nash: diagnosis and management in primary...
TRANSCRIPT
My background
GP and trainer in Redditch
EASL Lancet Commission Chair Primary Care Working Group on Liver Disease in Europe
NICE NAFLD Guideline Group member
Member Lancet UK Commission on Liver Disease
RCGP Clinical Advisor, NICE Fellowship 2015-18
Author Weight Matters for Children Radcliffe Publishing
Founder of Primary Care Obesity Training Ltd
http://primarycareobesitytraining.wordpress.com
And painter…!
NO FINANCIAL DECLARATION OF INTEREST FOR SPEAKING TODAY
Outline: Why GPs know nothing about
NASH… and why this doesn’t matter!
How much LD do GPs see?
Case example - practice audit
Essential LD knowledge for GPs
Understanding different factors
leading to cirrhosis
Facilitating GP engagement in
liver disease
Barriers
Case examples of change
Learning points
“From now on I
operate on a ‘need to
know’ basis –
everything you say is
stuff I don’t need to
know”
GP perceptions of liver disease
Liver disease kills
relatively younger
people – hence its
importance
But, for GPs, LD is
dwarfed by
chronic disease and
frailty,
mental health,
reproductive health
child health
Stigma around risk
factors is common
UK mortality data 2015
Audit of changes in liver disease
coding in a UK practice
Audit of liver disease coding in a UK 8 partner GP practice 2016 and 2019
2016 audit 2019 audit
Practice list size (patients) 16074 17400
Coding of:-
Patients with any recorded liver diagnosis 302 (1.9%) 540 (3.1%)
Patients with LD and recorded alcohol status 54% 95%
Fatty liver 99 349
NAFLD (expected population prevalence 20-30%) 4 (0.01%) 163 (1%)
NASH - but (*coded as steatosis of liver) 0 0 (18*)Cirrhosis 25 48
HCC or primary liver cancer (not known) 3
Hepatitis B or C infection 10 88
Deaths recorded due to liver disease 2 of 103
deaths (2%)
4 of 87 deaths
(4.6%)
Why is fatty liver important to GPs?
Liver-related deaths have
quadrupled in last 30 years whilst
heart disease and stroke have
fallen
Increasing alcohol consumption
and obesity mean risk increasing
Largely avoidable
Relevant to multi-morbidity due to
shared risk factors - One of the
‘Big Five’!
Currently presents late – but long
latent phase indicates opportunity for prevention
Simple fibrosis pathway
Disease progression from fatty infiltration of liver
Metabolic NAFLD
T2DM, metabolic
synd, obesity – fat
deposition
Alcohol ARLD
Fat deposition
and direct
alcohol toxicity
Hepatitis C HCV-induced
steatosis
Fatty infiltration due to Hep C
virus
Process:
Persistent inflammation - reversible scarring and fibrosis
‘Metabolic’ NASH / ASH HCV-induced steatosis
Process:
Ongoing fibrosis - irreversible scarring
Cirrhosis
irreversible shrunken scarred liver architecture
End-stage liver failure Hepatocellular carcinoma
What does this mean for GPs?
Disease progress from fatty infiltration of liver Action
Metabolic NAFLD
T2DM, metabolic
synd, obesity – fat
deposition
Alcohol ARLD
Fat deposition
and direct
alcohol toxicity
Hepatitis C HCV-
induced steatosis
Fatty infiltration due to
Hep C virus
Prevent
Screen
Assess fibrosis*
Advise
CodeProcess:
Persistent inflammation - reversible scarring and fibrosis
‘Metabolic’ NASH / ASH HCV-induced steatosis *Refer
Process: Ongoing fibrosis - irreversible scarring
Cirrhosis
irreversible shrunken scarred liver architecture
*Refer
Code
Follow upEnd-stage liver failure Hepatocellular carcinoma
Teach team members
according to their specific role
Engage GPs in
Vaccination programmes
Early detection e.g. risk based case
finding in high risk groups
Appropriate fibrosis risk assessment
Referral according to locally adopted
pathway
Issue lifestyle advice - repeatedly
Code correctly (to allow audit and
multidisciplinary approaches)
(We don’t need to know about NASH…!)
“Train to the task…”
Keep it simple:
Essential facts
Causes
Incidence
Identifying
Assessing fibrosis risk
Consider wider
metabolic risk – and how
LD aligns with person
centred care
Causes of fatty liver
Alcohol
Obesity
Hepatitis C
High fructose intake from soft drinks
Pregnancy
Drugs (amiodarone, antiviral drugs, steroids, methotrexate, tamoxifen, tetracycline)
Total parenteral nutrition
Genetic conditions
Hepatitis B
Polycystic ovarian syndrome
Stage Incidence Relevance
NAFLD 20- 30% population Benign for majority, but precursor of cirrhosis
NASH (– hepatic
inflammation due to NAFLD)
2-3% population Reversible with lifestyle change
Alcohol-related LD (ARLD)
Caused 1.4% of all deaths
in 2014
63% were from alcoholic liver disease
Under 50% five year
survival for alcoholic
cirrhosis if continue to drink
Cirrhosis Develops in10–20% of
people with NAFLD, ARLD
and chronic viral hepatitisover 10–20 years
Irreversible.
Around 600 people
receive a liver transplant annually in UK
Hepatocellular
carcinoma (HCC)
3-4% of people with
cirrhosis will develop HCC per year
Without surveillance,
outcome typically poor (months)
Incidence
(WC, Gamma GT,
triglycerides)*Not sufficient evident for this to be NICE NAFLD recommendation
Should GPs
screen for
NAFLD?
Liver disease is typically an incidental finding
70–80% of subjects with central obesity and 50–80% of patients with type 2 diabetes have evidence of NAFLD on imaging
Risk-factor case finding is feasible – e.g Scarred Liver Project https://www.scarredliverproject.org.uk/#top
Fatty Liver Index -FLI algorithm predicts risk of NAFLD but evidence for screening was insufficient to recommend screening
FLI - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1636651/
Identifying NAFLD - adults
Diagnosis of exclusion – TAKE ALCOHOL HISTORY and
consider other causes of liver disease
LFTs are not diagnostic – may be normal or raised at any
stage of liver disease. Look at trends
Case finding:
Index of suspicion in high risk groups due to insulin
resistance risk factors
Incidental finding of fatty liver on ultrasound for other
reasons
Finding of fatty liver during investigation of persistently
raised LFT
UK NICE: Assess risk of
fibrosis for NALFD patients
Assess fibrosis risk using ELF
blood test – Enhanced
Liver Fibrosis test – 3
biomarkers
Refer hepatologist if ELF
score is 10.51 or above -
confirming fibrosis.
Reassure benign pattern if
ELF under 10.51 but
repeat ELF every 3 years
Alternative algorithms or
imaging options to assess
fibrosis risk :
Algorithms
APRI – AST/Platelet Ratio Index – algorithm
NAFLD fibrosis score –algorithm (age, BMI, DM, AST, ALT, platelets, albumin)
FIB-4 –algorithm (age, platelets, AST and ALT)
Scanning
Transient Elastography – modified USS measuring liver stiffness
ARFI - acoustic radiation force impulse – alternative USS test for liver stiffness
NAFLD : hepatic expression of
metabolic syndrome
NAFLD is a risk factor for
type 2 diabetes
hypertension
chronic kidney disease
In T2diabetics, NAFLD is a risk factor for
atrial fibrillation
myocardial infarction
ischaemic stroke
death from cardiovascular causes
“According to the
computer, I need
to back up your
kidneys, defrag
your liver and
reboot your heart”
Statins and NAFLD - reassure
Highest mortality for people with
NAFLD will be from
cardiovascular disease
People with NAFLD who are
taking statins should keep taking
them, bearing in mind NAFLD’s link to metabolic syndrome.
Only consider stopping statins if
liver enzyme levels double within
3 months of starting statins,
including in people with
abnormal baseline liver blood results.
Treatment
There are no medical treatments
for NAFLD
Lifestyle improvements to
increase physical activity and
lower BMI can reduce liver fat
content and influence
outcomes.
Remind people to stay within the
national recommended limits for
alcohol consumption.
Evidence does not currently
support recommending abstinence from alcohol for
people with NAFLD
Conveying obesity and
lifestyle advice
Avoid frightening patients. Fear is a
poor motivator and may trigger denial or resistance
Explore patient-generated goals –
rather than health professional
ideals
Use direct (rather than indirect)
measures to assess success in order
to produce a virtuous motivational
circle
Signpost to local lifestyle services
and bariatric pathway
“Our challenge is to
convince the public
that heart attacks
are sexy.”
Direct and indirect gains from
weight loss
Direct gains – clear link to
weight loss
Confidence
Looking good
Self-esteem - feeling happy
More energy
Improved breathing
Less aches and pains
Reduced gallstone pain
Improved constipation/IBS
Indirect gains – no visible
link to weight loss
Life expectancy
Lower cholesterol
Reduced disease risk –
(diabetes, stroke, CVD,
cancer, OA, dental caries,
depression)
Improved lung function
Improved fatty liver
Increased fertility
Direct personal gain
Tangible to individual but least
benefit to health care system
Indirect personal gain
Benefit to population but
imperceptible to individual
GP action if NASH or
Cirrhosis
If a patient has raised ELF (or APRI etc) refer to local pathway or hepatology team for fibrosis imaging (eg
transient elastography or ARFI)
Ensure condition is coded to enable appropriate review
Invite for annual review – keep register
Screen for other metabolic conditions
At annual review ensure hepatologist review is in place
Continue statin unless liver function is 3 times higher than
baseline
Case examples
ADDRESSING BARRIERS FOR
GPS
Policy changes are most impactful:
Liver cirrhosis death rates in Scotland
Acknowledgements Scottish Public Health Observatory accessed November 2019https://www.scotpho.org.uk/health-wellbeing-and-disease/chronic-liver-disease/data/mortality
Scotland has
developed policy
measures on
alcohol, hepatitis
and obesity.
Policy aims to
‘change
Scotland’s
relationship with
alcohol’ -
Minimum Unit
Pricing of alcohol
began May 2018
Simplify and unify Liver Fibrosis
testing: Traffic light coding
In addition to lack of consensus over which fibrosis tests to use, there is no unity for high risk cut-off values
Cut-off values for FIB-4 index, APRI and eLIFTscores were 3.25, 1, and 8, respectively.
NAFLD fibrosis score’s arbitrary scale uses below -1.455 to exclude advanced fibrosis and above 0.675 to indicate high likelihood of fibrosis. Values between these are indeterminate. Interpreting negative numbers to several decimal points is confusing and off-putting.
All tests could be rescaled to create a simple intuitive scoring system or traffic light coding
“For me to use any
scoring system, it must
be simple and
intuitive. Expecting
me to interpret a set
of figures that involves
minus numbers to 3
decimal points is just
unrealistic.”
Dr S Oliver, GP W Midlands, UK
Formula to rescale NFS to 0 to 10
Range of
NALFD Score:
Rescaled to: New range Traffic Light
Action
𝑥 < −3 0.5𝑒2.5𝑥+7.5 0 − 0.5 Advanced
fibrosis excluded
Reassure, lifestyle
advice
−3 ≤ 𝑥< −1.455
1.618𝑥 + 5.344 0 .5 − 2.9
−1.455 ≤ 𝑥< 0.675
1.878𝑥 + 5.732 3 − 6.9 Indeterminate:
refer
0.675 ≤ 𝑥 < 2 1.887𝑥 + 5.726 7 − 9.5 High risk
advanced
fibrosis: refer2 ≤ 𝑥 10 − 0.5𝑒5−2.5𝑥 9.5 − 10
An editable spreadsheet using this formula is available at:
https://docs.google.com/spreadsheets/d/1DWDewqzcNWHQMO24
OXm-HvTC75y2VnBB5IGW9Z5vdo8/edit?usp=sharing
Formula by Alistair Pryke BA (Camb)
Pathways into
Practice https://www.scarredliverproject.org.uk/#top
Used an algorithm-based pathway to detect earlier cirrhosis, involving GP risk factor-based case finding then community transient elastography.
Aligning lifestyle intervention with diagnostic assessment provides a relevant conversation opportunity, particularly for people with related co-morbidities, such as diabetes and CVD
Funding issues affect capacity – waiting times for TE have increased
‘Disease silo thinking’ and challenges in pinpointing hard outcomes, in view of the long lead time for cirrhosis, have affected commissioner willingness to invest more.
“General Practitioners also noted a striking
number of patients finally engaging in important lifestyle changes following
pathway implementation.”
Take home messages
GPs are interested but not confident in LD . https://www.rcgp.org.uk/-/media/Files/CIRC/Liver-Disease-Toolkit/GP-survey--SL.ashx?la=en
GPs don’t need detailed knowledge of NASH to
support improved care
Focus LD training for GPs on essential primary care roles:
Vaccination programmes
Early detection, fibrosis risk assessment and referral pathways
Issue patient-centred lifestyle advice - repeatedly
Code correctly
Simplify test results – make it easy for non-specialist GPs
References and relevant
NICE guidelines
NICE. Non-alcoholic fatty liver disease (NAFLD): assessment and management. NG49. July 2016. https://www.nice.org.uk/guidance/ng49
BSG Guidelines on the management of abnormal liver blood tests https://gut.bmj.com/content/67/1/6
NICE. Cirrhosis in over 16s: assessment and management. NG50. July 2016. https://www.nice.org.uk/guidance/ng50
NICE Obesity pathway https://pathways.nice.org.uk/pathways/obesity
Williams R, Aspinall R, Bellis M et al. Lancet Commission: Addressing liver disease in the UK: Lancet 2014; 384:1953-97. http://www.thelancet.com/commissions/crisis-of-liver-disease-in-the-UK