS

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7.  Risk Score Patient if Happy to Do So

Quick info:

This pathway uses 2 non-invasive scores for risk stratification into a group that have a low risk of fibrosis. BARD scores of <2 are reported to have a high negative predictive value for fibrosis; as are NAFLD scores of < -1.455. They have not yet been well validated in primary care settings so this pathway requires both criteria to be met for management in primary care without further evaluation.

We use HBA1c to define diabetes and pre-diabetes for the NAFLD score. The original papers used the HOMA index, which is not widely used. We have taken a pragmatic view on this.

BARD score

Diabetes = 1 point

AST:ALT ratio  ≥ 0.8 = 2 points

BMI ≥ 28 = 1 point

NAFLD Fibrosis Score

Components are Age (yrs), BMI, Impaired fasting glucose/diabetes, AST, ALT, Platelets and Albumin. The calculator is found at this website:

http://nafldscore.com/

NB - you must clear it each time or you will use previous details.

Be aware the calculated figure is a MINUS figure - the cut off is -1.455. Higher than this (e.g. -1.3) requires referral, lower (e.g. -1.6) is OK for primary care management as long as BARD score is <2.

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8.  If Not Happy To Risk Score Refer Hepatology

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If you think your patient has NAFLD but are either not confident with making the diagnosis yet, or with risk stratification please refer to Hepatology.

Please ensure all the investigations are done ahead of referral, and let us know whether you think NAFLD is the diagnosis. Your patient will be assessed in a clinic that is run by experienced hepatologists and similar principles within the pathway will follow. If NAFLD is confirmed as the working diagnosis and your patient is low risk stratified, a nurse-delivered telephone consultation will be given, and a copy of the personalised plan will be sent to both you and your patient. You should then follow the advice in boxes 'Bard score <2 and/or NAFLD score <-1.455' and 'Alcohol Advice,' 'CVD risk assessment & management' and 'Weight Management'. A 5 year follow-up appointment in the fatty liver clinic will follow.

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9.  Bard Score <2 and NAFLD Fibrosis Score <1.455

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Patients can be told that they have fatty liver disease and an explanation can be given that it is most probably related to their weight or diabetes (as applicable) or both. They can be reassured that their liver does not appear to be significantly damaged at present, but that lifestyle changes need reviewing to reduce the risk of it changing in the future. These are also necessary because of the increased risk of cardiovascular disease in the future, and also of diabetes, (NAFLD is thought to be the hepatic manifestation of the metabolic syndrome.)

Explain to patients that they should not consider that because they feel well they are not at risk of things changing in the future, as liver problems rarely cause any symptoms until very advanced when the liver may fail or develop cancer.

The British Liver Trust has an excellent patient information leaflet on NAFLD - http://www.britishlivertrust.org.uk/liver-information/liver-conditions/non-alcohol-related-fatty-liver-disease/

For alcohol advice, weight management and cardiovascular disease risk management in NAFLD see the boxes below. In summary, the management plan should include:

  • Target exercise of 30 mins/day or 150 mins/week with examples that might suit your patient. This has been shown to reduce hepatic fat, and of course has other benefits too. There might be multiple low cost facilities such as council run swimming pools, gyms and exercise classes that might be useful. Try to agree a personalised exercise plan with your patient.
  • Target weight loss plan of 10% weight reduction over 6 month period
  • Brief intervention on alcohol intake
  • Brief intervention to stop smoking

We recommend a formal review in primary care at 3 months to assess progress against a personalised lifestyle management plan, and thereafter annually unless the GP or patient feels would benefit from more frequent visits.

At the annual review we recommend cardiovascular risk stratification - testing for diabetes, hypertension, dyslipidaemia, checking weight and BMI and reviewing exercise plan. There is little benefit in repeating the ALT - it is likely to fluctuate.

At 5 years we recommend a liver health check:

  • Ensure no new risk factor for an additional liver disease - this would most usually apply to a viral hepatitis risk.
  • Check no new thrombocytopaenia on full blood count and that the albumin remains normal.
  • Repeat the BARD and NAFLD fibrosis scores. If there has been a change from low risk, please refer to Hepatology. If all is stable, then no further liver health check is routinely indicated.
  • If the cardiovascular risk factors persist and/or lifestyle changes have not been made GPs may wish to continue with an annual check up. However, if risk factors are low and lifestyle changes have been positive and sustained it seems reasonable to stop regular review at that point.

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10. Bard Score ≥ 2 and/or NAFLD Fibrosis Score ≥ 1.455

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At these cut-offs fibrosis or more advanced disease cannot be excluded with a good predictive level.

These patients should be referred to Hepatology for further evaluation.

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11. Alcohol Advice

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There is no known safe alcohol limit for patients with NAFLD. Even those not fulfilling the low risk criteria but without severe fibrosis a very small amount of up to 4 units per week may actually be beneficial for the cardiovascular disease risk. For patients with low predictive risk stratification scores we think a modest amount of alcohol can be permitted.

Tools such as AUDIT C can be very useful, however there is a skill to asking the questions and it can be useful to probe a little deeper. Knowledge regarding what constitutes a unit is recognised to be highly variable - even amongst healthcare professionals! Our recommendation for this group is to advise on reduced "recommended" limits to half:

  • 10 units/week for men
  • 7 units/week for women

Advise on avoidance of bingeing and importance of 2-3 alcohol free days/week to prevent habitual drinking. Also emphasise the calorific content of alcohol, often not appreciated, and the sugar content of many alcoholic drinks which add to the risk of future insulin resistance.

On the other side of this pathway patients with some steatohepatitis but without advanced scarring will be advised to reduce alcohol intake to a maximum of 4 units per week. Those with advanced fibrosis or cirrhosis will be advised to stop alcohol intake.

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12. CVD Risk Assessment & Management

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Use the Q-Risk tool for cardiovascular risk assessment. Usual cardiovascular risk management principles apply.

We recommend an annual review for CVD risk assessment, in patients not already undergoing this for diabetes management. Checks for diabetes, hypertension and dyslipidaemia are suggested. The onset of each can be managed along standard primary care guidelines.

Statins are generally safe to use. Hepatotoxicity is rare, and idiosyncratic in nature. The ALT may change slightly when first started. This is common. Remember that the ALT frequency fluctuates in NAFLD disease patients anyway. Only if it rises >x3 ULN or baseline or the patient becomes jaundiced should it be discontinued. The Yorkshire and Humber Liver Network have guidance which should be helpful.

Because the risk of CVD is increased in patients with NAFLD, smoking should be strongly discouraged. Nicotine replacement products are safe to use in patients with NAFLD. Any reactions are idiosyncratic.

Target exercise of 30 mins/day or 150 mins/week with examples that may suit your patient. This has been shown to reduce hepatic fat, and of course has other cardiovascular benefits too.

Target weight loss plan of 10% weight reduction over 6 months period benefits NAFLD and cardiovascular disease risk in overweight patients, especially in the obese category. Your practice may have access to exercise prescribing, which could be used at your discretion.

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13. Weight Management

Quick info:

Target weight loss plan of 10% weight reduction over 6 months period benefits NAFLD and cardiovascular disease risk in overweight patients, especially in the obese category.

Use the Eatwell Plate as a visual guide to assist education around healthy eating, food-type proportions and portion size. Recognised weight loss third sector organisations such as Weight Watchers and Slimming World are safe in this low risk group. In general we advise against food exclusion diets. There is no strong evidence for this advice, though the long term plan is for overall changes to lifestyle and weight in the long term, so the emphasis must be on sustaining changes once achieved.

Medication aids such as Orlistat are probably safe in this low-risk stratified patient group.

Refer to Leeds Weight Management services as per guidelines for referral.

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14. Refer Hepatology

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At these cut-offs fibrosis or more advanced disease cannot be excluded with a good predictive level. These patients should be referred to Hepatology for further evaluation.

The second part of this pathway involves an initial consultation with an experienced hepatologist, and the use of 2 further specialised non-invasive assessments. A follow-up appointment in the fatty liver clinic will follow for results and on-going evaluation. A liver dietician and direct weight management service referrals are available in this clinic also. The pathway is designed to further risk stratify to maintain a low frequency hospital follow-up schedule. The basic principles as outlined in the low-risk boxes apply to the primary care co-management for GPs guidance. A liver biopsy may be necessary as part of the evaluation, but not always. It is reserved for those where either one of 2 further tests cannot subdivide into low risk or advanced confidently, thus eliminating the need for biopsy in many patients. Recommendations about liver biopsy will be made on individual patient basis, as some will have limited long term benefit from staging or will have contra-indications to biopsy.

Key Dates

Published: 19-Mar-2015, by Leeds
Valid until: 01-Mar-2017

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