1. Dealing with NASH “mildly abnormal LFTs”

2. Liver disease is a national epidemic

4. Contribution of alcoholic liver disease to overall liver deaths

5. and a local disaster

7. Liverpool S.Tyne Knowsley Blackpool Manchester Wirral Gateshead Sunderland Sefton Newcastle Heywood Hartlepool Halton Blackburn Bolton Salford Oldham The North of England cluster has higher rates of Thiamine prescribing than the other SHA clusters

8. Are LFTs a useful test ?

9. How are LFTs ranges decided ► LFT values a continuum ► Abnormal are the extreme 2.5% ends ► “Normal” is shifting  8% of Americans have high LFTs (Clark AJG 2003) ► “Normal” may not represent “healthy”

10. Normal LFTs ► High “normal” LFTs assoc. with increased liver mortality (Kim BMJ 2004) ► 20% of HCV will have “normal” ALT (Kelly MJA 2002) (Kelly MJA 2002) ► 58% abn LFTs never investigated in primary care (Sherwood BMJ 2001) ALT RR liver death MF <201.01.0 20-292.93.8 30-399.56.6

11. How good are we at investigating abnormal LFTs ? ► Retrospective audit of primary care  Nottingham  Jan - Jun 1995 ► 342 consecutive abnormal LFTs ► 157 suitable for FU (not normalised, RIP or moved)  91 (58%)no further investigation  97 (62%) significant pathology

12. What are the commonest causes of LFT abnormalities

13. Causes of abnormal LFTs 42Alcoholic liver disease (23 with cirrhosis) 26Fatty liver / NASH (11 fibrotic on biopsy) 12PBC / AIH / PSC 6Haemochromatosis 2Hepatitis B 6Hepatitis C 3Common bile duct stones 1α1-antitrypsin deficiency 6Cryptogenic hepatitis (Sherwood BMJ 2001)

14. Basics of NASH ► NASH is common ► Most NASH is undetected  Untested  Normal LFTs ► NASH is “metabolic syndrome in the liver”  Associated with obesity / DM ► Most patients with NASH don’t die of liver disease

15. But ► Obesity / NASH potent cofactor for fibrosis ► NASH cirrhosis  Poor prognosis  High risk of HCC

16. Cumulative risk of HCC in 820,000 male veterans in hospital ’85-90 El-Serag 2004

17. Practical management ► Exclude other disease – aetiological screen  Diagnosis other than NASH  Other synergistic pathologies ► Assess severity ► Treat cofactors ► Weight and lifestyle management ► (Specific therapy)

18. Liver aetiological screen ► Hep B S-Ag ► Hep C antibodies ► Ferritin / Iron studies ► Autoantibodies ► Coeliac disease ► A1-AT ► Copper studies

19. Assessment of severity ► LFTs - virtually useless !!! ► FBC (platelets) ► US screen

20. Specific assessment ► Fibroscan ► Fibrotest ► Traffic lights ► Other indices

21. Southampton Traffic light test ► HA >30μg/l or P3NP >5.5μg/l+1 ► HA >75μg/l+2 ► Platelets <150+1 ► Score 0Green0% risk liver death 1Amber3% risk liver death 1Amber3% risk liver death 2+Red18% risk liver death 2+Red18% risk liver death

22. Management ► Refer if evidence of  Advanced fibrosis  Other disease ► Lifestyle advice  Weight  Diabetes  Alcohol ► Lipid R x ► Specific Rx

23. Thank you

24. ► NASH is 2-3% of population. ► 10-30% of NASH has the potential of developing into cirrhosis within 10 years. ► The emergence of significant fibrotic disease in developing countries, even in patients of normal weight or who are underweight is particularly concerning. ► More HCC in patients with Childs A undiagnosed NASH.