1. Liver Disease in the Older Patient

2. Agenda Liver Disease in the ageing patient Types Investigation Blood tests Others Treatment Antioxidants and Zentonil in Liver Disease Role Benefits of formulation Silybin

3. Types of Disease Affecting the Older Patient Inflammatory Chronic hepatitis (dogs) Lymphocytic hepatitis (cats) Infectious Leptospirosis Bacterial – Cholangiohepatits (cats) Toxic Drugs – NSAIDS (incl ibuprofen), steroids, paracetamol, carbimazole, phenobarbitone, azothioprine Metals – Copper, iron Vascular Acquired portal shunts

4. Types of Disease Affecting the Older Patient Metabolic Cushings disease Diabetes mellitus Hepatic lipidosis (cats) Neoplasia Primary Eg hepatic adenoma/carcinoma 26% tumours affecting liver in dogs, 20% in cats Haemolymphatic Eg lymphosarcoma, mast cell tumour 28% dogs, 60% cats Metastatic - 46% dogs, 20% cats Ideopathic

5. Investigation – Blood Tests Liver Enzymes ALT (AST, LDH) – hepatic leakage enzymes Released as a result of hepatocellular membrane damage Rise in serum concentration is proportional to hepatic insult Rarely, get decrease in end stage cirrhosis ALT pretty liver specific (some muscle) and short ½ life (cat-24h, dog-60h) AST and LDH poor liver specificity (heart and skeletal muscle) ALP, GGT – Induction enzymes Production induced by cholestasis No increase after liver injury (c.f. ALT) but many liver diseases cause cholestasis Mild increases significant in cats Cats do not have the steroid induced isoenzyme c.f. Dogs GGT maybe more sensitive for cholestasis in cat but less specific (intestine, kidney, pancreas)

6. Investigation – Blood Tests Bile acids Healthy liver good at extracting BA from portal circulation BAST more useful and is indicator of liver function Serum proteins Albumin synthesised by the liver Needs to be severe, prolonged liver disease to cause a decrease (long ½ life – 20d) Clotting factors Many synthesised by liver and many need Vit K which is decreased if cholestasis Important if considering liver biopsy CBC Anaemia Inflammation, infection

7. Investigation - Other Urinalysis Bilirubinuria – any is abnormal for cat Ammonia biurate crystals if PSS Ultrasound Radiography Liver biopsy

8. Treatment Diet Highly digestible, high quality protein (cottage cheese) Highly digestible carbohydrate Fibre – helps to trap ammonia Steroids Use if biopsy evidence of ongoing inflammation Not if ascites (portal hypertension) or extensive fibrosis Not if acute or infectious hepatitis Antibiotics To treat primary cause if infectious (cephalexin, FQs, metronidazole) Or secondary complication eg HE (ampicillin, amoxicillin) Avoid those that rely on hepatic clearance

9. Treatment Antifibrotic drugs eg Colchicine Consider if marked fibrosis Side effects common – anorexia (50%), bone marrow suppression Bile acid modifyers/choleretics Eg ursodeoxycholic acid (Destolit) Stimulates bile flow and displaces toxic bile acids Indicated in cholestatic liver dz (but not if complete obstruction) Antioxidants Eg S-adenosylmethionine and silybin

10. Zentonil®

11. The Role of Anti-oxidants in Liver Disease

12. Perfect SAMe product Pure stabilised SAMe Correct Isomer Protected from the harmful effects of stomach acid Palatable Divisible/Crushable Chewable Accurate dosing Bioavailability data SAMe stable in multipharmacy products Cost effective

13. Problem Enteric coating is required as digestion by stomach acid may reduce bioavailability. This means tablets cannot be split as coating is on the outside of the tablet The Solution is Zentonil® Advanced Patent pending microencapsulation technique that enterically coats tiny particles of SAMe, allowing tablets to be broken and chewed whilst protecting the SAMe molecules from the harmful effects of stomach acid

15. Problem SAMe must be given on an empty stomach and therefore manual administration (pilling) is required The Solution is New Zentonil® Proven palatability makes administration without food, and therefore ‘compliance’, easier

17. Problem Inability to split tablets due to enteric coating: makes administration expensive for certain weights of animal leads to a wide variation in SAMe levels received between different weights The Solution is New Zentonil® Advanced Divisible, scored tablets allowing Accurate tablet to weight administration which limits costs

18. Problem: Lack of data on bioavailabilty The New Zentonil® Advanced solution Proven bioavailability After oral administration of Zentonil®, SAMe is available for use by the body within 10 minutes of administration and peak levels are achieved between 1 to 4 hours after administration. The bioavailability curves were constant between test subjects SAMe should be given on an empty stomach for optimal effectiveness Feeding one hour after administration of Zentonil® allows optimal SAMe absorption and the levels will be at their highest to support the liver through the time when digestion is occurring

19. Zentonil® Advanced Zentonil® Advanced is a divisible, palatable formulation of SAMe with the additional benefits of silybin SAMe plus silybin

21. Zentonil® Advanced Silybin in Zentonil® Advanced is complexed with phosphatidylcholine. Oral bioavailability of silybin is very low but is significantly increased when complexed with phosphatidylcholine (PC). PC coats the silybin and makes it easier to be absorbed across the intestines By providing silybin in this form, bioavailability of silybin is up to 10 times higher than that achieved by giving silymarin.

22. Vetoquinol’s microencapsulation technique ensures optimal bioavailability of SAMe.

23. Administration When should I use Zentonil®? Zentonil® can be used in all cases when the liver is known or expected to require support in both dogs and cats Administration Tablets should be given on an empty stomach at least one hour before or two hours after feeding for optimal effectiveness

25. Administration

27. Ask the expert scheme Got a liver case and want advice from a specialist? Email zentonil@vetoquinol.co.uk and you will get a response from:zentonil@vetoquinol.co.uk Penny Watson MA VetMB CertVR DSAM DipECVIM MRCVS from Cambridge University