1. The Nottingham liver disease stratification pathway
Dr Neil Guha and Dr Emilie Wilkes
11/08/2019

2. Outline of session LFTS in primary care
Why the need for change and aims of the pathway
Walk through the pathway using examples

3. LFTs in primary care LFTS are utilised widely in primary care
Ballets study table
>40 % chronic disease
Management

4. Three perspectives What we currently do with abnormal LFTS
Primary care
Ignore as not requested for liver (anxiety)
Repeat (might go away)
Refer to secondary care (expense and futility)
Patient
Is my liver damaged, why and what can be done?
Abnormal Liver tests = alcohol
Secondary care
Non-significant disease in new referrals.
LFTS unhelpful in identifying patients
at high risk of liver mortality (e.g. cirrhosis)
End stage liver disease presenting as an emergency (50 % of cirrhosis on index admission associated with 17 % mortality rate)

5. The rationale for detecting significant liver disease
Patient perspective
Have I got something seriously wrong with my liver now?
Will I die from this, if so when and from what ?
Are things getting worse or better with or treatment/observation ?
Healthcare perspective
Can we pick this up at a stage where it is serious enough to intervene but not too late to be palliative and/or expensive
Can we intervene with liver specific interventions ( e.g. Pioglitazone in NAFLD and cirrhosis strategies)
Can we organise care in an effective manner (outcomes and costs)
Can we “nudge” behaviour in a positive way for lifestyle aetiologies
Can we select appropriate patients for emerging and/or expensive treatments

6. How do we assess liver disease

7. Natural History of Chronic Liver Disease
Risk Factors
Alcohol
Obesity / Diabetes
Viral hepatitis
Scarring
Severe Scarring (Cirrhosis)
Symptoms
Death
Not all individuals are suse
5-20 yrs %/yr

8. A pilot study to tests a community pathway
Targeting risk factors
Synergistic in effect
Applicable to multiple aetiology
Diagnostics performed in the community
Point of care diagnostics in primary care
Diagnostics/brief intervention delivered by nurses
Specialists placed in the community
Integrated primary and secondary care
Hepatology clinics in primary care
Number of fundamental changes to usual care when we initiated our novel investigation pathway:
Targeting investigations on risk factors for liver disease (namely hazardous alcohol use and type 2 diabetes) rather than abnormal LFTs alone.
Improvement of the primary care-secondary care interface – trained nurses performing a Fibroscan in the community setting (Fibroscan (TE) is an ultrasound-based investigation detecting liver stiffness), but also hepatologist review in the community for those with abnormal Fibroscan results.
Evidence from the smoking cessation literature that numerical biomarker feedback improves smoking cessation rates; reason to believe the same would be true of Fibroscan.
McCorry et al., QIM 2012;
Dolman et al., Liv Int 2013

9. Fibroscan Measures a cylinder of liver tissue 100x greater than biopsy
Metaanalyses – positive and negative predictive values for cirrhosis of >95%

10. Fibroscan Results affected by:
Obesity
Narrow Rib spaces
Liver inflammation
May not be possible to obtain reliable reading
Operator dependent
Contraindicated in pregnancy, intracardiac devices
Metaanalysis – >90% NPV and PPV for cirrhosis
Friedrich-Rust et al, Gastroenterology, 2008
Main established cut off = 8kpa – majority of normal patients fall under this threshold
Community based liver study
Obesity – distance to liver capsule
Narrow rib spaces (prob won’t fit)
Liver inflammation – also increases speed of vibration wave
(contraindicated in

11. Outcomes Liver disease
Increased detection of significant liver disease (25 % of those having a community scan) including cirrhosis (3 fold increase)
68.3% of patients with elevated liver stiffness had normal liver function enzymes
73.1% of patients with proven cirrhosis had normal liver function enzymes
Patient experience (n=349; 378 forms distributed)
93.7% of patients would definitely recommend service to friends and family
95.9% felt that the appointment was important or very important for their health
94.3% felt they were given enough information
Engagement with pathway
95 % of investigations were performed in the community setting
Attendance rate for community Fibroscan appointment was 95 %
Cost effective
ICER for NAFLD and ALD are £2,000 and £6,000 respectively

12. Changing our Approach to Liver Disease
Current approach:
Lacks accuracy
Late detection
Hospital based
Costly and invasive
Alternative approach:
Focus on risk factors
Early detection
Community testing
Cost saving
NHS innovations award winners 2013
BMJ team of the year finalists 2015

13. NICE guidelines 2016 on NAFLD and cirrhosis
Awareness that NAFLD is common in type 2 diabetes/met syndrome
Detection of NAFLD. FLI index was most cost effective – not a definitive recommendation
Detection of advanced fibrosis in NAFLD ( serum markers of liver fibrosis – ELF score)
Confirmation of cirrhosis using Fibroscan ( hazardous alcohol and advanced fibrosis in NAFLD)
Statins should not be stopped (unless liver enzymes double within 3/12)
Pioglitazone recommended for advanced fibrosis in NAFLD
Cirrhosis surveillance recommended for varices (OGD) and HCC (U/S)

14. Concepts of the Nottinghamshire Adult Liver Disease Stratification pathway
Focussed on risk factors in addition to LFTS
Compromise between the views of the CCG, hepatology and NICE guidance
Stratification of liver risk rather than a definitive diagnostic test
Highlighting the need to link in with community services that deal with the underlying issues driving the risk factors including alcohol and weight loss

15. Acknowledging the following
Complex to follow !
The ICE interface is currently far from ideal and the need to take on feedback form users to improve this
Fatty Liver Index uses variables that may not be easy to access
( e.g. waist circumference and GGT)
The pathway is not didactic in some aspects – both an advantage and disadvantage
The pathway will be evaluated and iterated

16. Case 1 56 y/o female.Teacher
Only significant medical history was asthma
Hazardous alcohol intake for many years ( 30 units/week) but increase in last 18 months following work issues ( 50 units/week). Normal LFTs. BMI 30.
Monthly visits to GP with different symptoms over 9 months. Found to be hypertensive. Advised to reduce alcohol intake. Declined alcohol services. “Not an alcoholic”.
Invited to participate in the community study.

17. Case 1 Fibroscan reading elevated at 25 KpA
Review with hepatology and cirrhosis confirmed
OGD – showed early varices
Diagnosis was a “shock” ; cirrhosis was a diagnosis for people who “drank on park benches”.
Engaged with last orders, now abstinent for 2 years , off anti-hypertensive meds and has also lost 2 stones in weight.
Varices have disappeared on follow up endoscopy

19. Case 2 38 y/o shop assistant
History of anxiety – uses alcohol as anxiolytic (20 units per week)
Fluctuating weight with BMI of 30 to 35; borderline diabetes; raised cholesterol of 7
Strong FH of IHD and hyperlipidaemia
GP had offered statin but declined
ALT 67 but AST/ALT ratio normal
Referred to secondary care

20. Case 2 Liver screen performed in hospital – negative
U/S – shows significant steatosis .
FLI index consists of: BMI, waist circumference, Gamma GT and Triglyceride levels (pre current local guidance not calculated, but if it had been >60).
Fibroscan was 12 Kpa – indeterminate range
Petrified of liver biopsy – declined this. However the idea that she may have liver disease and this may stratify for future CV risk taken on board.
Lost 3 stones (via community weight loss services), referred for CBT and started statin
LFTS normal 12 months later and no evidence of insulin sensitivity

22. Case 3
MG 47 y/o security officer Type 2 diabetes , BMI 36 , teetotal Raised ALT fluctuating between 60 and 90 for 5 years AST/ALT ratio elevated 0.9. Liver screen not performed U/S – severe steatosis Declined referral. Assumed fatty liver

23. Case 3
Presented to hospital for episode of non specific chest pain. Abnormal LFTs noted and Liver screen requested – Hep B serology was positive (sAg and HBV DNA +ve) On further questioning – regular trips to Thailand with unprotected intercourse Treated with oral therapy ( HBV levels are undetected).

25. Case 4 52 y/o house wife Presents with “tired all the time” symptoms
Overweight BMI 30; Hypertension and hyperlipidaemia
Strong FH of type 2 DM
ALT 50, AST/ALT 0.9, ALP 456
Community U/S – shows steatosis, gall stones in GB.
Referred to secondary care

26. Case 4
Liver screen performed in hospital – positive Anti-mitochondrial Antibody and IgM raised
Liver biopsy – discussed and agreed.
Diagnosis of Primary Biliary Cholangitis (Stage 3 disease – Advanced fibrosis, not cirrhosis), some steatosis present.
LFTs normal after 12 months of Ursodeoxycholic acid.
Fatigue symptoms persist but participates in local PBC support group and has developed coping strategies.

28. Feedback:
e Healthscope Issues Log

29. The Scarred Liver Project Team
Guru Aithal
Dave Harman
Becky Harris
Neil Guha
Tim Card
Steve Ryder
Martin James
Emilie Wilkes
Aquiline Chivinge
AHSN
Nick Hamilton
Lucy Sitton-Kent
Primary Care
Matt Jelpke
Sean Ottey
Ken Brown
Marcia Chamberlain