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 zentonil@vetoquinol.co.uk and you will get a response from:

• Penny Watson MA VetMB CertVR DSAM DipECVIM MRCVS from Cambridge University