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Liver Disease in the Older Patient Agenda • Liver Disease in the ageing patient • Types • Investigation • Blood tests • Others • Treatment • Antioxidants and Zentonil in Liver Disease • Role • Benefits of formulation • Silybin 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 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 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) 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 Investigation - Other • Urinalysis • Bilirubinuria – any is abnormal for cat • Ammonia biurate crystals if PSS • Ultrasound • Radiography • Liver biopsy 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 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 Zentonil® The Role of Anti-oxidants in Liver Disease 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 • 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 • 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 • 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 • 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 Zentonil® Advanced • Zentonil® Advanced is a divisible, palatable formulation of SAMe with the additional benefits of silybin • SAMe plus silybin 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. • Vetoquinol’s microencapsulation technique ensures optimal bioavailability of SAMe. 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 Administration Ask the expert scheme • Got a liver case and want advice from a specialist? • Email [email protected] and you will get a response from: • Penny Watson MA VetMB CertVR DSAM DipECVIM MRCVS from Cambridge University